serological status of donor and recipient and degree of immunosuppression used are very important to assess risk of CMV disease. Valganciclovir is being used for both prophylaxis and treatment of CMV disease. Duration of prophylaxis also is dependent on serostatus- D+/R- 200 days, D-/R+ & D+/R+ 100 days, 200 days after ATG or Alemtuzumab and D-/R- No valganciclovir. Dose is 900 mg once daily but if renal impairment ten adjustment according to GFR. Routine monitoring is not needed during prophylaxis. Treatment is indicated if patient is symptomatic or as invasive CMV disease or CMV viral load is greater than 3 logs 10 or rising viral load. Different regimens available: Oral valganciclovir 900mg bd* for 21 days generally in cases where the viral load is >3log10 or have rising titer of CMV viral load and ganciclovir in cases with tissue invasive disease or viral load >4logs10.Dose of valganciclovir is 900mg bd* for 21 days , then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first. IV ganciclovir is administered in a dose of 5mg/kg twice a day for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. Dose adjustment is needed in case of renal impairment.Another regimen is 5mg/kg twice a day of IV ganciclovir for 14-21 days, and continued till 2 x PCR negative
The risk of the disease depend on the serological status of the donor and recipient and intensity of immunosuppression. Valganciclovir is licensed for prophylaxis and treatment of disease
The full prophylaxis dose is 900mg od according to renal profile and is provided for for
1.D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. any patient receiving intensified immunosuppression at any time point beyond 100
Surveillance and testing
Routine surveillance for viraemia is not required. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days started once they finish prophylaxis. CMV PCR on blood is the standard test.
Treatment is applied to
A. Patients that develop viraemia or disease whilst not on prophylaxis irrespective of viral load with reduction in immunosuppression if the viral load is fewer than 3 logs 10 and use valganciclovir if it exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10. IV ganciclovir is indicated in the presence of enteric absorption problem or severe organ involvement
B. Patients that develop viraemia or disease whilst on prophylaxis need consultant virologist decision.
Treatment options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Our local protocol is similar to these recommendations
Please summarise this protocol
Serological status of donor and recipient and degree of immunosuppression used are very important to assess risk of CMV disease. Valganciclovir is being used for both prophylaxis and treatment of CMV disease. Duration of prophylaxis also is dependent on serostatus- D+/R- 200 days, D-/R+ & D+/R+ 100 days, 200 days after ATG or Alemtuzumab and D-/R- No valganciclovir. Dose is 900 mg once daily but if renal impairment ten adjustment according to GFR. Routine monitoring is not needed during prophylaxis.
Treatment is indicated if patient is symptomatic or as invasive CMV disease or CMV viral load is greater than 3 logs 10 or rising viral load. Different regimens available: Oral valganciclovir 900mg bd* for 21 days generally in cases where the viral load is >3log10 or have rising titer of CMV viral load and ganciclovir in cases with tissue invasive disease or viral load >4logs10.Dose of valganciclovir is 900mg bd* for 21 days , then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first. IV ganciclovir is administered in a dose of 5mg/kg twice a day for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. Dose adjustment is needed in case of renal impairment.Another regimen is 5mg/kg twice a day of IV ganciclovir for 14-21 days, and continued till 2 x PCR negative. Please reflect on your practice
At our center, we follow the similar protocol , Valganciclovir is used in a mini prophylactic dose i.e., 450mg once daily in D+/R+ & D+/R-. and those receiving ATG induction,and continued for 3 months. Treatment is with ganciclovir in cases similar as mentioned above and VGC for mild moderate cases Treatment dose of valganciclovir at our center is 900mg twice a day for 21days or 2 x PCR-01 week apart negative followed by mini-prophylactic dose of VGC.IV ganciclovir is administered in a dose of 5mg/kg twice a day but adjusted according to GFR for 2-3 weeks or 2 x PCR-01 week apart negative.
Sheffield teaching hospital CMV protocol for prophylaxis and treatment of CMV in kidney transplant recipients: The main principals: · The donor (D) and recipient (R) serological state decide the risk of CMV disease · The immunosuppression (IS) strength will decide the risk of disease. · Valganciclovir (vGCV) is is used in both prophylaxis and disease treatment · (D+R-) group of patients continue to be at risk of CMV viraemia and CMV disease after the finish taking their .prophylaxis. CMV prophylaxis: · Those with (D+/R) will receive 200 days of valganciclovir 900mg OD. Doses are adjusted according to creatinine clearance. · The D+/R+ and D-/R+ groups will receive 100 days of valganciclovir, but extended to 200 days if they received T cell depleting agents (ATG or Alemtuzumab) · D-/R- require no prophylaxis Surveillance and testing by indication in suspected CMV viraemia or disease.
Routine surveillance for viraemia is not required during prophylaxis
The D+/R- should have their serostatus (CMV IgG) checked at or around 200 days and they should start surveillance after finishing their prophylaxis using with CMV PCR.
Extra clinic visits to check bloods may be required at 2,4,8 and weeks
The definitive test for diagnosis CMV viraemia or disease is to check CMV PCR in the blood. This is done in all suspected patients regardless on prophylaxis or not.
Thresholds for treatment A. Patients who have viraemia or disease while not on prophylaxis 1.Treatment should be started in all cases of suspected tissue-invasive CMV disease irrespective of viral load. 2. Immunosuppression doses are reduced in R+ patients who have a viral load < 3 logs 10. 3. vGCV treatment is advisable in high-risk group of patients with a viral load > 3 log 10 if they are symptomatic or have a fast rising viral titer. 4. Those with a viral load >4 logs 10, oral vGCV or IV GCV treatment is necessary. 5. IV GCV is advisable in cases when enteric absorption is compromised (diarrhea or vomiting). 6. IV GCV is the drug of choice whenever there is serious organ involvement .However, it is a consultant based decision.. B. Patients that develop viraemia or disease whilst on prophylaxis 1These cases should be discussed with the virologist to set up an optimal treatment plan, as well as to test for drug resistance Treatment: There are 3 choices: · Oral (vGCV) 900mg BD for 21 days, then 900mg OD for 28 days or until 2 negative PCR tests. · IV (GCV) 5mg/kg BD for 5 days followed by oral (vGCV) 900mg OD until 2 x PCR negative. · IV (GCV) 5mg/kg BD for 14-21 days, stop date determined by 2 x Pnegative. Doses of both drugs to be adjusted according to creatinine clearance Reflection on local practice: In NHS Grampian we are implementing Edinburgh renal transplantation unit protocol for CMV treatment: Alternatives include IV Ganciclovir or oral Valgancyclovir Individual decisions are taken based on the disease severity and viral load In general, IV Ganciclovir is started initially for 2 weeks followed by oral Valganciclovir and treatment is continued until 2 consecutive negative CMV PCR results are obtained within the same week. In mild asymptomatic cases or with low viral loads, oral Valganciclovir can substitute IV Ganciclovir Doses are adjusted according to creatinine clearance
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
· The serological status of the donor and recipient determines the risk of disease
· The intensity of immunosuppression determines the risk of disease.
· Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
· High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis. Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule: –
2 weeks –
4 weeks –
8 weeks –
12 weeks
The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised.
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis 1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing. Treatment The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease
. 3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
● D+/R- ==> 200 days of valganciclovir.
●D-/R+ and D+/R+ ==> 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
●D-/R- ==> No valganciclovir
●Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
●The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
■. Routine surveillance for viraemia is not required during prophylaxis
■ D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
■ D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
■CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3 Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients
. 4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10
. 5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
consultant virologist
Treatment
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first.
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
○Valganciclovir, at least 3 months, for high risk recipients.
Risk factors for CMV infection:
●D+/R-
●R+ receiving ATG or other intense ●immunosuppression treatment or the need of desensitization.
○ Valganciclovir children dose is adjusted depending on BSA.
○ CMV is a widespread virus. Its prevalence is about 100% in Asia compared to 80% in Europe and North America.
==> Only rare cases of R- we will encounter.
○There is no center in our country qualified to perform ABO incompatible renal transplantation.
==> We will not face the need of desensitization in except of pre-transplant blood transfusion and so on.
Treatment
□Ganciclovir 5mg/kg twice a day intravenously for 2- 3 weeks.
□ After 2 week, whole blood QNAT is performed weekly.
□ Treatment will be stopped after two negative QNAT.
□Dose should be adjusted depending eGFR.
◇without rejection ==>reduction of immunosuppression (especially in severe or unresponsive situation.
◇with rejection==> reduction of immunosuppression is challenging. Therefore, decision is made case by case
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at
any time point beyond 100 days
5. The full prophylaxis dose is adjusted according to renal function
*. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of
viral load.
There are three options:
1. Oral valganciclovir
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
CMV prophylaxis Valganciclovir for 100 or 200 days are prescribed in the following situations:
* Donor Positive or Donors of unknown serostatus to a negative recipients
* recipients positive receiving induction for fear of reactivation
* During a phase of transplant rejection in either positive donor or recipient
* in some centres they use it as a Prophylactic medication against other Herpes viruses
special considerations for Valganciclovir Prophylactic treatment: Renal adjustment of the dose is mandatory
* calculation of the dose according to body surface area
* in case of development of drug side effects , stopping the drug is required with continuous monitoring of CMV level and preemptive management
Active treatment of CMV used in the following situations :
* Tissue invasive CMV
* Viral load more than four log
* Titres rapidly rising in high risk patients especially Donor positive recipient negative patients more than three logs
Oral Valganciclovir 900 mg twice daily for three weeks followed by a once daily 900 mg Valganciclovir for four weeks or until we have two successive negative PCR
An Alternative approach I.V Gangiclovir 5 mg/kg twice daily followed by Valganciclovir oral 900 mg once daily until two negative PCR sample
an alternative approach I.V Ganciclovir 5 mg per kilogram for two to three weeks until 2 negative PCR samples .take In consideration the same precautions in dose as in the Prophylactic treatment.
•Consider stopping or at least Reduction of 50 % of dose of MMF
•50 % Reduction of CNI or shift to mTOR. Reconsider readjusting immunosuppression after cleaning CMV
Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed. Surveillance and testing by indication in suspected CMV viraemia or disease
1. No surveillance for viraemia during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4- Blood CMV PCR on blood is the standard test. Thresholds for treatment :
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10
3- Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement.
If the patients develop viraemia or disease whilst on prophylaxis :
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing Treatment
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Please summarize this protocol: CMV prophylaxis depends on CMV serology of the donor and recipient, and the immunosuppression. D-/R-: no need. D+/R-: 200 days of Valganciclovir. D-/R+ and D+/R+: 100days of valganciclovir and 200 days after ATG or Alemtuzumab. Patients receiving intensified IS at any point after the first 100 days, such as after receiving heavy IS for acute rejection. Surveillance of CMV: 1- CMV PCR in blood.
2-D+/R- recipients should have their CMV IgG checked at 200 days.
3-D+/R- recipients should start surveillance once they finish prophylaxis.
Treatment thresholds:
1-patients who develop CMV vireamia or CMV disease if they are not on prophylaxis.
2-all cases with tissue invasive CMV disease should be treated.
3-Reduce immune-suppression in R+ with viral load less than 3 logs 10.
4-Use valganciclovir for CMV treatment if CMV viral load above 3 logs 10 if patients are symptomatic or rapidly rising CMV titer.
4-If CMV viral load above 4 logs 10, use IV Ganciclovir or oral valganciclovir.
5-Use IV Ganciclovir in case of severe organ involvement.
6-Regimens available:
A- Oral Val ganciclovir 900mg BD for 3 weeks, then 900mg OD for 4 weeks or until 2 x PCR negative.
B- IV ganciclovir 5mg/kg BD for 5 days followed by oral Val ganciclovir 900mg OD until 2 x PCR negative.
IV ganciclovir 5mg/kg OD for 2-3 weeks, stop date determined by 2 x PCR negative.
Protocol for prophylaxis, surveillance and treatment of CMV after renal transplantation
Principles
The serological status of the donor and recipient determines the risk of disease.
The intensity of immunosuppression determines the risk of disease.
Valganciclovir is licensed for prophylaxis but is often also used for treatment.
High risk patients (D+R-) remain at risk of CMV viremia and disease after they complete the prophylaxis.
Prophylaxis
Prophylaxis should be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days.
The full prophylaxis dose is 900 mg od but there is dose adjustment if there is renal impairment.
D+/R- ; 200 days of valganciclovir.
D-/R+ or D+/R+ ; 100 days of valganciclovir, 200 day after ATG or Alemtuzumab.
D- /R- no valganciclovir
Surveillance and testing by indication in suspected CMV viremia or disease
1.Routine surveillance is not required during prophylaxis.
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viremia or disease is suspected,irrespective on prophylaxis or noyb
Threshold for treatment
1. patients that develop viremia or disease whilst not on prophylaxis
Treatment is mandatory in suspected tissue invasive CMV disease, irrespective of viral load.
Consider reduction in immunosuppression in R+ with a viral load of fewer than 3 log 10
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titer in high risk patients
Consider treatment if the viral load exceeds 4 logs 10
IV Ganciclovir is indicated where enteric absorption is likely to be compromised
IV Ganciclovir is indicated in any patient with severe organ involvement.
2. Patients that develop viremia or disease whilst on prophylaxis
Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment
the choice of oral versus IV therapy is determined by the above mentioned threshold
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation Principles
. Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed:
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days 3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
as per the following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 weeks
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) .
B. Patients that develop viraemia or disease on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Our institute protocol–
Since almost ( > 90%) all of our transplant are D+R+, we give prophylaxis for 3 month oral valganciclovi,Dose – 450 mg to all ,.and follow with Blood PCR monthly
Treatment-we give oral valganciclovir,usual dose is 450 bd for 21 days unless He/she have severe graft dysfunction –we dont give secondry prophlaxis. We generally reduce dose of immunosuppression by 50%(MMF) and follow with PCR
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the
prophylaxis.
Prophylaxis
200daysofvalganciclovir. 100daysofvalganciclovir,200daysafterATGorAlemtuzumab Novalganciclovir
1. D+/R-
2. D-/R+andD+/R+
3. D-/R-
4. Prophylaxisshouldalsobeconsideredforanypatientreceivingintensifiedimmunosuppressionat
any time point beyond 100 days – Consultant decision.
5. Thefullprophylaxisdoseis900mgodbutnotethatdosereductionforrenalimpairmentis
commonly needed: please consult the Renal Drug Handbook or pharmacist for the appropriate regime and revise in the event of changing renal function.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Page 2 of 3
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g., pneumonitis, encephalitis) – Consultant decision.
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R- ==> 200 days of valganciclovir.
2. D-/R+ and D+/R+ ==>100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use). i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy; please consult the Renal Drug Handbook or pharmacist for an appropriate regime and revise in the event of changing renal function.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases. Additional therapy may be appropriate following the discussion.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles :
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed: please consult the Renal Drug Handbook or pharmacist for the appropriate regime and revise in the event of changing renal function.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days 3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
2 weeks
4 weeks
8 weeks
12 weeks
The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10. Page 3 of 3
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy; please consult the Renal Drug Handbook or pharmacist for an appropriate regime and revise in the event of changing renal function.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases. Additional therapy may be appropriate following the discussion.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the
prophylaxis. Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at
any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is
commonly needed. Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
As per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease
is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or
not. Thresholds for treatment A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of
viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI
involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis,
encephalitis) – Consultant decision. B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss
resistance testing Treatment
The choice of oral versus IV therapy is determined by the above mentioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,
whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and
ganciclovir therapy.
reflect on yourpractice.
we follow the almost same protocol.
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at
any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly
needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment:
A. Patients that develop viraemia or disease whilst not on prophylaxis.
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease , irrespective of
viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI
involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis,
encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis:
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss
resistance testing
Treatment:
The choice of oral versus IV therapy is determined by the above mentioned thresholds and criteria.
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases.
2- Please reflect on your practice:
In our center
1- Risk is determined according sero -status of donor and recipient .
2- Prophylaxis is usually used for 3 months .
3- Serostatus is not checked after completion of prophylaxis course .
4- Q NAT used to diagnose CMV disease.
5- Viral load as a threshold for treatment is not used.
6- Iv gancyclovir or valgancyclovir is used for treatment .
This protocol stated how to prevent, surveillance & treatment of CMV following renal transplantation.
Prophylaxis
Depends on serological status of donor & recipient and intensified immunosuppression.
Preferable drug : valganciclovir 900mg once daily.
1. D+/R- : 200 days following transplantation
2. D-/R+ and D+/R+ : 100 days following transplantation
3. D+/R- : no prophylaxis
4. Intensified immunosuppression during acute rejection at any poin: 100 days.
Surveillance following prophylaxis
D+/R- patient should check CMV IgG at or around 200 days and start surveillance with CMV PCR afer finishing prophylaxis as per following shedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
Threshold for treatment
Treatment is mandatory in tissue- invasive CMV disease
Viral load of fewer than 3 logs 10: appropriate reduction in immunosuppression.
Viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high- risk patient: Treatment with valganciclovir or IV ganciclovir.
Compromise enteric absorption or severe organ involvement(pneumonitis, encephalitis)- IV ganciclovir
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation:
Prophylaxis:
1. D+/R- 200 days of Valganciclovir.
2. D-/R+ and D+/R+ 100 days of Valganciclovir, 200 days after ATG or Alemtuzumab.
3. D-/R- No Valganciclovir.
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viremia or disease:
1. Routine surveillance for viremia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
Following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 week.
4. CMV PCR on blood is the standard test.
Thresholds for treatment:
A. Patients that develop viremia or disease whilst not on prophylaxis:
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease,
irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with Valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titer in high-risk patients.
4. Treatment with Valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be .
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viremia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment.
Drugs treatment:
There are three options:
1. Oral Valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral Valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice:
We are treating CMV disease with ganciclovir. and valganciclovir for prophylaxis of D+/R- patient.
This is a protocol for prophylaxis surveillance and treatment of CMV post kidney transplantation.
Principles
Disease risk is dependent on serological status of both donor and recipient, and the intensity of immunosuppression that is given to the recipient.The drug that is used is valganciclovir. It can be used for both prophylaxis as well as for treatment.The recipient remains at risk of CMV disease even after completing prophylactic treatment, which means that prophylaxis with valganciclovir does not confer unconditional protection to the patient.Prophylaxis
If the donor is positive and recipient negative, then 200 days of valganciclovir.If the donor is negative and recipient is positive, or if both donor and recipient are positive, then 100 days of valganciclovir for former, and 200 days after ATg or alemtuzumab for the latter case.If both donor and recipient are seronegative, then there is no need for valganciclovir.If the patient is receiving IS for more than 100 days, then prophylaxis must be considered irrespective of the serology.Dosage for full prophylaxis is 900 mg OD but dose reduction may be needed depending on kidney function status.Surveillance
Routine surveillance is not required.CMV IgG should be checked at 200 days and once both donor and recipient are finished with prophylaxis.CMV PCR is to be done irrespective of prophylaxis.Treatment thresholds
Treatment is mandatory in all cases of suspicion irrespective of viral load.Reduction in IS is to be considered in seropositive recipients.If patient cannot take oral valganciclovir due to GI involvement, vomiting or diarrhea, then IV valganciclovir is to be given.Treatment
Three options are available :
Oral valganciclovir 900 mg bd for 21 days then 900 mg od for 28 days or until 2 x PCR negative, whichever is first.IV ganciclovir 5 mg/kg bd for 5 days followed by oral valganciclovir 900 mg od until 2x PCR negativeIV ganciclovir 5 mg/kg bd for 14-21 days until 2 x PCR negative. Practice
Prophylaxis with ganciclovir is done for 100 days in high risk patients such as those donor positive and recipient negative.
Treatment with ganciclovir is done oral for 6 weeks followed by PCR test.
1. Please summarize this protocol Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation at Sheffield Teaching Hospital (NHS) Date: July 2016 (3rd revision) Review Date: July 2019 Sheffield Kidney Institute Clinical Governance Meeting Date: 18th August 201 Principles 1. Determinant of Risk of CMV infection and disease
o Sero-status of the donor and recipient
o Intensity of immunosuppression 3. Valganciclovir is licensed for prophylaxis, but is also used for treatment of CMV disease. 4. (D+R-) recipients remain at risk of CMV viraemia and disease, even after completion of prophylaxis
Prophylaxis: (Valgancyclovir 900mg OD PO; dose modified as per GFR) D+/R- given 200 days D-/R+ and D+/R+ à given 100 days D-/R+ and D+/R+ receiving ATG / Alemtuzumab induction à 200 days.
D-/R- no prophylaxes.
Surveillance and testing in suspected CMV Viremia or Disease: 1. No Routine surveillance for viraemia during prophylaxis 2. D+/R- patients after completion of 200 days prophylaxis
o To Check serum CMV IgG
o surveillance with CMV PCR at 2 weeks, and monthly for 3months (2-4-8-12weeks) 3. CMV PCR on blood for suspected CMV disease irrespective of being on prophylaxis
Treatment: Thresholds to decide treatment and regimen A. CMV viraemia or disease (not on prophylaxis) 1.All cases of tissue-invasive CMV disease 2. Immunosuppression reduction 3. Consider treatment for Symptomatic patients with viremia >3 logs10 or rapidly rising titre – Treatment is mandatory if viral load exceeds 4 logs 10. 4. IV ganciclovir is indicated if GI involvement (Gastritis, colitis), diarrhoea or vomiting. 5. IV ganciclovir if severe organ involvement (pneumonitis, encephalitis)
Treatment regimen: Mild cases –
Ø Oral Valganciclovir 900mg bd x 21 days à then 900mg od x 28 days or until 2 x PCR negative
If IV therapy indicated, as per above threshold –
Ø IV ganciclovir 5mg/kg bd x 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
Ø In seriously ill patients: IV ganciclovir 5mg/kg bd x 14-21 days, stop date determined by 2 x PCR negative.
B. Viraemia or CMV disease even on prophylaxis
Ø Treatment with appropriate regimen as per above threshold
Ø Discuss with virologist for best regime and resistance testing
2. Please reflect on your practice: v We use Valgancyclovir prophylaxes for 8 weeks in all our recipients (Low dose ATG induction 60%, Basiliximab in 40%) v We don’t have surveillance protocol. v We hardly see any symptomatic CMV disease
This is a protocol for prophylaxes, surveillance, and treatment for CMV at NHS. Prophylaxes; If D+/R- 200 days valgnciclovir prophylaxes. If D-/R+ and D+/R+ 100 days valganciclovir, if a patient given ATG or Alemtuzumab given 200 days. D-/R- no prophylaxes. Surveillance and testing by indication in suspected CMV viremia or Disease; For prophylaxes doesnot need monitoring. For D+/R- patients should be tested for CMV IgG at 200 days. For D+/R+ patients needed to monitor CMV PCR after 100 days and then at 2, 4, 8 and 12 weeks. Treatment; Treatment is mandatory for all suspected cases with symptoms irrespective of viral load. Immunosuppression modification accordingly. Consider with initiating valganciclovir when viral load >3 log and if symptomatic and rapidly raising titers. Consider IV genciclovir when there is compromised absorption, CMV syndrome, already on prophylaxes but developed viremia. When the choice of treatment if oral valaganciclovir 900mg BD for 21 days, than 900mg OD for next 21 days or until two PCR negative. If IV ganciclovir 5mg/kg BD for 5 dys then switch to oral valganciclovir 900mg OD until two PCR negative or, IV ganciclovir 5mg/kg BD for 14 to 21 days/ until 2 PCR negative. 2. Please reflect on your practice; We use prophylaxes for 100 days in every patients because we have 100% positive patients. We don’t have surveillance protocol. We usually treat all patients with disease, syndrome with IV ganciclovir for 21 days, however, if CMV syndrome we continue valganciclovir oral next 100 days without surveillance.
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 weeks
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use)
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
1.D+/R- 200 days of valganciclovir. 2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab 3.D-/R- No valganciclovir 4.Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
The full prophylaxis dose is 900 mg od but note that dose reduction for renal impairment is commonly needed: please consult the Renal Drug Handbook or pharmacist for the appropriate regime and revise in the event of changing renal function.
Surveillance and testing by indication in suspected CMV viraemia or disease
1.Routine surveillance for viraemia is not required during prophylaxis 2.D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days 3.D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
– 2 weeks – 4 weeks- 8 weeks – 12 weeks The recipient team will coordinate this.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4.Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs10.
5.IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis,encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1.Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing Treatment The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.
There are three options:
1.Oral valganciclovir 900 mg bd* for 21 days, then 900 mg od* for 28 days or until 2 x PCR negative,whichever occurs first (off-label drug use).i 2.IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900 mg od* until 2 x PCRnegative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Note that dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy; please consult the Renal Drug Handbook or pharmacist for an appropriate regime and revise in the event of changing renal function.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases.
Additional therapy may be appropriate following the discussion
Please reflect on your practice
-In our practice we used extended prophylaxis 200 days for high risk patients( who receive ATG or D+/R- ). -Treatment is the same as your hospital protocol. -We didn’t encounter any Ganciclovir resistant cases
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Prophylaxis:
1. D+/R- 200 days of Valganciclovir.
2. D-/R+ and D+/R+ 100 days of Valganciclovir, 200 days after ATG or Alemtuzumab.
3. D-/R- No Valganciclovir.
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viremia or disease:
1. Routine surveillance for viremia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
Following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 week.
4. CMV PCR on blood is the standard test.
Thresholds for treatment:
A. Patients that develop viremia or disease whilst not on prophylaxis:
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease,
irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with Valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titer in high-risk patients.
4. Treatment with Valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be .
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viremia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment.
Drugs treatment:
There are three options:
1. Oral Valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral Valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice
We are treating CMV disease with ganciclovir. and valganciclovir for prophylaxis of D+/R- patient.
Prophylaxis
If donor is + and recipient is – prophylaxis will continue for 200 days.
D+\R- or D+\R+ 100 days of valganciclovir
200 days if AaTG or Alemtuzumab is used
No prophylaxis for D-/R-
Prophylaxis should also be considered for any parient given intensified immunosupression even beyond 100 days
CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Surveillance should be done for positive donors and negative recipients once they finish 100 days of prophylaxis.
Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
Treatment options
Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Our Center Protocol
since our all patients are D+\R+ we give them all valganciclovir 450 mg once daily for three months.
out treatment strategy is same like ur hospital
The Sheffield Teaching Hospitals NHS protocol for cytomegalovirus (CMV) post-kidney transplant includes:
1) Prophylaxis: Oral Valganciclovir 900 mg daily (to be adjusted according to creatinine clearance) should be given as prophylaxis for 200 days in D+/R- patients or those who receive ATG or Alemtuzumab, and for 100 days in recipients with a positive serology (D+/R+ or D-/R+). Any patient receiving intensive immunosuppression should be given prophylaxis as per consultant decision.
2) Surveillance: CMV IgG of D+/R- patients should be checked at 200 days post-transplant. Blood CMV PCR should be checked post completion of prophylaxis at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. It should also be done whenever CMV viremia or disease is suspected.
3) Treatment: Treatment should be given in tissue invasive CMV disease, when the viral load is >4 logs 10,rapidly rising titres in high-risk patient (D+/R-), or symptomatic patient with viral loa > 3logs 10. Treatment includes either oral salganciclovir 900 mg BD for 3 weeks, then 900 mg OD for 4 weeks, or until 2 negative blood CMV PCR reports; Intravenous ganciclovir 5 mg/kg BD for 5 days followed by oral valganciclovir 900 mg OD until 2 negative blood CMV PCR reports; or Intravenous ganciclovir 5 mg/kg BD for 2-3 weeks until 2 negative blood CMV PCR reports. Doses need to be adjusted according to the renal function.
2. Please reflect on your practice
In our transplant unit, we use oral valganciclovir as CMV prophylaxis as per the risk category of the recipient.
D+/R- patients are given prophylaxis for 200 days.
D+/R+ patients are given prophylaxis for 100 days.
Patients receiving ATG as induction are given prophylaxis for 100 days.
No surveillance with serology or CMV PCR is done in our unit.
CMV, once diagnosed, is treated with Injection Ganciclovir, till 2 negative CMV PCR reports, at least one week apart.
Summary: Principles: · Disease risk is determined by donor and recipient serology as well as intensity of immunosuppression. · Valganciclovir is used for prevention as well as treatment. · High-risk individuals (D+R-) remain at risk of CMV viremia and disease despite prophylaxis.
Prophylaxis: · If D+/R- 200 days valganciclovir prophylaxis. · If there is D-/R+ and D+/R+ 100 days valganciclovir, 200 days following ATG or Alemtuzumab. · D- /R- No prophylaxis. · Consultants should consider prophylaxis for patients receiving increased immunosuppression beyond 100 days. · The complete prophylaxis dosage is 900mg OD; however, renal impairment requires dose reduction.
Surveillance and testing: · Prophylaxis does not need viremia monitoring. · D+/R- patients should be tested for CMV IgG at 200 days. · D+/R- patients should start CMV PCR monitoring after prophylaxis and then after 2,4,8,12 weeks
Treatment : · Oral valganciclovir 900mg twice daily for 3 weeks, then 900mg once daily for 4 weeks or until 2 consecutive negative PCR tests whichever is shorter. · IV ganciclovir 5mg/kg twice daily for 5 days followed by oral valganciclovir 900mg once daily until 2 consecutive negative PCR tests. · IV ganciclovir 5mg/kg twice daily for 2-3 weeks and stop if 2 consecutive negative PCR tests. · Dose reduction is needed in compromised renal function.
Please reflect on your practice : · In our setting all recipients get Valganciclovir prophylaxis (3-6 months) except D-/ R-, which we have not experienced yet.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantationPrinciples 1. The disease risk is determined by the serological status of the donor & recipient and The intensity of IS.
2. Valganciclovir is licensed for prophylaxis and often in treatment of disease.
3. High-risk patients (D+/R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis. Prophylaxis 1. D+/R- (200 days of valganciclovir).
2. D-/R+ and D+/R+ (100 days of valganciclovir, 200 days after ATG or Alemtuzumab).
3. D-/R- (No valganciclovir).
4. Prophylaxis should also be considered for any patient receiving intensified IS at
any time point beyond 100 days (Consultant decision).
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed. Surveillance and testing by indication in suspected CMV viraemia or disease 1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. 4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not. Thresholds for treatment A. Patients that develop viraemia or disease whilst not on prophylaxis 1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load. 2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10. 3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised 6. IV ganciclovir is indicated in any patient with severe organ involvement. B. Patients that develop viraemia or disease whilst on prophylaxis 1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing Treatment The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options: 1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use). 2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
Sheffield Kidney Institute CMV protocol (review date 2016)
*** Prophylaxis Valganciclovir 900 mg od is considered for any +ve D/R CMV between 100-200 days (longer for +/- and severe immunosuppressed) D-/R- does not require
*** Surveillance start after finished the antiviral prophylaxis with monitoring CMV PCR on blood after 2-4-8-12 weeks
*** TreatmentIf a patient develops positive CMV on surveillance, assesses clinically for any symptoms and looks for tissue-invasive CMV disease.
Log < 3:Reduce immunosuppression Log 3-4: Consider treatment with valganciclovir if symptomatic or rapidly rising titre in high-risk patients Log > 4: ttt with valganciclovir
IV ganciclovir indicated for:
enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
Any patient with severe organ involvement (e.g. pneumonitis, encephalitis)
Regimens: 1. Oral valganciclovir 900mg bd for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use) 2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Reflection:
nice and clear protocol but I wonder if it needs to be reviewed after the guidelines we had earlier. In practice, I have not exposed to acute transplant yet in my centre
Summary:
· Serological typing by CMV IgG prior to transplantation is essential for risk stratification.
· High risk D+/R-, intermediate risk when R is +ve whatever donor serological status , and low risk when both are negative.
· Prophylaxis by oral valganciclovir differs according to the risk:
o 200 days for high risk.
o 100 days for intermediate risk.
o No prophylaxis in low risk
· Surveillance for CMV viremia: is indicated after the end of 200 days of universal prophylaxis in high risk D+/R-.This surveillance is by CMV PCR in the blood.
· Ttt is indiacted in any conformed tissue invasive disease irrespective to the viral load, and if the viral load is > 5 log 10.
· Ttt can be considered in rising titre of PCR or more than 3 log10 with symptoms.
· IV ganciclovir, rather than oral valganciclovr is indicated in children, severe diases, presence of diarrhea and fear of oral absorption.
· Renal adjustment of the dose according to the GFR is essential.
PROTOCOL FOR CMV PROPHYLAXIS,SURVEILLANCE AND TX POST RENAL TRANSPLANT.
PROPHYLAXIS
1.Donor +VE/Recipient -VE – 200/7 of valganciclovir.
2.Donor -VE/Recipient +VE & Donor +VE/Recipient +VE -100/7 of valganciclovir,200/7 after ATG or Alemtuzumab.
3.Donor -VE/Recipient -ve -No prophylaxis.
4.Any immunosuppressive meds anytime beyond 100/7 is an indication for prophylaxis.
5.Prophylaxis ; 900mg OD, renal dose appropriately esp eGFR <60ml/min.
SURVEILLANCE AND TESTING IN SUSPECTED CMV INFECTION OR DX.
1.During prophylaxis, there’s is no indication for surveillance.
2.D+/R- pts should have CMV IgG done at~200/7.
3.D+/R- pts should be surveilled with CMV PCR after completion of prophylaxis at ~ 2/52,4/52,8/52 and 12/52
4.Whenever CMV infection or dx is suspected do CMV PCR.
THRESHOLDS FOR TX.
A. Pts who get CMV infection with no prophylaxis.
1.Tx indicated in all tx invasive dx irrespective of VL.
2.RIS in R+VE with VL > 3 logs 10.
3.Tx with valganciclovir if VL >3 logs 10 if symptomatic or increasing VL.
4.Tx with valganciclovir or IV ganciclovir if VL > 4 logs 10.
5.In invasive dx with impaired absorption ,give IV ganciclovir.
6.Severe dx with organ involvement e.g pneumonitis or encephalitis is an indication for parenteral tx.
B.Pts that dev infection or dx while on prophylaxis.
1.Consult a virologist ,start tx and consider resistance testing.
TREATMENT.
Options;
1.PO Valganciclovir 900mg BD -21/7 Then 900g OD -28/7 or until x2 negative PCR.
2,IV Ganciclovir 5mg/kg BD -5/7 then PO valganciclovir 900mg OD until x 2 negative PCR.
3.IV Ganciclovir 5mg/kg BD -14-21/7 ,until x2 Negative PCR.
REFLECTION ON PRACTICE;
Lack of funds and resources limits implementation of the protocol in our center.
-For those with dx, we always give PO valganciclovir 900mg BD -21/7 then Maintain at 900mg OD X 3/12
-We don’t routinely give prophylaxis following high dose immunosuppression treatment for rejection.
-Due to again lack of resources, we hardly transplant D+/R- pairs and only consider prophylaxis after ATG tx for rejection.
III. Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation – Sheffield Teaching Hospitals Protocol
Summarise this protocol
Principles
– The donor: recipient CMV serostatus determines the risk of disease.
– The intensity of immunosuppression also determines the risk of CMV disease.
– Valganciclovir is used as prophylaxis as well as treatment of CMV disease
– High-risk patients i.e., (D+/R-) remain at increased risk of CMV viremia and disease even after completing valganciclovir prophylaxis.
Prophylaxis
(D+/ R-) give 200days of valganciclovir
(D-/ R+) and D+/ R+ give 100days of valganciclovir or 200days after ATG or alemtuzumab
(D-/ R-) no role for valganciclovir
Prophylaxis should be considered in patients receiving intensified immunosuppressive therapy at any one point beyond 100days
Prophylactic dose is 900mg OD but she be adjusted according to the kidney function
Surveillance and testing by indication in suspected CMV viremia or disease
– There is no role for routine surveillance for viremia during prophylaxis.
– (D+/ R-) patients should have their CMV IgG status checked at/ or around 200days.
– (D+/ R-) patients should start surveillance with CMV PCR once they finish their prophylactic dose at 2, 4, 8 and 12 weeks.
– The standard test for all transplant recipients is CMV PCR on blood irrespective of whether the patient is on prophylaxis or not.
Thresholds for treatment
Patients who develop viremia or disease whilst not on prophylaxis
– All cases of suspected tissue-invasive CMV disease irrespective of CMV viral load should be initiated on treatment.
– Consider judicious reduction in immunosuppressive therapy in R+ patients with a CMV viral load of less than 3 logs 10.
– Consider initiating treatment with valganciclovir if the CMV viral load is greater than 3 logs 10, if patient is symptomatic or if the CMV viral load titers rise rapidly in high-risk patients.
– When the CMV viral load exceeds 4 logs 10 initiate treatment with valganciclovir or IV ganciclovir.
– In cases where enteric absorption of valganciclovir is compromised (e.g., due to proven GI involvement, vomiting, diarrhoea), IV ganciclovir should be given
– Patients with severe organ involvement e.g., encephalitis, pneumonitis should get IV ganciclovir
Patients who develop viremia or disease whilst on prophylaxis
– Discuss with the virologist and decide on the appropriate treatment regime as well as discuss resistance testing.
Treatment – three options exist i.e.,
– Oral valganciclovir 900mg BD for 21 days then 900mg OD for 28 days or until the patient attains 2 negative CMV PCR tests whichever comes first
– IV ganciclovir 5mg/kg BD for 5 days then oral valganciclovir 900m OD until the patient obtains 2 negative CMV PCR tests
– IV ganciclovir 5mg/kg BD for 14-21 days, the stop date is dependent on obtaining 2 negative CMV PCR tests
– All ganciclovir and valganciclovir doses should be adjusted as per kidney function
Reflect on your practice
– At our transplant center, we screen for CMV serostatus and risk stratify the donor and recipient.
– We do not routinely offer valganciclovir prophylaxis unless the recipient has received ATG which is also not a common occurrence.
– We also do not offer prophylaxis following intensified immunosuppressive therapy e.g., after rejection.
– Our main drawback is financial constraints – valganciclovir is not affordable to most of our patients neither is routine CMV viral load monitoring
– For patients who have a confirmed diagnosis of CMV disease, we usually give oral valganciclovir 900mg BD for 3 weeks then 900mg OD as secondary prophylaxis for about 3 months.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Serological status of the donor and recipient determines the risk of disease. Intensity of immunosuppression determines the risk of disease.
High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis:
D+/R- 200 days of valganciclovir 900mg OD depending renal function
D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
D-/R- No need prophylaxis
Surveillance and testing by indication in suspected CMV viraemia or disease:
Routine surveillance for viraemia is not required during prophylaxis
D+/R- should have their serostatus (CMV IgG) checked at or around 200 days
D+/R- should start surveillance with CMV PCR once finish prophylaxis
Thresholds for treatment:
Patients that develop viraemia or disease whilst not on prophylaxis
Treatment is mandatory in all cases of suspected tissue invasive CMV disease, irrespective of viral load.
Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs10.
IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea, or vomiting).
IV ganciclovir is indicated in any patient with severe organ involvement (e.g., pneumonitis, encephalitis) – Consultant decision. Treatment:
There are three options:
Oral valganciclovir 900mg bd for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use)
IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od* until 2 x CMV PCR negative.
IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative. The dose needs renal adjustment in reduced kidney function (CrCL) In my Practice:
Pre-transplant workup Screening CMV (IgG antibody) for both donors and recipients is considered in our protocol and everywhere.
Prophylaxis is recommended for recipients who received ATG induction or received ATG for Acute Cellular Rejection for six months.
OR when the donor recipient sero- status MM is (D+/ R-) CMV IgG => six months.
Prophylaxis for CMV (D-/R-) with Basiliximab => No prophylaxis needed.
Prophylaxis for CMV (D-/R-) with ATG => six months prophylaxis needed.
Prophylaxis for CMV (D+/R+) with Basiliximab => No prophylaxis needed.
Prophylaxis for CMV (D+/R+) with ATG => six months prophylaxis needed. Valganciclovir prophylaxis for 6 months following treatment of ACR ttt by ATG. Dose Adjusted according to Cr CL .
Sheffield teaching hospitals protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation.
Principles of risk assessment
Serological status of donor and recipient
degree of immunosuppression
Seropositive donor/seronegative recipient are at risk of CMV viremia and disease after prophylaxis.
Prophylaxis
Offer valganciclovir for 200 days in D+/R-.
Offer valganciclovir for 100 days in D-/R+ and D+/R+,
Offer valganciclovir for 200 days after ATG or Alemtuzumab
No prophylaxis for D-/R-
Consider prophylaxis for any patient receiving intensive immunosuppression at any time point beyond 100 days but inform the consultant before the decision.
The full prophylaxis dose is 900mg od but adjust for renal impairment. Consult the Renal Drug Handbook or pharmacist for the appropriate dosing in the event of a changing renal profile.
Surveillance and testing by indication in suspected CMV viraemia or disease.
No need for a routine surveillance during prophylaxis.
D+/R- patients should have their serum CMV IgG checked around the time of completion of prophylaxis.
D+/R- patients should start monitoring with CMV PCR once they complete prophylaxis. This may be every schedule at the following intervals or more frequently if needed at: – 2 weeks – 4 weeks – 8 weeks – 12 weeks coordinated by the recipient team.
CMV PCR on blood is the standard test for all categories of transplant recipients for diagnosis of CMV infection or disease.
Thresholds for treatment
In recipients that develop CMV syndrome or disease whilst not on prophylaxis
1. Treat all suspected tissue invasive CMV disease irrespective of viral load.
2. Consider a reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 with symptomatic infection or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where intestinal absorption is likely to be inadequate (e.g. proven GI disease, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) after discussing with the consultant.
In recipients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment option vis a vis drug resistance testing.
Treatment
Using either oral or IV therapy will be determined by the above thresholds and criteria.
There are three options:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever comes first
2. I V ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 negative PCR test.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stoppage to be determined by 2 negative PCR.
In reflecting on my practice;
Serologic testing using PCR to detect CMV IgG for donor and recipient.
Universal prophylaxis irrespective of serologic tatus for 6 months.
I have never had to treat CMV syndrome or infection before and we do not monitor for infection.
Please summarise this protocol
CMV prophylaxis Vs treatment assessed based on donor/ recipient serology,immunosuppresion protocol, CMV PCR and clinical presentation
Regarding serology
D+/R- considered as high risk needs treatment for 5-7 days then prophylaxis fro 200 days then close monitoring
D+/R+ and patient received depleting induction considered as low to moderate risk and need prophylaxis for 100 days followed by close CMV screening
D-/R- considered as low risk and need close CMV screening
Regarding CMV PCR log and clinical presentation
patient with tissue invasion even with negative serology is indicated for treatment either by gancyclovir or valgancyclovir based on consultant decision especially no risk of disturbed GIT absorption
less than 3 log needs immunosuppresion modification if possible
3 logs needs valgancyclovir treatment if symptomatic
4log needs valgancyclovir irrespective to presentation
In my transplant center we used to divide cases into
1. High risk patients (D+ to R-): for such patients we used to give ganciclovir therapeutic dose for 5-7 days post-transplant then switch to valganciclovir therapeutic for 3weaks then prophylactic for 3-6m.
2. Medium risk patient (D+ to R+) who received depleting induction or desensitization we used to give them valganciclovir prophylactic dose for 3-6m post-transplant
3. Low risk patients (D+ to R+) with low immunological risk who didn’t receive depleting induction we follow frequent monitoring of CMV PCR and preemptive treatment.
CMV infection used to treat with ganciclovir in severe cases and valganciclovir in mild cases.
Therapeutic dose continued for at least 2 PCR -ve then switch to prophylactic dose beside decrease immunosuppression to accepted levels according to duration of transplant and severity of infection then switched to prophylactic dose for 6-9m by valganciclovir.
CMV resistance diagnosed by PCR quantitative titer which not responding or increasing although therapeutic optimum ganciclovir dose obtained according to eGFR for such cases we used to give CMV specific IVIG with stop MMF and CNI on the lower level.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation. CMV Prophylaxis:–
D-/R- No need for Val ganciclovir.
D+/R- using 200 days of Val ganciclovir.
D-/R+ and D+/R+ 100 days of Val ganciclovir and 200 days after ATG or Alemtuzumab.
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days.
5. The full prophylaxis dose is 900mg od and to be adjusted according to RFT. Surveillance and testing by indication in suspected CMV viraemia or disease.
1-CMV PCR on blood is the standard test for all transplant patients where CMV viremia or disease is suspected.
2-D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. Thresholds for treatment.
A. Patients that develop viremia or disease whilst not on prophylaxis
1.Treatment is mandatory in all cases of suspected tissue-invasive CMV disease.
2.Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with Val ganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with Val ganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis). Treatment:-
There are three options:
1. Oral Val ganciclovir 900mg BID for 21 days, then 900mg OD for 28 days or until 2 x PCR negative.
2. IV ganciclovir 5mg/kg BID for 5 days followed by oral Val ganciclovir 900mg OD until 2 x PCR negative.
3. IV ganciclovir 5mg/kg OD for 14-21 days, stop date determined by 2 x PCR negative. Reflect on your practice:
1-We are using Val ganciclovir as prophylaxis for 100 days and for those high risk or receiving ATG for 200 days.
2-We continue treatment till CMV viral load be undetectable for 2 weeks.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles 1. The serological status of the donor and recipient determines the risk of disease. 2. The intensity of immunosuppression determines the risk of disease. 3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease. 4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis. Prophylaxis
1. D+/R-: 200 days of valganciclovir. 2. D-/R+ and D+/R: 100 days of valganciclovir, 200 days after ATG or Alemtuzumab. 3. D-/R- No valganciclovir. 4. Prophylaxis should also be considered for any patient receiving intensified immunosuppressionat any time point beyond 100 days. 5. The full prophylaxis dose is 900 mg OD but note that dose reduction for renal impairment is commonly needed. Surveillance and testing by indication in suspected CMV viraemia or disease 1. Routine surveillance for viraemia is not required during prophylaxis. 2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days. 3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits as per the following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 weeks. 4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not. Thresholdsfortreatment A. Patients that develop viraemia or disease whilst not on prophylaxis:
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis:
· Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing. Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy.
Principles
1. Disease risk depends on donor and recipient serology.
2. Immunosuppression intensity determines illness risk.
3. Valganciclovir is authorised for prevention but widely used for therapy.
4. High-risk individuals (D+R-) remain at risk of CMV viraemia and infection despite prophylaxis. Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od Surveillance and testing by indication in suspected CMV viraemia or disease
1.During prophylaxis, viraemia surveillance is not required.
2. D+/R- individuals should have their CMV IgG serostatus tested around 200 days.
3. D+/R- patients should start CMV PCR surveillance after prophylaxis. If needed, extra “Bloods and Go” visits to RAU can do this:
2–4–8–12–weeks. The transplant team will coordinate.
4. CMV PCR on blood is the usual test for transplant patients with suspected CMV viraemia or disease, regardless of prophylaxis. Treatment thresholds
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. All suspected tissue-invasive CMV cases require treatment, regardless of viral load.
2. Lower immunosuppression in R+ patients with virus loads under 3 logs 10.
3. Treat symptomatic or quickly rising titre high-risk patients with valganciclovir if viral load reaches 3 logs 10.
4. Valganciclovir or IV ganciclovir is required for virus loads over 4 logs.
5. IV ganciclovir is recommended for enteric absorption issues (proven GI involvement, diarrhoea or vomiting).
6. Consultant decision: IV ganciclovir for serious organ involvement (e.g. pneumonitis, encephalopathy).
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss treatment options and resistance testing with a consulting virologist. Treatment
Thresholds and parameters decide oral versus IV therapy.
Three choices:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2x PCR negative, whichever comes first.
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days until 2 x PCR negative
Please reflect on your practice
In my practice we use valganciclovir for prophylaxis and treatment. Prophylaxis is either for 3 or 6 months based on recipients serology.
Principles
1. The serological status of the donor and recipient, and the intensity of immunosuppression determine the risk of disease.
2. Valganciclovir is licensed for prophylaxis and for the treatment of the disease.
3. After finishing the prophylaxis, high-risk patients (D+R-) continue to be at risk for CMV viremia and disease.
Prophylaxis1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed:
Surveillance and testing by indication in suspected CMV viraemia or disease1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- Patients should begin CMV PCR surveillance as soon as prophylaxis is complete. If necessary, additional “Bloods and Go” visits to RAU can be made in accordance with the following timetable to do, which may be more frequent than clinic appointments:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4. Whether on prophylaxis or not, CMV PCR on blood is the required test for all transplant patients when CMV viraemia or illness is suspected or a possibility in outpatients or inpatients.
Thresholds for treatmentA. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis
Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
TreatmentThe choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use)
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
======================================================
Please reflect on your practice
These are comprehensive and reliable guidelines. I can see obvious similarities with our center. ,
During the evaluation of transplantation, CMV serology is routinely done, and those with high clinical suspicion or patients with positive IgM should do PCR.
Patients with detectable viral loads will be given a treatment dose of valganciclovir arranged according to eGFR.
According to CMV determinations and immunosuppression inductions, recipients will be stratified into three groups: low, intermediate, and high risk. The intermediate- and high-risk groups were then given 900 mg OD for three months as prophylaxis.
Follow up clinically and with CBC for side effects.
PCR monitoring is offered every 2 weeks for this period.
This is a protocol of the prophylaxis,surveillance and treatment of CMV after renal transplantation 1.Prophylaxis:
For the higher risk status, D+/R- they give 200 days of valganciclovir
For moderate risk, D-/R+ and D+/R+: 100 days of valganciclovir unless the patient receive depleting agents where they give 200 mg
If both donor and recepient were negative they give no prophylaxis
The dose is 900 mg and should be adjusted according to renal function.
2. Surveillance:
if the patient is on prophylaxis no need for surveillance
If high risk serostatus should be checked after stopping prophylaxis and should start surveillance with PCR as needed probably every 2, 4,8 or 12 weeks.
If CMV viremia or CMV disease is suspected do blood PCR.
3. When to treat: A: PCR threshold for treatment
If the patient is still on prophylaxis and develop CMV invasive disease he should receive treatment irrespective of his viral load.
Just reduce IS doses in R+ recepient if the viral load is low below 3 logs 10
If more than 3 logs of 10 give treatment if having symptoms or rapidly rising titre
If the PCR is more than 4 logs of 10 you should give treatment
Give IV ganciclovir if there is concern about absorption as in D/V.
If disease is serious and severe ( pneumnitis or encephalitis) always give IV ganciclovir
B . Treatment:
Oral valganciclovir 900 mg bd for 3 weeks,then 900 mg od for 28 days or treat until PCR is negative in 2 consecutive samples.
The dose for IV ganciclovir is 5 mg/ kg for 5 days followed by valganciclovir 900 mg od for the rest of treatment as mentioned above.
You may need to give IV ganciclovir for the whole period of treatment ( 2 – 3 weeks)
Dose for ganciclovir and valganciclovir needs to be adjusted according to renal function
In the treatment of CMV you may need to consult a virology specialist if the case is not straightforward.
The protocol is for the surveillance, prophylaxis and treatment of CMV after renal transplantation
Risk factor for CMV infection include:
Donor and recipient serostatus: Highest risk is with D+/R- while the lowest risk is with D-/R-
Intensity of immunosuppression
Valganciclovir is the drug of choice for prophylaxis. However, it is also used for treatment
It is important to note that CMV infection can occur after completing the prophylaxis, more so for patients at high risk
Prophylaxis
Prophylaxis is with valganciclovir 900 mg once daily (dose adjusted for eGFR) and is between 100 days (D-/R+, D+/R+) or 200 days (D+/R-)
Prophylaxis is also recommended after treatment intensification after rejection episode
Surveillance
Routine surveillance is not recommended during prophylaxis
The serostatus should be checked for all D+/R- patients after completing prophylaxis and these recipients should have surveillance for CMV infection as they are a high risk group
Treatment
Treatment is mandatory for al histologically confirmed invasive disease
For CMV PCR less than 3 log 10, appropriate reduction of immunosuppression should be considered
For CMV PCR more than 3 log 10, or rapidly rising titres or symptoms of infection, treatment with an antiviral should be considered
For CMV PCR more than 4 log 10 ganciclovir or valganciclovir should be started
In cases of severe disease with organ involvement or inability to retain oral medications, IV ganciclovir should be started
The treatment doses of IV ganciclovir is 5 mg/kg and the dose for valganciclovir is 900 mg twice daily (have to dose adjust as per eGFR)
The treatment should be for a minimum of 2 weeks and after that stopped after getting 2 consecutive undetectable viral load
In Kenya, we do routine surveillance and pre-emptive treatment for CMV due to the high cost of valganciclovir. After treatment for ABMR or ACR, we do surveillance and pre-emptive treatment.
For patients who develop CMV disease, we treat with IV ganciclovir for 5 days then with valganciclovir if the patient is able to take orally
■ Sheffield Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
● prophylaxis of CMV after renal transplantation :
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
4. patient receiving intensified immunosuppression at any time point beyond 100 days
5. prophylaxis dose is 900mg od adjusted for renal function
● Surveillance in CMV viraemia or disease
1. Routine surveillance is not required during prophylaxis
2 . CMV IgG at 200 days in D+/R- patients
3 . CMV PCR at the end of prophylaxis in D+/R- patients
4. CMV PCR on blood is the standard test for all transplant patients
● Thresholds for treatment
☆ Viraemia or disease developing whilst not on prophylaxis
1. In case of suspected tissue-invasive CMV disease treatment is mandatory in all irrespective of viral load.
2. IR in R+ patients with a viral load < 1000
3. Valganciclovir when viral load > 1000 if symptomatic or high-risk patients.
4. Valganciclovir or IV ganciclovir is mandatory when viral load > 10000
5. IV ganciclovir in proven GI involvement
6. IV ganciclovir in severe organ involvement (pneumonitis, encephalitis)
☆ Viraemia or disease developing whilst on prophylaxis
1. A consultant virologist to agree best treatment regime and discuss resistance testing
● Treatment
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Dose adjustment for renal function
● In our practice we use valgancyclovir for prophylaxis for 3 – 6 months in these cases :
▪︎D+/R-
▪︎T cell depleting agents
☆ treatment with valgancyclovir for CMV disease or viremia except
when there is diarrhoea or vomiting or severe involvement (pneumonitis, encephalitis) then we use IV gancyclovir
Prophylaxis:
Determine serological status of D/R and intensity of IS:
– D+/R- 200 days of valganciclovir.
– D-/R+ & D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
– D-/R- No valganciclovir
– After receiving intensified IS at any time point.
-the dose should be adjusted for renal impairment is
Surveillance and testing;
– Routine surveillance is not required during prophylaxis
– D+/R- ; check CMV IgG & CMV PCR once they finish prophylaxis.
– CMV PCR checked in all suspected CMV viremia or disease.
Thresholds for treatment
A.CMV viraemia or disease whilst not on prophylaxis
– All cases of invasive CMV should be treated irrespective of viral load.
– Viral load < than 3 logs 10; reduce immunosuppression
– Viral load > 3 logs 10 or if symptomatic or rapidly rising titre ; treat with valganciclovir.
– Viral load > 4 logs 10 ; Treat with oral valganciclovir or IV ganciclovir.
-IV ganciclovir used if severe organ involvement or if enteric absorption reduced.
B. CMV viraemia or disease whilst on prophylaxis
– Cases should be discussed with a consultant virologist to agree treatment regime and discuss
resistance testing
Treatment
– Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,
whichever occurs first
– IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
– IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
In our center;
Majority of our patients D+/R- ( pediatric ), prophylaxis given for all 3-6 months.
For treatment; we treat similar to this protocol.
Please summarise this protocol The serological status of the donor and recipient determines the risk of disease The intensity of immunosuppression determines the risk of disease Valganciclovir is licensed for prophylaxis but can be used for the treatment of disease (D+R-) remain at risk of CMV viraemia and disease after prophylaxis.
Prophylaxis · D+/R- 200 days of valganciclovir. · D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab · D-/R- No valganciclovir · Prophylaxis for any patient receiving intensified immunosuppression at any time point beyond 100 days · The full prophylaxis dose is 900mg od adjust dose in renal impairment
Surveillance and testing by indication in suspected CMV viraemia or disease · Routine surveillance for viraemia is not rneeded during prophylaxis · D+/R- should have CMV IgG checked at or around 200 days · D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. · Extra “Bloods and Go” visits at – 2 weeks – 4 weeks – 8 weeks – 12 weeks · CMV PCR on blood is the standard test when CMV viraemia or disease is suspected
Threshold for treatment Patients that develop viraemia or disease whilst not on prophylaxis · Suspected tissue-invasive CMV disease · valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre · IV ganciclovir is indicated where enteric absorption is an issue · IV ganciclovir in systemic tissue involvement Development of viraemia or disease whilst on prophylaxis
Treatment Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice We give CMV prophylaxis to those having ATG for 3 months
I like your summary of these guidelines. I like that you have reflected of current practice in your hospital, but typing just one sentence is not good enough.
Serological status of the donor and recipient determines the risk of disease. Intensity of immunosuppression determines the risk of disease. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis:
D+/R- 200 days of valganciclovir 900mg OD depending renal function
D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
D-/R- No need prophylaxis
Surveillance and testing by indication in suspected CMV viraemia or disease.
Routine surveillance for viraemia is not required during prophylaxis
D+/R- should have their serostatus (CMV IgG) checked at or around 200 days
D+/R- should start surveillance with CMV PCR once finish prophylaxis
Thresholds for treatment
Patients that develop viraemia or disease whilst not on prophylaxis
Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs10.
IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis,encephalitis) – Consultant decision.
Treatment
There are three options:
Oral valganciclovir 900mg bd for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,whichever occurs first (off-label drug use).i
IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od* until 2 x PCRnegative.
IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
The dose need renal adjustment in reduced kidney function
*Principles:
1) The serological condition of both donor (D) and recipient (R) decide the risk of disease.
2) The strength of immunosuppression (IS) deciding the risk of disease.
3) Valganciclovir (vGCV) is permitted as prophylaxis; however, can be used for treatment.
4) High-risk patients (D+R-) still at risk of CMV viraemia and disease after they finish the prophylaxis.
*Prophylaxis
1) D+/R- 200 days of (vGCV).
2) D-/R+ and D+/R+ 100 days of (vGCV), 200 days after ATG or Alemtuzumab
3) D-/R- without (vGCV).
4) Consultation is recommended for any patient receiving heavy IS at any time point beside 100 days.
5) Complete prophylaxis dose is 900 mg OD; however, the dose should be reduced in case of renal impairment.
*Surveillance and testing by indication in suspected CMV viraemia or disease
1) Routine surveillance for viraemia is not need during prophylaxis
2) D+/R- patients should monitor (CMV IgG) at 200 days
3) D+/R- patients must start monitoring with CMV PCR after they complete the prophylaxis.
Extra “Bloods and Go” visits to RAU if required as per the following schedule: ( 2 weeks, 4 weeks, 8 weeks, 12 weeks).The recipient team will coordinate this.
4) Blood CMV PCR is the definitive test for CMV viraemia or disease in all suspected patients regardless on prophylaxis or not.
*Thresholds for treatment
A. Viraemia or disease in non prophylactic patients:
1) Treatment is necessary in all suspected cases of tissue-invasive CMV disease, in spite of viral load.
2) Recommended suitable reduction in IS in R+ patients with a viral load of less than 3 logs 10.
3) Advised treatment with (vGCV) when the viral load above 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4) Treatment with (vGCV) or IV ganciclovir (GCV) is necessary when the viral load above 4 logs 10.
5) IV (GCV) is advised where enteric absorption is likely to be compromised.
6) IV (GCV) is advised in severe organ involvement, and it is a consultant decision.
B. Viraemia or disease in prophylactic patients:
1. The consultant virologist should agree a better treatment regime and the resistance testing.
*Treatment:
*The option of oral or IV therapy is based on the above mentioned thresholds and criteria. *There are (3) options:
1) Oral (vGCV) 900mg BD for 21 days, then 900mg OD for 28 days or until 2 negative PCR tests.
2) IV (GCV) 5mg/kg BD for 5 days followed by oral (vGCV) 900mg OD until 2 x PCR negative.
3) IV (GCV) 5mg/kg BD for 14-21 days, stop date determined by 2 x PCR negative.
*** Dose reductions of both (vGCV & GCV) is recommended in renal impairment.
# Please reflect on your practice
Cytomegalovirus prophylaxis is recommended for:
(1)Patients who received ATG induction; (high to moderate risk)
(2)Patients who are CMV-IgG negative and received kidneys from CMV-IgG positive donor. The preferred agent is valganciclovir for 3 months.
1. Please summarise this protocol
1.The risk of disease is determined by the serological status of the donor & recipient.
2. The risk of disease is influenced by the degree of IS.
3. Although valganciclovir is licensed for prophylaxis, it is used for treatment as well.
4. After completing the prophylaxis, high-risk patients (D+R-) continue to be at risk for CMV viraemia & illness. Prophylaxis duration
1. D+/R- 200 days.
2. D-/R+ & D+/R+ 100 days, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Any patient on enhanced IS at any time point after 100 days should also be considered for prophylaxis, according to consultant decision.
5. The prophylaxis dose is 900mg od; dose reduction for renal impairment is needed: Renal Drug Handbook or pharmacist consultation. Surveillance and testing by indication in suspected CMV viraemia or disease
1. During prophylaxis, routine viraemia surveillance is not required.
2. At or close to 200 days, D+/R- patients should have CMV IgG tested.
3. D+/R-: start surveillance with CMV PCR once prophylaxis finished. This may be more frequent than clinic visits:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
4. CMV PCR on blood is the standard test where CMV viraemia or disease is suspected irrespective of whether on prophylaxis or not. Thresholds for treatment A. Patients who have viraemia or disease while not on prophylaxis
1. Treatment in all suspected tissue-invasive CMV disease, irrespective of viral load.
2. IS dose reduction in R+ patients with a viral load of fewer than 3 logs 10.
3. Valganciclovir treatment is necessary if a high-risk patient’s viral load > 3 log 10 & are symptomatic or a fast increasing viral titre.
4. When the viral load surpasses 4 logs 10, valganciclovir or IV ganciclovir treatment is required.
5. Where enteric absorption is compromised(proven (GI upset, diarrhoea or vomiting), IV ganciclovir is recommended.
6. Any patient with serious organ involvement (pneumonitis or encephalitis) should get IV ganciclovir, as determined by the consultant. B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss the optimal treatment plan, as well as resistance testing, with a virologist. Treatment
Options:
1. Oral valganciclovir 900mg bdx21 days, then 900mg od x 28 days or until 2 x PCR-neg.
2. IV ganciclovir 5mg/kg bdx5 days then oral valganciclovir 900mg od until 2 x PCR-neg.
3. IV ganciclovir 5mg/kg bdx14-21 days, stop date established by 2-neg PCR results.
N.B: dose reductions for renal impairment are needed with valganciclovir & ganciclovir ============================== 2. Please reflect on your practice
In our facility, valaganciclovir is given to high- to moderate-risk TX patients who are receiving ATG as induction therapy. Instead of the 200 days specified in these standards, we give it for 90 days only due to financial issues.
Summary
Prophylaxis is indicated according to the risk (serological status and intensity of IS)
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Based on consultant decision, Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days.
5. The full prophylaxis dose is 900mg od dose should be adjusted according to the creatinine clearance Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3 surveillance with CMV PCR once they finish prophylaxis should be started in D+/R- patients with more frequent than clinic visits and can be achieved with extra “Bloods and Go” at: – 2 weeks – 4 weeks – 8 weeks – 12 weeks The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not. Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. if the viral load of fewer than 3 logs 10, Consider appropriate reduction in immunosuppression in R+ patients with
3. If the viral load exceeds 3 logs 10 Consider treatment with valganciclovir when symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) or where in GIT involvement where absorption is likely to be affected
B. Patients that develop viraemia or disease whilst on prophylaxis case should be discussed individually consultant virologist to agree best treatment regime and discuss resistance testing Treatment
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation:
factors that determine of risk categorizations: 1.serological status of both D& R ( D+/ R- high risk , D+/R+ ,D-/R+ moderate risk, D-/R- low risk) 2.intensity of immunosuppressive medications at induction, maintenance & treatment of rejection episodes (alemtuzumab & ATG)
PROPHYLAXIS:
A. Medications such as valganciclovir and ganciclovir
B.Indications & durations: dosage 900 mg but require dose adjustment if renal impairment
1.high risk ……200 days
2.moderate risk …..100 days ,if after intensive immunosuppressive…..extended to 200 days
3.low risk …no need
note: high risk group remain risk of infection after prophylaxis has been finished
SURVEILLANCE:
A. during prophylaxis….. no need routinely but high risk ones require at the end of prophylaxis duration
B. after prophylaxis ……schedules at 2 weeks,4 weeks,8 weeks and 12 weeks
note: the standard investigation is CMV PCR on blood sample
Treatment :
A. when developing infection or disease while on prophylaxis:
required an MDT discussion with virologist and focus on work ups for identifying resistance strains
B. while not on prophylaxis
anti viral ……if viral load > 4 logs 10
antiviral ……symptomatic patient with viral load >3 logs 10
if suspected tissue-invasive CMV disease regardless of viral load
reduction of immunosuppressives in R+ with viral led < 3 logs 10
RX. ROUTE & DURATION:
either oral valganciclovir or IV ganciclovir
different duration protocols available ….generally for several weeks until 2 PCR will be negative
Protocol for prophylaxis, surveillance, and treatment of CMV after reanl transplantation- Sheffield Teaching Hospital.
Principles
The donor and recipient serological status determines the risk of disease, as well as the immunosuppression used.
Valgancyclovir is licensed for prophylaxis, but often used for treatment.
High risk donor +/ recipient – remains at risk of CMV viremia even after completion of prophylaxis.
Prophylaxis
D+/R- 200 days of Valgancyclovir.
D-/R+ AND D+/R+ 100 days of Valgancyclovir, and for 200 days for whom receiving ATG/Campath.
D-/R- NO prophylaxis needed.
Prophylaxis should be considered for any patient receiving intensive immunosuppression at any time beyond 100 days.
Prophylaxis dose is 900 mg once daily- renal dose adjustment is mandatory.
Surveillance and testing by indication in suspected CMV viraemia or disease
surveillance is not required during prophylaxis.
D+/R- patients should have their serostatus checked at or around 200 days.
CMV PCR is the standard test to diagnose CMV viremia or disease, irrespective whether on prophylaxis or not.
D+/R- patients should have CMV PCR once prophylaxis finished, and in the following schedule by the recipient team.
2 weeks.
4 weeks.
8 weeks.
12 weeks.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis:
Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis:
Consultant a virologist to agree best treatment regime and discuss resistance testing.
Treatment options
Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases. Additional therapy may be appropriate following the discussion.
Please reflect on your practice In our practice we use not to routinely monitor PCR, we use to order it when viremia or disease is suspected.
We use to give valgancylovir prophylaxis for 6 months for all high risk groups as forementioned, and for 3 months for the low risk groups.
The treatment protocol we use is 5 days if IV gancyclovir followed by oral valgancyclovir until x2 PCR negative.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation:
Aim of prophylaxis:
Serology status of donor and recipient
Intensity of immunosuppressive therapy
Valganciclovir is used for prophylaxis and treatment of disease
High risk patients with positive donor and recipient at risk of viremia and disease after complete prophylaxis.
Prophylaxis :
Patients with positive donor and negative recipient or both positive for prophylaxis 200 days.
Patients negative donor and positive recipient or both positive for 100 days valganciclovir.
Patients receive ATG or Alemtuzumab for prophylaxis 200 days.
Also prophylaxis for 100 days given to all patients receive intense immunosuppressive therapy.
Recommended dose is valganciclovir 900 mg and need dose adjustment in case of renal impairment.
Surveillance:
Monitoring of CMV by CMV igG test for 200 days in case of positive donor and negative recipient.
Positive donor and negative recipient should start serial monitoring of CMV PCR every 2wk/ 4wk/ 8wk and 12wk.
CMV PCR is the test for diagnosis of all transplanted patients with CMV viremia and disease.
Thresholds for treatment:
Treatment is mandatory of all patients with CMV viremia and disease irrespective to viral load.
Reduction of immunosuppressive therapy with viral load less than 3 log 10.
Treatment with valganciclovir if patient symptomatic and viral load 3or more log 10.
Intravenous ganciclovir if viral load 4 log 10.
Intravenous ganciclovir in patients with systemic CMV infection ( colitis, pneumonitis and encephalitis.
If patient develop viremia while in prophylaxis should refer and discuss with infectious consultant.
Treatment:
Oral valganciclovir 900mg twice a day for 21 days, then 900mg once a-day for 28 days or until 2 x PCR negative.
2. IV ganciclovir 5mg/kg twice a day for 5 days followed by oral valganciclovir 900mg once a day until 2 x PCR negative.
3. IV ganciclovir 5mg/kg twice a day for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice
We use prophylaxis of ganciclovir same as this protocol
I like your summary of these guidelines. I like that you have reflected of current practice in your hospital, but typing just one sentence is not good enough.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles
1. The risk of illness depends on the serological status of the donor and recipient.
2. The risk of disease is influenced by the degree of immunosuppression.
3. Although valganciclovir has a license for prophylaxis, it is frequently utilized for illness treatment as well.
4. After finishing the prophylaxis, high-risk patients (D+R-) continue to be at risk of CMV viraemia and illness. Prophylaxis;
1. 200 days of valganciclovir therapy.
2. 100 days after valganciclovir, 200 days after ATG, and D-/R+ and D+/R+
3. No valganciclovir in D-/R-
4. Any patient getting enhanced immunosuppression at any time point after 100 days should also be given consideration for prophylaxis, according to consultant opinion.
5. The complete prophylactic dose is 900 mg od, however it should be noted that dose reduction for renal impairment is frequently required; for the proper regimen and to be revised in the case of altered renal function, consult the Renal Drug Handbook or your pharmacist.
Surveillance and testing by indication in suspected of CMV virimia or disaease
1. During prophylaxis, routine viraemia surveillance is not necessary.
2. At or close to 200 days, D+/R- patients should have their serostatus (CMV IgG) tested.
3. After completing prophylaxis, D+/R- patients should begin surveillance with CMV PCR. If necessary, additional “Bloods and Go” visits to RAU might be made in accordance with the following timetable to do this, which might be more frequently than clinic visits.
– 2 weeks, 4 weeks, 8 weeks and 12 weeks
4. Whether or whether prophylaxis is being taken, CMV PCR on blood is the routine test for all transplant patients when CMV viraemia or illness is suspected or a possibility in outpatients or inpatients.
Threshold of treatment
Patients that develop viraemia or disease whilst not on prophylaxis
1. Regardless of viral load, treatment is required in all suspected tissue-invasive CMV illness cases.
2. For R+ patients with a viral load of under 3 logs 10, suitable immunosuppressive decrease should be considered.
3. When the viral load in high-risk patients exceeds 3 logs 10 and they are symptomatic or their viral titre is rising quickly, consider starting valganciclovir treatment.
4. When the viral load exceeds 4 logs 10, valganciclovir or IV ganciclovir treatment is required.
5. Where enteric absorption is likely to be limited (proven GI problems, diarrhoea or vomiting), IV ganciclovir is suggested.
6. Any patient with serious organ involvement (such as pneumonitis or encephalopathy) requires IV ganciclovir, as determined by the consultant. Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,
whichever occurs first (off-label drug use). I
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please be aware that dose reductions for renal impairment are frequently required while using valganciclovir and ganciclovir therapy; for an appropriate regimen, check the Renal Drug Handbook or your pharmacist, and make any necessary revisions if your kidney function changes.
In less straightforward circumstances, it is advisable to seek the counsel of specialists in virology, pharmacy, and other fields.
After the discussion, additional counseling may be necessary.
Our practice reflect the same as guilines.
I like your summary of these guidelines. I like your reflection of current practice in your hospital. ‘Guidelines’ got mistyped as ‘guilines’ in last line. .
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles
The donor and recipient serological status and intensity of immunosuppression determines the disease risk.
Valganciclovir is licensed for prophylaxis and treatment.
High-risk patients (D+R-) remain at risk after completing prophylaxis. Prophylaxis
D+/R- 200 days of valganciclovir.
D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab.
D-/R- No prophylaxis.
Consider prophylaxis after a period of intense immunosuppression.
The dose is 900mg od, adjusted according to renal function. Surveillance and testing by indication in suspected CMV viraemia or disease
No surveillance during prophylaxis.
Check serostatus around 200 days in D+/R- patients and start surveillance at 2, 4, 8 and 12 weeks after completing prophylaxis.
Blood CMV PCR is the standard test where viraemia is suspected. Thresholds for treatment Patients not on prophylaxis
Treat all suspected tissue-invasive disease, irrespective of viral load.
Consider IS reduction in R+ patients with a viral load of < 3 logs.
Consider treatment when viral load> log 4 or > log 3 if symptomatic or rapidly rising titre in high-risk patients.
Consider IV ganciclovir in severe organ involvement or when enteric absorption is compromised. Patients on prophylaxis
Discuss all cases with a virologist, consider resistance testing Treatment
There are three options:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative.
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 day until 2 x PCR negative.
Our centre is more or less the same except that after the prophylaxis period, we monitor CMV monthly for the first year after transplant.
Please summarise this protocol Principles
-The serological status and intensity of immunosuppression determine the risk of disease.
-Valganciclovir is lused for prophylaxis and treatment of disease.
-D+/R- remain at risk of CMV viraemia and disease after they complete the prophylaxis. Prophylaxis
-D+/R- 200 days of valganciclovir.
– D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
– D-/R- No valganciclovir
-The full prophylaxis dose is 900mg od but adjust the dose according to renal impairment. Surveillance and testing by indication in suspected CMV viraemia or disease
-Routine surveillance for viraemia is not required during prophylaxis.
-D+/R- patients should have their serostatus checked at or around 200 days.
-D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
– CMV PCR on blood is the standard test for all transplant patients. Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
-Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
-Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
-Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
-Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
-IV ganciclovir is indicated where enteric absorption is likely to be compromised . B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing Treatment
-The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.
There are three options:
– Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative .
– IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
-IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative. Please reflect on your practice
-In our center, we screen the donor and recipient pre-transplant.
-We transplant D+/R+ or D-/R+, so we give valganciclovir prophylaxis dose for 100 days.
-In treatment, we use either valganciclovir or ganciclovir therapy.
Summary of the protocol of prophylaxis, surveillance, and treatment of CMV after renal transplantation: Principle:
The serological status of the donor and recipient determines the risk of disease.
The intensity of IS determined the risk of disease.
Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
High-risk patients(D+R-) remain at risk of CMV viremia and disease after they complete the prophylaxis.
Prophylaxis:
D+/R- == 200 days of valganciclovir.
D-/R+ == 100 days of valganciclovir, 200 days after ATG or alemtuzumab.
D-/R- == no valganciclovir
Prophylaxis should also be considered for any patient receiving intensified IS at any time point beyond 100 days – Consultant decision.
The full prophylaxis dose is 900 mg OD but note that dose reduction fpr renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viremia or disease
Routine surveillance for viremia is not required during prophylaxis.
D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
D+/R- should start surveillance with CMV PCR once they finish prophylaxis, and this can be more frequent than clinic visit as per the following schedule:
2 weeks.
4 weeks.
8 weeks.
12 weeks.
The recipient team will coordinate this. 4.CMV PCR in the blood is the standard test for all transplant patient where CMV viremia or disease is suspected or a possibility in outpatient and inpatient, irrespective of whether on prophylaxis or not.
Threshold for treatment: A. patient that develops viremia or disease whilst not on prophylaxis;
Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
Consider appropriate reduction in IS in R+ patients with a viral load of fewer than 3 logs 10.
Consider treatment with valganciclovir when the viral load exceeds 3 log 10 if symptoms or rapidly rising titr in high-risk patients.
Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 log 10.
IV ganciclovir is indicated where enteric absorption is likely to be compromised.
IV ganciclovir is indicated in any patient with sever organ involvement-Consultant decision.
B. patients that develop viremia or disease whilst on prophylaxis:
Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment: The choice of oral vs IV therapy is determined by the above-mentioned threshold and criteria; there are three options:
Oral valganciclovir 900 mg BD for 21 days, then 900 mg OD for 28 days or until 2 * PCR negative, whichever occurs first.
IV ganciclovir 5 mg/kg BD for 5 days followed by oral valganciclovir 900 mg OD until 2*PCR negative.
IV ganciclovir 5mg/kg BD for 14-21 days, stop date determined by 2*PCR negative.
I like your summary of these guidelines. I like that you have reflected of current practice in your hospital, but typing just 4 words in this heading is not good enough.
Please summarise this protocol
This is Sheffield teaching hospitals protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation, July 2016 (3rd revision), reviewed July 2019
*The risk of diseases is determined by:
1. Serostatus of the donor and recipient
2. Intensity of immunosuppression
*Valganciclovir is for prophylaxis and treatment
*The risk is still there after complete prophylaxis in high risk patients (D+R-)
Prophylaxis (indications and duration)
Valganciclovir with a dose of 900mg (with dose reduction for renal impairment)
Indications include:
1. D+/R- (200 days)
2. D-/R+ and D+/R+ (100 days of valganciclovir, 200 days after ATG or Alemtuzumab)
3. Intensive immunosuppression at any time point beyond 100 days (Consultant decision)
No prophylaxis in D-/R-
Surveillance (CMV IgG and CMV PCR)
Routine surveillance is not required during prophylaxis
D+/R- : check serostatus (CMV IgG) at or around 200 days
D+/R- : once they finish prophylaxis, with CMV PCR (2 weeks – 4 weeks – 8 weeks – 12 weeks)
CMV PCR on blood is the standard test where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not
Treatment threshold
viraemia or disease whilst not on prophylaxis
*Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load
*Reduce immunosuppression in R+ with a viral load of < than 3 logs 10
* Valganciclovir when the viral load > 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients
*Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10
*IV ganciclovir is indicated when enteric absorption problem (proven GI involvement, diarrhoea or vomiting)
*IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision
viraemia or disease whilst on prophylaxis
*Discuss all such cases with a consultant virologist
Treatment Options include (oral versus IV therapy is determined by the abovementioned thresholds and criteria):
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative
3. IV ganciclovir 5mg/kg bd for 14-21 days (stop date determined by 2 x PCR negative)
Please reflect on your practice
We do not give prophylaxis (most patients are D+/R+). Management depends on clinical suspicion, viral load, and histopathology. We give valganciclovir for treatment (no viral load monitoring). No post transplant survey and pre-emptive treatment
I like your summary of these guidelines. I like your reflection of current practice in your hospital. Perhaps you wanted to type ‘No post transplant surveillance’ rather than ‘No post transplant survey’.
1- D-/R- …….. No prophylaxis with valganciclovir is needed.
2- D+/R- …….. prophylaxis is needed with Valganciclovir for 200 days to # 1ry infection.
3- R+ with any donor ….. prophylaxis is needed with Valganciclovir for 100 days, 200 days after ATG or Alemtuzumab
NB1. Prophylaxis should also be considered for any patient receiving intensive immunosuppression at any time after 100 days NB2. The usual prophylaxis dose is 900 mg od with dose reduction in CKD.
Surveillance :
1- D+/R- …..
a- Check CMV IgG at 6 months. b- Check CMV PCR at the end of prophylaxis and then after 2,4,8,12 weeks
Treatment :
1- Oral valganciclovir 900mg twice daily for 3 weeks, then 900mg once daily for 4 weeks or until 2 consecutive negative PCR tests whichever is shorter.
2- IV ganciclovir 5mg/kg twice daily for 5 days followed by oral valganciclovir 900mg once daily until 2 consecutive negative PCR tests.
3- IV ganciclovir 5mg/kg twice daily for 2-3 weeks and stop ttt if 2 consecutive negative PCR tests.
Please reflect on your practice :
for prophylaxis and surveillance, it is the same as in common practice.
for treatment, oral ttt is the standard as it is widely available.
CMV infection is commonly encountered in the context of renal transplantation with detrimental consequences and heightened mortality and morbidity. The guideline advocates prophylactic protocol depending on risk factor determined by virology status and intensity of immunosuppression therapy.
Therefore, in status of D+/R- which is the riskiest setting for attracting CMV infection, valgranciclovir is implemented prophylactically for 200 days. Nevertheless, risk of infection is still significant post prophylactic, and having CMV PCR status checked is indicated post prophylaxis on regular basis, after having CMV IgG status scrutinized towards end of prophylaxis period.
Valganciclovir 900 mg per day is drug of choice for prophylaxis and treatment.
in other status of sero-positivity D-/R+ and D+/R+ a prophylaxis course of 100 days is warranted, except when lymphocytes depleting agent ATG or Alemtuzumab was used, then similar course of 200 days prophylaxis is indicated.
in D-/R- sero-status, no prophylaxis protocol is indicated . Treatment is indicated for all invasive CMV infection regardless to viral load.
reduction of immunosuppression is indicated when viral load is less than 3 log 10.
More than 3 log 10 or rising titer Valganciclovir is considered.
More than 4 log 10 Valganciclovir is mandatory.
Principles
1. Donor and recipient serology determine illness risk.
2. Immunosuppression intensity determines illness risk.
3. Valganciclovir is authorized for prevention but widely used for therapy.
4. High-risk individuals (D+R-) remain at risk of CMV viremia and illness despite prophylaxis.
Prophylaxis
D+/R- 200 days valganciclovir.
2. D-/R+ and D+/R+ 100 days valganciclovir, 200 days following ATG or Alemtuzumab
3. D- /R- Valganciclovir-free
4. Consultants should consider prophylaxis for patients receiving increased immunosuppression beyond 100 days.
5. The complete prophylaxis dosage is 900mg OD; however, renal impairment sometimes requires dose reduction.
Suspected CMV viremia or illness surveillance and testing.
1. Prophylaxis does not need viremia monitoring.
2. D+/R- patients should be tested for CMV IgG at 200 days.
3. D+/R- patients should start CMV PCR monitoring after prophylaxis. If needed, more “Bloods and Go” trips to RAU may do this:
2–4–8–12–weeks
The receiving team will coordinate.
4. All transplant patients with suspected CMV viremia or illness have a blood CMV PCR.
Treatment thresholds
non-prophylactic patients with viremia or illness.
1. All suspected tissue-invasive CMV cases need treatment, regardless of viral load.
2. Lower immunosuppression in R+ patients with virus loads under 3 logs. 10.
3. Treat viral loads above 3 logs with valganciclovir. 10 if high-risk or symptomatic.
4. Valganciclovir or IV ganciclovir is required when the viral load reaches 4 logs.
10.
5. In cases of GI involvement, diarrhea, or vomiting, IV ganciclovir is recommended.
6. Consultant decision: IV ganciclovir for serious organ involvement (e.g., pneumonitis, encephalopathy).
Prophylaxis patients with viremia or illness
1. Discuss all cases with a specialist virologist to determine the optimal therapy and resistance testing.
Treatment Based on the above thresholds and criteria, the choice between oral and IV therapy is made.
There are three options:
1. Valganciclovir 900 mg bd* for 21 days, then 900 mg od* for 28 days, or until two PCR tests are negative, whichever comes first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice
We are consulting the ID team for any case of CMV disease, and they are nearly following the same lines of treatment.
Regarding the prophylaxis: all our patients receive prophylaxis for 3 months except D+ to R-VE and the patient who received ATG. We are extending the prophylaxis to 6 months.
Principles; —————————-
1-The serological status of the donor and recipient determines the risk of disease.
2-The intensity of immunosuppression determines the risk of disease.
3-Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4-High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis; —————————————
1-low risk group (D-/R-)
no need to give valganciclovir .
2-Intermediate risk group (D-/R+ and D+/R+)
100 days of valganciclovir .
3-High risk group (200 days Valganciclovir)
a- D+/R- .
b- Intermediate risk groups ,if they received T-cell depleting agent .
4-Those,who received intensified immunosuppressant ; Prophylaxis should be considered .
5-The standard adult prophylactic dose is 900 mg od and the dose should be adjusted according to the creatinine clearance in case of renal impairment .
Surveillance and testing by indication in suspected CMV viraemia or disease; ———————————————————————————————————
1-Survveillance for viraemia is recommended in the following groups o patients ;
a- D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
b- D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if
required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment; ——————————————————————————————-
A-Patients that develop viraemia or disease whilst not on prophylaxis;
1-Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2-According to the viral load consider the following ;
A-reduction o immunosuppression ,if the viral load is of less than 3 logs 10.
B-Valganciclvir ,if ;
The viral load exceeds 3 logs 10 .
symptomatic .
rapidly rising titre in high-risk patients.
C-Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
3. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
4. IV ganciclovir is indicated in any;
A- patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis.
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment; ——————————————–
The choice of oral versus IV therapy is determined by the above mentioned thresholds and criteria.
There are three options:
1-Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2-IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3-IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy .
Please reflect on your practice; ———————————————————– We do not routinely screened recipient unless there a clinical suspicion. Oral valganciclovir is recommended for prophylaxis in high risk patient and mild disease . Intravenous ganciclovir is recommended for severe invasive disease .
I like your summary of these guidelines. Typing the whole sentences as the last paragraph amounts to shouting. I like your reflection of current practice in your hospital.
I like that your reflection of current practice in your hospital and a mention of limitations that include no ganciclovir being available in Nigeria. I wish you could type references to support your arguments.
1- Serological status of the donor and recipient and the degree of immunosuppression are important risk factors of CMV disease.
2- D+/R- still at high risk even if complete their CMV prophylaxis treatment
3- Valganciclovir used as a prophylactic treatment by a dose 900 mg OD and can be adjusted according to renal function and used for 200 days in D+/R- and for 100 days in D-/R+ or D+/R+ and used for 200 days if received ATG or Alemtuzumab, but should not be given in D-/R-.
4- CMV IgG should be checked in D+/R- at 200 days, and PCR should be done after finishing prophylaxis then scheduled at two, 4,8,12 weeks.
5- Treatment should be started: in all cases of suspected tissue invasive CMV disease regardless the viral load by IV ganciclovir, and also in the cases of viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
6- Consider wise reduction of immunosuppressive medications
7- Treatment options: provided renal dose adjustment
a- Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first.
b- IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
c-IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
in my practice we used valganciclovir (valcyte) in prophylaxis in high risk patient D+/R- or D+/R+ or when using ATG as induction or in the treatment of ACR for 3-6 months.
and we used iv ganciclovir in treating suspected tissue invasive CMV disease
of course renal dose adjustment is needed and requested
Risk of CMV infection increased according to serological status recipient & donor & intensity of immunosuppression
Valganciclovir(VGC) can be used as CMV prophylaxis and treatment.
Valganciclovir as prophylaxis protocol include 200 days of VGC for D+/R-, 100 days of VGC for D-/R+ & D+/R+ & extended to 200 days if T cell depleted agent used as induction, & no need for prophylaxis for D-/R-.
In D+/R- patients CMV PCR should be checked after prophylaxis discontinuation.
All suspected CMV patient should send for CMV PCR>
Threshold for CMV treatment:
CMV disease developed while the patient not on prophylaxis
suspected invasive CMV infection should be treated regardless CMV viral load.
viral load >3log10 with symptoms or rapidly rising viral load in high risk patient should be treated with VGC.
viral load >4logs10 patients should be treated with oral VGC (Iv used if intestinal absorption compromised ) or IV ganciclovir ( also used in sever organ involvement).
Viremia development while patient on prophylaxis should be treated after discussion with consultant virologist about the best treatment regime and resistant test.
Treatment:
oral VGC 900mg bd for 21 days, 900mg od for 28 days or until 2 consecutive PCR result negative.
IV ganciclovir 5mg/kg bd for 5 days then oral VGC 900mg od until 2 PCR result are negative.
IV ganciclovir 5mg/kg for 2-3 weeks & treatment discontinuation depend on PCR result.
In my practice VGC used as prophylaxis for 3-6 months in D+/R+ & D+/R-.
Treatment of CMV disease with VGC 900mg bd then od until negative result of CMV PCR.
In Brazil, we do not have oral Valganciclovir, but we do have oral Ganciclovir.
D+/R-
Oral ganciclovir for six months starting fifteen days after transplantation
D+/R+
rATG 3mg/kg + CNI + mTor – monitor symptoms only
rATG 3mg/kg + CNI + MMF – oral ganciclovir for three months starting fifteen days after the transplant
rATG 6mg/kg + CNI + MMF – oral ganciclovir for six months starting fifteen days after the transplant
HIV positive – oral ganciclovir for three months starting fifteen days after transplantation
D-/R-
Just monitor symptoms. CMV PCR assay every two weeks for three to six months.
If PCR is greater than 2000, initiate intravenous Ganciclovir for at least 14 days and only suspend treatment when PCR is negative.
Dose for oral Ganciclovir prophylaxis – 250mg / 1000mg tablet three times a day
Correct the dose for renal function.
I like that your reflection of current practice in your hospital and a mention of limitations that include no oral ganciclovir being available in Brazil.
I wish you could type references to support your arguments.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation. 1-Please summarise this protocol;
-The serological status of the donor and recipient determines the risk of disease.
-The intensity of immunosuppression determines the risk of disease. Prophylaxis;
-D+/R- 200 days of valganciclovir.
-D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab.
-D-/R- No valganciclovir.
-The full prophylaxis dose is 900mg od.
-The dose reduction for renal impairment is commonly needed (adjusted the dose according eGFR). Thresholds for treatment;
-Routine surveillance for viraemia is not required during prophylaxis
-CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not. Patients that develop viraemia or disease whilst not on prophylaxis;
-Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
-Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
-Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients. Patients that develop viraemia or disease whilst on prophylaxis;
Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing. Treatment;
-Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
-IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
-IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis)
1-Oral valganciclovir 900mg bd (for 21 days), then 900mg od (for 28 days) or until 2 x PCR negative, whichever occurs first.
2-IV ganciclovir 5mg/kg bd (for 5 days) followed by oral valganciclovir 900mg od until 2 x PCR negative.
3-IV ganciclovir 5mg/kg bd (for 14-21 days, stop date determined by 2 x PCR negative. 2-Please reflect on your practice; -In our practice, almost the same protocol is applied; -Prophylaxis offered for D+/R+ & D+/R- with valganciclovir for 3-6 months according
The serological status of the donor and recipient & The intensity of immunosuppression (including Induction & Maintenance therapy.
-Treatment (with advice of ID guided by Clinical pharmacist) ,we follow nearly the same protocol;
(Oral valganciclovir 900mg bd for 21 for 3/weeks, then 900mg od for 4/weeks or until 2 x PCR negative), or (IV ganciclovir 5mg/kg bd for 2/weeks , stop date determined by 2 x PCR negative).
CMV D+/R- transplant recipient should receive prophylactic therapy in the form of valgancyclovir 900 mg once daily for 200 days after transplantation
CMV R+ transplant recipient should receive prophylactic therapy in the form of valgancyclovir 900 mg once daily for 100 days after transplantation
CMV D-/R- transplant recipient should not receive prophylactic therapy for CMV
Any patient receive intensive immunosuppression after the first 100 days should receive valgancyclovir prophylaxis for 28 days
Surveillance
Surveillance is not indicated during prophylaxis
Surveillance is not indicated in non-high risk patients (those with R+ and D-/R-)
After prophylaxis surveillance is only indicated in high risk patients (D+/R-), PCR should be done at 200 days after transplantation (after finishing prophylaxis), then after 2, 4, 8 and 12 weeks after stopping prophylaxis
Indications of treatment with antiviral agent
Tissue invasive CMV disease
PCR > 1000 copies/ml if the patient is symptomatic or asymptomatic patients with either high risk (D+/R-) or non-high risk (R+) with rising titer during follow up.
PCR > 10000 copies/ml whatever the serostatus of the recipient
Otherwise reduction of immunosuppression alone is enough
Medications used for treatment of CMV infection
1- Oral valgancyclovir
In a dose of 900 mg twice daily
Indicated in asymptomatic cases and in mild to moderately symptomatic cases, provided the patient can take oral
The drug has renal dose adjustment
2- IV gancyclovir
In a dose of 5mg/kg/12 hours
In symptomatic severe and life-threatening cases and in patients with compromised GIT absorption
The drug has renal dose adjustment
Protocol
Follow up CBC, renal function test and CMV PCR weekly during treatment
The treatment should be given for a minimum of 2-3 weeks (2 weeks for IV and 3 weeks for oral), after 2 successive negative PCR readings 1 week apart, and the patient should be symptom free
Iv gancyclovir if given can be given for the total duration or till the condition stabilize (for 5 days) and the patient can take oral at that times switch to oral valgancyclovir can be done.
After treatment of CMV, prophylaxis should be initiated using valgancyclovir in a dose of 900 mg daily for 28 days
In my practice
We use valacyclover (Valtrex 500 mg) in prophylaxis once daily for 3-6 months according to the serostatus as it is cheaper and we reserve valgancyclovir for treatment
We use IV gancyclovir for severe tissue invasive disease till the condition stabilized then we switch to oral treatment till the patient is asymptomatic and PCR negative for 2 successive samples
In non-severe cases we give oral valgancyclover (valcyte ) for the whole course
Donor and recipients serostatus determine risk of disease.
Intensity of immunosuppression determine the risk of disease.
High risk (D+/R-) remain high risk of viremia and disease even after prophylaxis.
Prophylaxis protocols
D+/R- valganciclovir for 200 days
D+/R+ OR D-/R+ valganciclovir 100 days
D-/R- no need for prophylaxis
CMV viremia
No need for routine surveillance during prophylaxis
D+/R- should have CMV IgG and CMV PCR done on blood after prophylaxis then 2,4,8,12 weeks
Treatment
Treat any suspected case of tissue invasive disease regardless of viral load.
Reduce immunosuppression in recipient+ with fewer than 3 log viral load.
Start valganciclovir in symptomatic recipient with more than 3 log viral load or rapidly rising titers.
IV ganciclovir indicated when there is tissue invasive disease or oral absorption is compromised.
PO valganciclovir 900mg bd for 21 days then 900mg od for 28days or until 2 PCR are negative.
IV ganciclovir 5mg/kg bd for 5 days then PO valganciclovir 900mg od until 2 PCR negative.
IV ganciclovir 5mg/kg bd for 14-21 days.
Ganciclovir and valganciclovir should be renal dosed.
My practise
We are in a resource limited setting so we don’t routinely do prophylaxis.
Also there are fewer cases of D+/R-.
We treat preemptively based on the symptoms and viral load.
We usually give valganciclovir 900mg bd for 21 days then 900mg od for 28days.
Routine monitoring of viremia not done.
Histology for tissue invasive disease also not routinely done due to financial constraints.
I like your summary of these guidelines. I like that your reflection of current practice in your hospital. I must make comment on histology. Often histology is not really needed.
Risk of CMV infection increased according serological status of both donor & recipients & intensity of immunosuppression.
Valganciclovir can be used as CMV prophylaxis & treatment
Valganciclovir as prophylaxis: for 200 days in D+/R-, 100 days for D-/R+ & D+/R+ & for 200 days if T cell depleted agent used, and D-/R- no need for prophylaxis.
In D+/R- patients CMV PCR checked after prophylaxis discontinuation.
All suspected CMV patients should send for CMV PCR.
Threshold for treatment:
CMV disease developed while patient on no prophylaxis:
Suspected invasive CMV infection should be treated regardless viral load.
Viral load <3logs10, immunosuppression should be reduced.
viral load >3logs10 with symptoms or rapidly Rosing viral load in high risk patients should be treated with valganciclovir.
Viral load >4logs10 should be treated with oral valganciclovir (IV used if enteric absorption is compromised) or IV ganciclovir ( also used in sever organ involvement).
Viremia development while patient on prophylaxis: Patient treatment should be decided after discussion with consultant virologist about the best treatment regime & resistant test.
Treatment:
Oral valganciclovir 900mg bd for 21 days, the 900mg od for 28 days or until 2 PCR result are undetected.
IV ganciclovir 5mg/kg bd for 5 days, then oral valganciclovir 900mg od until 2 PCR result became undetected.
IV ganciclovir 5mg/kg bd for 2-3 weeks & treatment discontinuation depend on result of PCR.
In my practice CMV prophylaxis offered for D+/R+ & D+/R- with valganciclovir for 3-6 months. Treatment of CMV disease with valganciclovir 900mg bd then 900mg od until CMV PCR is undetected.
D+/R- is high risk patient; 200 days prophylaxis is needed
D-/R + and D+/R +: 100 days of valcyclovir after T-cell depletion therapy
The dose of valgancylovir is adjusted according to renal function
Surveillance and testing:
D+/R- : check CMV Ig G at 200 days, start surveillance (CMV PCR) after treatment at 2 weeks, 4 weeks, 8 weeks, & 12 weeks
Threshold for treatment:
A.CMV viraemia or disease in absence of prophylaxis:
Treat all patients with invasive disease regardless of their viral load
Decrease immune-suppression if CMV viral load < 3 logs 10
Treat all patients with viral load > 4 logs 10
Consider IV valganciclovir in cases of gastrointestinal disease as patients may have absorption problems ( e.g., diarrhea, vomiting ) with oral drugs .
B.CMV viraemia or disease in the presence of prophylaxis:
Consult with virologist
You may require viral genotype testing
Treatment: Drug doses are modified according to the renal function
Oral valgancyclovir 900 bd for 21 days, then 900 mg od for 28 days or until you get 2 consecutive negative PCR
IV ganciclovir 5 mg/kg bd for 5 days followed by oral valgancyclovir 900 mb bd until 2 consecutive negative PCR
IV ganciclovir 5 mg/kg bd for two to three weeks until you get 2 consecutive negative PCR
My practice:
Low resource setting; the drugs , PCR testing are extremely expensive
We don’t apply prophylaxis due to cost implications and high risk group (D+/ R-) are rare in our set up
We go for directly for treatment based of the clinical symptoms and PCR +/- histology
Our treatment protocol is something like this; Oral valgancyclovir 900 bd for 21 days, then 900 mg od for 28 days; monitoring may be an issue
Main ideas
-Detecting the virological status of the donor and the recipient is mandatory to assess the CMV infection risk
-Immunosuppression burden affects the risk
-Valganciclovir can be used for prophylaxis and treatment
-D+R- high risk patients are liable to develop CMV viraemia and disease after finishing the prophylactic course. Prophylaxis
200 days of valganciclovir for D+/R- .
100 days of valganciclovir and 200 days after ATG or Alemtuzumab for D-/R+ and D+/R+
Valganciclovir is not indicated for D-/R-
Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time after 100 days
Dose adjustment is needed for cases with renal impairment Suspected CMV viraemia or disease must be screened
During prophylaxis ,viremia surveillance is not a must
CMV IgG need to be checked at 200 days for D+/R- cases as well as checking CMV PCR once prophylaxis has ended as the latter test in blood is the standard test. Treatment threshold Cases that have viremia or disease without being on prophylaxis
· All cases with suspected tissue-invasive CMV disease must receive treatment regardless of viral load
· For R+ cases with a viral load less than 3 logs 10 ,immunosuppression need to be decreased
· If viral load is more than 3 logs 10 in symptomatic or rapidly rising titre in high-risk patients ,valganciclovir will be needed
· Valganciclovir or IV ganciclovir is crucial if viral load is more than 4 logs10.
· If enteric absorption is impaired, or severe organ involvement is detected , IV ganciclovir will be indicated Cases that have viremia or disease whilst on prophylaxis
Those caseshave to be comanaged with consultant virology Treatment
Oral versus IV therapy is chosen according to the same criteria as prophylaxis.
3 choices
-Oral valganciclovir 900mg bid for 21 days, then od for 28 days or till PCR negative twice
-IV ganciclovir 5mg/kg bd for 5 days then oral valganciclovir 900mg od until PCR
negative twice .
-IV ganciclovir 5mg/kg bd for 14-21 days, ends when PCR is negative twice
Both valganciclovir and ganciclovir need renal dose adjustment in cases with renal impairment
For screening During prophylaxis ,viremia surveillance is not a must CMV IgG need to be checked at 200 days for D+/R- cases as well as checking CMV PCR once prophylaxis has ended as the latter test in blood is the standard test. For prophylaxis in D+/R- 200 days of valganciclovir . in D-/R+ and D+/R+ 100 days of valganciclovir and 200 days after ATG or Alemtuzumab in D-/R- Valganciclovir is not indicated for treatment (3 options) -Oral valganciclovir 900mg bid for 21 days, then od for 28 days or till PCR negative twice -IV ganciclovir 5mg/kg bd for 5 days then oral valganciclovir 900mg od until PCR negative twice . -IV ganciclovir 5mg/kg bd for 14-21 days, ends when PCR is negative twice
Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but consider modification of dose according to renal function.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Reduce immunosuppression in R+ patients with a viral load of < 3000
3. Consider treatment with valganciclovir when the viral load> 3000 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised.
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options: 1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Consider dose reductions for renal impairment.
Our practice:
Our population is almost all D+/R+ hence we are giving prophylaxis with valganciclovir for all, for 3m.
we do modify the dose according to renal function.
For treatment, we give valganciclovir for 2-3 weeks and monitor PCR till 2 results are negative, then stop.
III.Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation.==================================================================== Please summarise this protocol
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles
Valganciclovir is licensed for prophylaxis but is often also used for the treatment of CMV infection.
High-risk patients (D+R) remain at risk of developing CMV viraemia and disease after they complete the prophylactic.
Prophylaxis
D+/R- 200 days of valganciclovir.
D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
D-/R- No valganciclovir 4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
Patients with suspected CMV viraemia or disease should have their serostatus (CMV IgG) checked at or around 200 days after starting prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if necessary(2,4,8,12 weeks).
The recipient team will then decide whether the patient should be treated with prophylaxis or not.
What is your analysis regarding the level of evidence, limitations and strengths of Sheffield Protocol? I like your attempt at reflection of your own practice, but it is very fuzzy. I am not sure what your current practice is
serological status of donor and recipient and degree of immunosuppression used are very important to assess risk of CMV disease. Valganciclovir is being used for both prophylaxis and treatment of CMV disease. Duration of prophylaxis also is dependent on serostatus- D+/R- 200 days, D-/R+ & D+/R+ 100 days, 200 days after ATG or Alemtuzumab and D-/R- No valganciclovir. Dose is 900 mg once daily but if renal impairment ten adjustment according to GFR. Routine monitoring is not needed during prophylaxis.
Treatment is indicated if patient is symptomatic or as invasive CMV disease or CMV viral load is greater than 3 logs 10 or rising viral load. Different regimens available: Oral valganciclovir 900mg bd* for 21 days generally in cases where the viral load is >3log10 or have rising titer of CMV viral load and ganciclovir in cases with tissue invasive disease or viral load >4logs10.Dose of valganciclovir is 900mg bd* for 21 days , then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first. IV ganciclovir is administered in a dose of 5mg/kg twice a day for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. Dose adjustment is needed in case of renal impairment.Another regimen is 5mg/kg twice a day of IV ganciclovir for 14-21 days, and continued till 2 x PCR negative
The risk of the disease depend on the serological status of the donor and recipient and intensity of immunosuppression. Valganciclovir is licensed for prophylaxis and treatment of disease
The full prophylaxis dose is 900mg od according to renal profile and is provided for for
1.D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. any patient receiving intensified immunosuppression at any time point beyond 100
Surveillance and testing
Routine surveillance for viraemia is not required. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days started once they finish prophylaxis. CMV PCR on blood is the standard test.
Treatment is applied to
A. Patients that develop viraemia or disease whilst not on prophylaxis irrespective of viral load with reduction in immunosuppression if the viral load is fewer than 3 logs 10 and use valganciclovir if it exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10. IV ganciclovir is indicated in the presence of enteric absorption problem or severe organ involvement
B. Patients that develop viraemia or disease whilst on prophylaxis need consultant virologist decision.
Treatment options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Our local protocol is similar to these recommendations
Please summarise this protocol
Serological status of donor and recipient and degree of immunosuppression used are very important to assess risk of CMV disease. Valganciclovir is being used for both prophylaxis and treatment of CMV disease. Duration of prophylaxis also is dependent on serostatus- D+/R- 200 days, D-/R+ & D+/R+ 100 days, 200 days after ATG or Alemtuzumab and D-/R- No valganciclovir. Dose is 900 mg once daily but if renal impairment ten adjustment according to GFR. Routine monitoring is not needed during prophylaxis.
Treatment is indicated if patient is symptomatic or as invasive CMV disease or CMV viral load is greater than 3 logs 10 or rising viral load. Different regimens available: Oral valganciclovir 900mg bd* for 21 days generally in cases where the viral load is >3log10 or have rising titer of CMV viral load and ganciclovir in cases with tissue invasive disease or viral load >4logs10.Dose of valganciclovir is 900mg bd* for 21 days , then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first. IV ganciclovir is administered in a dose of 5mg/kg twice a day for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. Dose adjustment is needed in case of renal impairment.Another regimen is 5mg/kg twice a day of IV ganciclovir for 14-21 days, and continued till 2 x PCR negative.
Please reflect on your practice
At our center, we follow the similar protocol , Valganciclovir is used in a mini prophylactic dose i.e., 450mg once daily in D+/R+ & D+/R-. and those receiving ATG induction,and continued for 3 months. Treatment is with ganciclovir in cases similar as mentioned above and VGC for mild moderate cases Treatment dose of valganciclovir at our center is 900mg twice a day for 21days or 2 x PCR-01 week apart negative followed by mini-prophylactic dose of VGC.IV ganciclovir is administered in a dose of 5mg/kg twice a day but adjusted according to GFR for 2-3 weeks or 2 x PCR-01 week apart negative.
Sheffield teaching hospital CMV protocol for prophylaxis and treatment of CMV in kidney transplant recipients:
The main principals:
· The donor (D) and recipient (R) serological state decide the risk of CMV disease
· The immunosuppression (IS) strength will decide the risk of disease.
· Valganciclovir (vGCV) is is used in both prophylaxis and disease treatment
· (D+R-) group of patients continue to be at risk of CMV viraemia and CMV disease after the finish taking their .prophylaxis.
CMV prophylaxis:
· Those with (D+/R) will receive 200 days of valganciclovir 900mg OD. Doses are adjusted according to creatinine clearance.
· The D+/R+ and D-/R+ groups will receive 100 days of valganciclovir, but extended to 200 days if they received T cell depleting agents (ATG or Alemtuzumab)
· D-/R- require no prophylaxis
Surveillance and testing by indication in suspected CMV viraemia or disease.
Thresholds for treatment
A. Patients who have viraemia or disease while not on prophylaxis
1.Treatment should be started in all cases of suspected tissue-invasive CMV disease irrespective of viral load.
2. Immunosuppression doses are reduced in R+ patients who have a viral load < 3 logs 10.
3. vGCV treatment is advisable in high-risk group of patients with a viral load > 3 log 10 if they are symptomatic or have a fast rising viral titer.
4. Those with a viral load >4 logs 10, oral vGCV or IV GCV treatment is necessary.
5. IV GCV is advisable in cases when enteric absorption is compromised (diarrhea or vomiting).
6. IV GCV is the drug of choice whenever there is serious organ involvement .However, it is a consultant based decision..
B. Patients that develop viraemia or disease whilst on prophylaxis
1These cases should be discussed with the virologist to set up an optimal treatment plan, as well as to test for drug resistance
Treatment:
There are 3 choices:
· Oral (vGCV) 900mg BD for 21 days, then 900mg OD for 28 days or until 2 negative PCR tests.
· IV (GCV) 5mg/kg BD for 5 days followed by oral (vGCV) 900mg OD until 2 x PCR negative.
· IV (GCV) 5mg/kg BD for 14-21 days, stop date determined by 2 x Pnegative.
Doses of both drugs to be adjusted according to creatinine clearance
Reflection on local practice:
In NHS Grampian we are implementing Edinburgh renal transplantation unit protocol for CMV treatment:
Alternatives include IV Ganciclovir or oral Valgancyclovir
Individual decisions are taken based on the disease severity and viral load
In general, IV Ganciclovir is started initially for 2 weeks followed by oral Valganciclovir and treatment is continued until 2 consecutive negative CMV PCR results are obtained within the same week.
In mild asymptomatic cases or with low viral loads, oral Valganciclovir can substitute IV Ganciclovir
Doses are adjusted according to creatinine clearance
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
· The serological status of the donor and recipient determines the risk of disease
· The intensity of immunosuppression determines the risk of disease.
· Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
· High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule: –
2 weeks –
4 weeks –
8 weeks –
12 weeks
The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised.
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis 1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Our protocol is simillar to it,
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease
. 3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
● D+/R- ==> 200 days of valganciclovir.
●D-/R+ and D+/R+ ==> 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
●D-/R- ==> No valganciclovir
●Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
●The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
■. Routine surveillance for viraemia is not required during prophylaxis
■ D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
■ D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
■CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3 Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients
. 4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10
. 5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
consultant virologist
Treatment
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first.
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Local practice
○Valganciclovir, at least 3 months, for high risk recipients.
Risk factors for CMV infection:
●D+/R-
●R+ receiving ATG or other intense ●immunosuppression treatment or the need of desensitization.
○ Valganciclovir children dose is adjusted depending on BSA.
○ CMV is a widespread virus. Its prevalence is about 100% in Asia compared to 80% in Europe and North America.
==> Only rare cases of R- we will encounter.
○There is no center in our country qualified to perform ABO incompatible renal transplantation.
==> We will not face the need of desensitization in except of pre-transplant blood transfusion and so on.
Treatment
□Ganciclovir 5mg/kg twice a day intravenously for 2- 3 weeks.
□ After 2 week, whole blood QNAT is performed weekly.
□ Treatment will be stopped after two negative QNAT.
□Dose should be adjusted depending eGFR.
◇without rejection ==>reduction of immunosuppression (especially in severe or unresponsive situation.
◇with rejection==> reduction of immunosuppression is challenging. Therefore, decision is made case by case
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at
any time point beyond 100 days
5. The full prophylaxis dose is adjusted according to renal function
*. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of
viral load.
There are three options:
1. Oral valganciclovir
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
CMV prophylaxis
Valganciclovir for 100 or 200 days are prescribed in the following situations:
* Donor Positive or Donors of unknown serostatus to a negative recipients
* recipients positive receiving induction for fear of reactivation
* During a phase of transplant rejection in either positive donor or recipient
* in some centres they use it as a Prophylactic medication against other Herpes viruses
special considerations for Valganciclovir Prophylactic treatment:
Renal adjustment of the dose is mandatory
* calculation of the dose according to body surface area
* in case of development of drug side effects , stopping the drug is required with continuous monitoring of CMV level and preemptive management
Active treatment of CMV
used in the following situations :
* Tissue invasive CMV
* Viral load more than four log
* Titres rapidly rising in high risk patients especially Donor positive recipient negative patients more than three logs
Oral Valganciclovir 900 mg twice daily for three weeks followed by a once daily 900 mg Valganciclovir for four weeks or until we have two successive negative PCR
An Alternative approach I.V Gangiclovir 5 mg/kg twice daily followed by Valganciclovir oral 900 mg once daily until two negative PCR sample
an alternative approach I.V Ganciclovir 5 mg per kilogram for two to three weeks until 2 negative PCR samples .take In consideration the same precautions in dose as in the Prophylactic treatment.
•Consider stopping or at least Reduction of 50 % of dose of MMF
•50 % Reduction of CNI or shift to mTOR.
Reconsider readjusting immunosuppression after cleaning CMV
Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. No surveillance for viraemia during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4- Blood CMV PCR on blood is the standard test.
Thresholds for treatment :
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10
3- Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement.
If the patients develop viraemia or disease whilst on prophylaxis :
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Please summarize this protocol:
CMV prophylaxis depends on CMV serology of the donor and recipient, and the immunosuppression.
D-/R-: no need.
D+/R-: 200 days of Valganciclovir.
D-/R+ and D+/R+: 100days of valganciclovir and 200 days after ATG or Alemtuzumab.
Patients receiving intensified IS at any point after the first 100 days, such as after receiving heavy IS for acute rejection.
Surveillance of CMV:
1- CMV PCR in blood.
2-D+/R- recipients should have their CMV IgG checked at 200 days.
3-D+/R- recipients should start surveillance once they finish prophylaxis.
Treatment thresholds:
1-patients who develop CMV vireamia or CMV disease if they are not on prophylaxis.
2-all cases with tissue invasive CMV disease should be treated.
3-Reduce immune-suppression in R+ with viral load less than 3 logs 10.
4-Use valganciclovir for CMV treatment if CMV viral load above 3 logs 10 if patients are symptomatic or rapidly rising CMV titer.
4-If CMV viral load above 4 logs 10, use IV Ganciclovir or oral valganciclovir.
5-Use IV Ganciclovir in case of severe organ involvement.
6-Regimens available:
A- Oral Val ganciclovir 900mg BD for 3 weeks, then 900mg OD for 4 weeks or until 2 x PCR negative.
B- IV ganciclovir 5mg/kg BD for 5 days followed by oral Val ganciclovir 900mg OD until 2 x PCR negative.
IV ganciclovir 5mg/kg OD for 2-3 weeks, stop date determined by 2 x PCR negative.
Protocol for prophylaxis, surveillance and treatment of CMV after renal transplantation
Principles
The serological status of the donor and recipient determines the risk of disease.
The intensity of immunosuppression determines the risk of disease.
Valganciclovir is licensed for prophylaxis but is often also used for treatment.
High risk patients (D+R-) remain at risk of CMV viremia and disease after they complete the prophylaxis.
Prophylaxis
Prophylaxis should be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days.
The full prophylaxis dose is 900 mg od but there is dose adjustment if there is renal impairment.
D+/R- ; 200 days of valganciclovir.
D-/R+ or D+/R+ ; 100 days of valganciclovir, 200 day after ATG or Alemtuzumab.
D- /R- no valganciclovir
Surveillance and testing by indication in suspected CMV viremia or disease
1.Routine surveillance is not required during prophylaxis.
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viremia or disease is suspected,irrespective on prophylaxis or noyb
Threshold for treatment
1. patients that develop viremia or disease whilst not on prophylaxis
Treatment is mandatory in suspected tissue invasive CMV disease, irrespective of viral load.
Consider reduction in immunosuppression in R+ with a viral load of fewer than 3 log 10
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titer in high risk patients
Consider treatment if the viral load exceeds 4 logs 10
IV Ganciclovir is indicated where enteric absorption is likely to be compromised
IV Ganciclovir is indicated in any patient with severe organ involvement.
2. Patients that develop viremia or disease whilst on prophylaxis
Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment
the choice of oral versus IV therapy is determined by the above mentioned threshold
.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation Principles
. Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed:
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days 3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
as per the following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 weeks
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) .
B. Patients that develop viraemia or disease on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Our institute protocol–
Since almost ( > 90%) all of our transplant are D+R+, we give prophylaxis for 3 month oral valganciclovi,Dose – 450 mg to all ,.and follow with Blood PCR monthly
Treatment-we give oral valganciclovir,usual dose is 450 bd for 21 days unless He/she have severe graft dysfunction –we dont give secondry prophlaxis. We generally reduce dose of immunosuppression by 50%(MMF) and follow with PCR
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the
prophylaxis.
Prophylaxis
200daysofvalganciclovir. 100daysofvalganciclovir,200daysafterATGorAlemtuzumab Novalganciclovir
1. D+/R-
2. D-/R+andD+/R+
3. D-/R-
4. Prophylaxisshouldalsobeconsideredforanypatientreceivingintensifiedimmunosuppressionat
any time point beyond 100 days – Consultant decision.
5. Thefullprophylaxisdoseis900mgodbutnotethatdosereductionforrenalimpairmentis
commonly needed: please consult the Renal Drug Handbook or pharmacist for the appropriate regime and revise in the event of changing renal function.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Page 2 of 3
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g., pneumonitis, encephalitis) – Consultant decision.
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R- ==> 200 days of valganciclovir.
2. D-/R+ and D+/R+ ==>100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use). i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy; please consult the Renal Drug Handbook or pharmacist for an appropriate regime and revise in the event of changing renal function.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases. Additional therapy may be appropriate following the discussion.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles :
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed: please consult the Renal Drug Handbook or pharmacist for the appropriate regime and revise in the event of changing renal function.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days 3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10. Page 3 of 3
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy; please consult the Renal Drug Handbook or pharmacist for an appropriate regime and revise in the event of changing renal function.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases. Additional therapy may be appropriate following the discussion.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the
prophylaxis.
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at
any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is
commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
As per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease
is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or
not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of
viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI
involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis,
encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss
resistance testing
Treatment
The choice of oral versus IV therapy is determined by the above mentioned thresholds and criteria.
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,
whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and
ganciclovir therapy.
reflect on yourpractice.
we follow the almost same protocol.
1- Please summarise this protocol
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at
any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly
needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment:
A. Patients that develop viraemia or disease whilst not on prophylaxis.
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease , irrespective of
viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI
involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis,
encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis:
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss
resistance testing
Treatment:
The choice of oral versus IV therapy is determined by the above mentioned thresholds and criteria.
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR
negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases.
2- Please reflect on your practice:
In our center
1- Risk is determined according sero -status of donor and recipient .
2- Prophylaxis is usually used for 3 months .
3- Serostatus is not checked after completion of prophylaxis course .
4- Q NAT used to diagnose CMV disease.
5- Viral load as a threshold for treatment is not used.
6- Iv gancyclovir or valgancyclovir is used for treatment .
This protocol stated how to prevent, surveillance & treatment of CMV following renal transplantation.
Prophylaxis
Depends on serological status of donor & recipient and intensified immunosuppression.
Preferable drug : valganciclovir 900mg once daily.
1. D+/R- : 200 days following transplantation
2. D-/R+ and D+/R+ : 100 days following transplantation
3. D+/R- : no prophylaxis
4. Intensified immunosuppression during acute rejection at any poin: 100 days.
Surveillance following prophylaxis
D+/R- patient should check CMV IgG at or around 200 days and start surveillance with CMV PCR afer finishing prophylaxis as per following shedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
Threshold for treatment
Treatment is mandatory in tissue- invasive CMV disease
Viral load of fewer than 3 logs 10: appropriate reduction in immunosuppression.
Viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high- risk patient: Treatment with valganciclovir or IV ganciclovir.
Compromise enteric absorption or severe organ involvement(pneumonitis, encephalitis)- IV ganciclovir
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation:
Prophylaxis:
1. D+/R- 200 days of Valganciclovir.
2. D-/R+ and D+/R+ 100 days of Valganciclovir, 200 days after ATG or Alemtuzumab.
3. D-/R- No Valganciclovir.
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viremia or disease:
1. Routine surveillance for viremia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
Following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 week.
4. CMV PCR on blood is the standard test.
Thresholds for treatment:
A. Patients that develop viremia or disease whilst not on prophylaxis:
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease,
irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with Valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titer in high-risk patients.
4. Treatment with Valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be .
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viremia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment.
Drugs treatment:
There are three options:
1. Oral Valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral Valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice:
We are treating CMV disease with ganciclovir. and valganciclovir for prophylaxis of D+/R- patient.
Summary
Introduction
This is a protocol for prophylaxis surveillance and treatment of CMV post kidney transplantation.
Principles
Disease risk is dependent on serological status of both donor and recipient, and the intensity of immunosuppression that is given to the recipient.The drug that is used is valganciclovir. It can be used for both prophylaxis as well as for treatment.The recipient remains at risk of CMV disease even after completing prophylactic treatment, which means that prophylaxis with valganciclovir does not confer unconditional protection to the patient.Prophylaxis
If the donor is positive and recipient negative, then 200 days of valganciclovir.If the donor is negative and recipient is positive, or if both donor and recipient are positive, then 100 days of valganciclovir for former, and 200 days after ATg or alemtuzumab for the latter case.If both donor and recipient are seronegative, then there is no need for valganciclovir.If the patient is receiving IS for more than 100 days, then prophylaxis must be considered irrespective of the serology.Dosage for full prophylaxis is 900 mg OD but dose reduction may be needed depending on kidney function status.Surveillance
Routine surveillance is not required.CMV IgG should be checked at 200 days and once both donor and recipient are finished with prophylaxis.CMV PCR is to be done irrespective of prophylaxis.Treatment thresholds
Treatment is mandatory in all cases of suspicion irrespective of viral load.Reduction in IS is to be considered in seropositive recipients.If patient cannot take oral valganciclovir due to GI involvement, vomiting or diarrhea, then IV valganciclovir is to be given.Treatment
Three options are available :
Oral valganciclovir 900 mg bd for 21 days then 900 mg od for 28 days or until 2 x PCR negative, whichever is first.IV ganciclovir 5 mg/kg bd for 5 days followed by oral valganciclovir 900 mg od until 2x PCR negativeIV ganciclovir 5 mg/kg bd for 14-21 days until 2 x PCR negative.
Practice
Prophylaxis with ganciclovir is done for 100 days in high risk patients such as those donor positive and recipient negative.
Treatment with ganciclovir is done oral for 6 weeks followed by PCR test.
1. Please summarize this protocol
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation at Sheffield Teaching Hospital (NHS)
Date: July 2016 (3rd revision) Review Date: July 2019
Sheffield Kidney Institute Clinical Governance Meeting Date: 18th August 201
Principles
1. Determinant of Risk of CMV infection and disease
o Sero-status of the donor and recipient
o Intensity of immunosuppression
3. Valganciclovir is licensed for prophylaxis, but is also used for treatment of CMV disease.
4. (D+R-) recipients remain at risk of CMV viraemia and disease, even after completion of prophylaxis
Prophylaxis: (Valgancyclovir 900mg OD PO; dose modified as per GFR)
D+/R- given 200 days
D-/R+ and D+/R+ à given 100 days
D-/R+ and D+/R+ receiving ATG / Alemtuzumab induction à 200 days.
D-/R- no prophylaxes.
Surveillance and testing in suspected CMV Viremia or Disease:
1. No Routine surveillance for viraemia during prophylaxis
2. D+/R- patients after completion of 200 days prophylaxis
o To Check serum CMV IgG
o surveillance with CMV PCR at 2 weeks, and monthly for 3months (2-4-8-12weeks)
3. CMV PCR on blood for suspected CMV disease irrespective of being on prophylaxis
Treatment:
Thresholds to decide treatment and regimen
A. CMV viraemia or disease (not on prophylaxis)
1.All cases of tissue-invasive CMV disease
2. Immunosuppression reduction
3. Consider treatment for Symptomatic patients with viremia >3 logs10 or rapidly rising titre
– Treatment is mandatory if viral load exceeds 4 logs 10.
4. IV ganciclovir is indicated if GI involvement (Gastritis, colitis), diarrhoea or vomiting.
5. IV ganciclovir if severe organ involvement (pneumonitis, encephalitis)
Treatment regimen:
Mild cases –
Ø Oral Valganciclovir 900mg bd x 21 days à then 900mg od x 28 days or until 2 x PCR negative
If IV therapy indicated, as per above threshold –
Ø IV ganciclovir 5mg/kg bd x 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
Ø In seriously ill patients: IV ganciclovir 5mg/kg bd x 14-21 days, stop date determined by 2 x PCR negative.
B. Viraemia or CMV disease even on prophylaxis
Ø Treatment with appropriate regimen as per above threshold
Ø Discuss with virologist for best regime and resistance testing
2. Please reflect on your practice:
v We use Valgancyclovir prophylaxes for 8 weeks in all our recipients (Low dose ATG induction 60%, Basiliximab in 40%)
v We don’t have surveillance protocol.
v We hardly see any symptomatic CMV disease
1. Please summarize this protocol;
This is a protocol for prophylaxes, surveillance, and treatment for CMV at NHS.
Prophylaxes;
If D+/R- 200 days valgnciclovir prophylaxes.
If D-/R+ and D+/R+ 100 days valganciclovir, if a patient given ATG or Alemtuzumab given 200 days.
D-/R- no prophylaxes.
Surveillance and testing by indication in suspected CMV viremia or Disease;
For prophylaxes doesnot need monitoring.
For D+/R- patients should be tested for CMV IgG at 200 days.
For D+/R+ patients needed to monitor CMV PCR after 100 days and then at 2, 4, 8 and 12 weeks.
Treatment;
Treatment is mandatory for all suspected cases with symptoms irrespective of viral load.
Immunosuppression modification accordingly.
Consider with initiating valganciclovir when viral load >3 log and if symptomatic and rapidly raising titers.
Consider IV genciclovir when there is compromised absorption, CMV syndrome, already on prophylaxes but developed viremia.
When the choice of treatment if oral valaganciclovir 900mg BD for 21 days, than 900mg OD for next 21 days or until two PCR negative.
If IV ganciclovir 5mg/kg BD for 5 dys then switch to oral valganciclovir 900mg OD until two PCR negative or,
IV ganciclovir 5mg/kg BD for 14 to 21 days/ until 2 PCR negative.
2. Please reflect on your practice;
We use prophylaxes for 100 days in every patients because we have 100% positive patients.
We don’t have surveillance protocol.
We usually treat all patients with disease, syndrome with IV ganciclovir for 21 days, however, if CMV syndrome we continue valganciclovir oral next 100 days without surveillance.
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 weeks
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use)
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
Prophylaxis:
1.D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3.D-/R- No valganciclovir
4.Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
The full prophylaxis dose is 900 mg od but note that dose reduction for renal impairment is commonly needed: please consult the Renal Drug Handbook or pharmacist for the appropriate regime and revise in the event of changing renal function.
Surveillance and testing by indication in suspected CMV viraemia or disease
1.Routine surveillance for viraemia is not required during prophylaxis
2.D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3.D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if required as per the following schedule:
– 2 weeks – 4 weeks- 8 weeks – 12 weeks
The recipient team will coordinate this.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4.Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs10.
5.IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis,encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis
1.Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing Treatment The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.
There are three options:
1.Oral valganciclovir 900 mg bd* for 21 days, then 900 mg od* for 28 days or until 2 x PCR negative,whichever occurs first (off-label drug use).i
2.IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900 mg od* until 2 x PCRnegative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Note that dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy; please consult the Renal Drug Handbook or pharmacist for an appropriate regime and revise in the event of changing renal function.
Virological, pharmacy and other specialist advice should be sought in less straightforward cases.
Additional therapy may be appropriate following the discussion
-In our practice we used extended prophylaxis 200 days for high risk patients( who receive ATG or D+/R- ).
-Treatment is the same as your hospital protocol.
-We didn’t encounter any Ganciclovir resistant cases
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Prophylaxis:
1. D+/R- 200 days of Valganciclovir.
2. D-/R+ and D+/R+ 100 days of Valganciclovir, 200 days after ATG or Alemtuzumab.
3. D-/R- No Valganciclovir.
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viremia or disease:
1. Routine surveillance for viremia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
Following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 week.
4. CMV PCR on blood is the standard test.
Thresholds for treatment:
A. Patients that develop viremia or disease whilst not on prophylaxis:
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease,
irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with Valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titer in high-risk patients.
4. Treatment with Valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be .
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viremia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment.
Drugs treatment:
There are three options:
1. Oral Valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral Valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
We are treating CMV disease with ganciclovir. and valganciclovir for prophylaxis of D+/R- patient.
Prophylaxis
If donor is + and recipient is – prophylaxis will continue for 200 days.
D+\R- or D+\R+ 100 days of valganciclovir
200 days if AaTG or Alemtuzumab is used
No prophylaxis for D-/R-
Prophylaxis should also be considered for any parient given intensified immunosupression even beyond 100 days
CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Surveillance should be done for positive donors and negative recipients once they finish 100 days of prophylaxis.
Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
Treatment options
Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Our Center Protocol
since our all patients are D+\R+ we give them all valganciclovir 450 mg once daily for three months.
out treatment strategy is same like ur hospital
1. Please summarise this protocol
The Sheffield Teaching Hospitals NHS protocol for cytomegalovirus (CMV) post-kidney transplant includes:
1) Prophylaxis: Oral Valganciclovir 900 mg daily (to be adjusted according to creatinine clearance) should be given as prophylaxis for 200 days in D+/R- patients or those who receive ATG or Alemtuzumab, and for 100 days in recipients with a positive serology (D+/R+ or D-/R+). Any patient receiving intensive immunosuppression should be given prophylaxis as per consultant decision.
2) Surveillance: CMV IgG of D+/R- patients should be checked at 200 days post-transplant. Blood CMV PCR should be checked post completion of prophylaxis at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. It should also be done whenever CMV viremia or disease is suspected.
3) Treatment: Treatment should be given in tissue invasive CMV disease, when the viral load is >4 logs 10, rapidly rising titres in high-risk patient (D+/R-), or symptomatic patient with viral loa > 3logs 10. Treatment includes either oral salganciclovir 900 mg BD for 3 weeks, then 900 mg OD for 4 weeks, or until 2 negative blood CMV PCR reports; Intravenous ganciclovir 5 mg/kg BD for 5 days followed by oral valganciclovir 900 mg OD until 2 negative blood CMV PCR reports; or Intravenous ganciclovir 5 mg/kg BD for 2-3 weeks until 2 negative blood CMV PCR reports. Doses need to be adjusted according to the renal function.
2. Please reflect on your practice
In our transplant unit, we use oral valganciclovir as CMV prophylaxis as per the risk category of the recipient.
D+/R- patients are given prophylaxis for 200 days.
D+/R+ patients are given prophylaxis for 100 days.
Patients receiving ATG as induction are given prophylaxis for 100 days.
No surveillance with serology or CMV PCR is done in our unit.
CMV, once diagnosed, is treated with Injection Ganciclovir, till 2 negative CMV PCR reports, at least one week apart.
Summary:
Principles:
· Disease risk is determined by donor and recipient serology as well as intensity of immunosuppression.
· Valganciclovir is used for prevention as well as treatment.
· High-risk individuals (D+R-) remain at risk of CMV viremia and disease despite prophylaxis.
Prophylaxis:
· If D+/R- 200 days valganciclovir prophylaxis.
· If there is D-/R+ and D+/R+ 100 days valganciclovir, 200 days following ATG or Alemtuzumab.
· D- /R- No prophylaxis.
· Consultants should consider prophylaxis for patients receiving increased immunosuppression beyond 100 days.
· The complete prophylaxis dosage is 900mg OD; however, renal impairment requires dose reduction.
Surveillance and testing:
· Prophylaxis does not need viremia monitoring.
· D+/R- patients should be tested for CMV IgG at 200 days.
· D+/R- patients should start CMV PCR monitoring after prophylaxis and then after 2,4,8,12 weeks
Treatment :
· Oral valganciclovir 900mg twice daily for 3 weeks, then 900mg once daily for 4 weeks or until 2 consecutive negative PCR tests whichever is shorter.
· IV ganciclovir 5mg/kg twice daily for 5 days followed by oral valganciclovir 900mg once daily until 2 consecutive negative PCR tests.
· IV ganciclovir 5mg/kg twice daily for 2-3 weeks and stop if 2 consecutive negative PCR tests.
· Dose reduction is needed in compromised renal function.
Please reflect on your practice :
· In our setting all recipients get Valganciclovir prophylaxis (3-6 months) except D-/ R-, which we have not experienced yet.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation Principles
1. The disease risk is determined by the serological status of the donor & recipient and The intensity of IS.
2. Valganciclovir is licensed for prophylaxis and often in treatment of disease.
3. High-risk patients (D+/R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R- (200 days of valganciclovir).
2. D-/R+ and D+/R+ (100 days of valganciclovir, 200 days after ATG or Alemtuzumab).
3. D-/R- (No valganciclovir).
4. Prophylaxis should also be considered for any patient receiving intensified IS at
any time point beyond 100 days (Consultant decision).
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised
6. IV ganciclovir is indicated in any patient with severe organ involvement.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,
whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
Sheffield Kidney Institute CMV protocol (review date 2016)
*** Prophylaxis
Valganciclovir 900 mg od is considered for any +ve D/R CMV between 100-200 days (longer for +/- and severe immunosuppressed)
D-/R- does not require
*** Surveillance
start after finished the antiviral prophylaxis with monitoring CMV PCR on blood after 2-4-8-12 weeks
*** Treatment If a patient develops positive CMV on surveillance, assesses clinically for any symptoms and looks for tissue-invasive CMV disease.
Log < 3: Reduce immunosuppression
Log 3-4: Consider treatment with valganciclovir if symptomatic or rapidly rising titre in high-risk patients
Log > 4: ttt with valganciclovir
IV ganciclovir indicated for:
Regimens:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use)
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Reflection:
nice and clear protocol but I wonder if it needs to be reviewed after the guidelines we had earlier. In practice, I have not exposed to acute transplant yet in my centre
Summary:
· Serological typing by CMV IgG prior to transplantation is essential for risk stratification.
· High risk D+/R-, intermediate risk when R is +ve whatever donor serological status , and low risk when both are negative.
· Prophylaxis by oral valganciclovir differs according to the risk:
o 200 days for high risk.
o 100 days for intermediate risk.
o No prophylaxis in low risk
· Surveillance for CMV viremia: is indicated after the end of 200 days of universal prophylaxis in high risk D+/R-.This surveillance is by CMV PCR in the blood.
· Ttt is indiacted in any conformed tissue invasive disease irrespective to the viral load, and if the viral load is > 5 log 10.
· Ttt can be considered in rising titre of PCR or more than 3 log10 with symptoms.
· IV ganciclovir, rather than oral valganciclovr is indicated in children, severe diases, presence of diarrhea and fear of oral absorption.
· Renal adjustment of the dose according to the GFR is essential.
PROTOCOL FOR CMV PROPHYLAXIS,SURVEILLANCE AND TX POST RENAL TRANSPLANT.
PROPHYLAXIS
1.Donor +VE/Recipient -VE – 200/7 of valganciclovir.
2.Donor -VE/Recipient +VE & Donor +VE/Recipient +VE -100/7 of valganciclovir,200/7 after ATG or Alemtuzumab.
3.Donor -VE/Recipient -ve -No prophylaxis.
4.Any immunosuppressive meds anytime beyond 100/7 is an indication for prophylaxis.
5.Prophylaxis ; 900mg OD, renal dose appropriately esp eGFR <60ml/min.
SURVEILLANCE AND TESTING IN SUSPECTED CMV INFECTION OR DX.
1.During prophylaxis, there’s is no indication for surveillance.
2.D+/R- pts should have CMV IgG done at~200/7.
3.D+/R- pts should be surveilled with CMV PCR after completion of prophylaxis at ~ 2/52,4/52,8/52 and 12/52
4.Whenever CMV infection or dx is suspected do CMV PCR.
THRESHOLDS FOR TX.
A. Pts who get CMV infection with no prophylaxis.
1.Tx indicated in all tx invasive dx irrespective of VL.
2.RIS in R+VE with VL > 3 logs 10.
3.Tx with valganciclovir if VL >3 logs 10 if symptomatic or increasing VL.
4.Tx with valganciclovir or IV ganciclovir if VL > 4 logs 10.
5.In invasive dx with impaired absorption ,give IV ganciclovir.
6.Severe dx with organ involvement e.g pneumonitis or encephalitis is an indication for parenteral tx.
B.Pts that dev infection or dx while on prophylaxis.
1.Consult a virologist ,start tx and consider resistance testing.
TREATMENT.
Options;
1.PO Valganciclovir 900mg BD -21/7 Then 900g OD -28/7 or until x2 negative PCR.
2,IV Ganciclovir 5mg/kg BD -5/7 then PO valganciclovir 900mg OD until x 2 negative PCR.
3.IV Ganciclovir 5mg/kg BD -14-21/7 ,until x2 Negative PCR.
REFLECTION ON PRACTICE;
Lack of funds and resources limits implementation of the protocol in our center.
-For those with dx, we always give PO valganciclovir 900mg BD -21/7 then Maintain at 900mg OD X 3/12
-We don’t routinely give prophylaxis following high dose immunosuppression treatment for rejection.
-Due to again lack of resources, we hardly transplant D+/R- pairs and only consider prophylaxis after ATG tx for rejection.
III. Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation – Sheffield Teaching Hospitals Protocol
Summarise this protocol
Principles
– The donor: recipient CMV serostatus determines the risk of disease.
– The intensity of immunosuppression also determines the risk of CMV disease.
– Valganciclovir is used as prophylaxis as well as treatment of CMV disease
– High-risk patients i.e., (D+/R-) remain at increased risk of CMV viremia and disease even after completing valganciclovir prophylaxis.
Prophylaxis
Surveillance and testing by indication in suspected CMV viremia or disease
– There is no role for routine surveillance for viremia during prophylaxis.
– (D+/ R-) patients should have their CMV IgG status checked at/ or around 200days.
– (D+/ R-) patients should start surveillance with CMV PCR once they finish their prophylactic dose at 2, 4, 8 and 12 weeks.
– The standard test for all transplant recipients is CMV PCR on blood irrespective of whether the patient is on prophylaxis or not.
Thresholds for treatment
– All cases of suspected tissue-invasive CMV disease irrespective of CMV viral load should be initiated on treatment.
– Consider judicious reduction in immunosuppressive therapy in R+ patients with a CMV viral load of less than 3 logs 10.
– Consider initiating treatment with valganciclovir if the CMV viral load is greater than 3 logs 10, if patient is symptomatic or if the CMV viral load titers rise rapidly in high-risk patients.
– When the CMV viral load exceeds 4 logs 10 initiate treatment with valganciclovir or IV ganciclovir.
– In cases where enteric absorption of valganciclovir is compromised (e.g., due to proven GI involvement, vomiting, diarrhoea), IV ganciclovir should be given
– Patients with severe organ involvement e.g., encephalitis, pneumonitis should get IV ganciclovir
– Discuss with the virologist and decide on the appropriate treatment regime as well as discuss resistance testing.
Treatment – three options exist i.e.,
– Oral valganciclovir 900mg BD for 21 days then 900mg OD for 28 days or until the patient attains 2 negative CMV PCR tests whichever comes first
– IV ganciclovir 5mg/kg BD for 5 days then oral valganciclovir 900m OD until the patient obtains 2 negative CMV PCR tests
– IV ganciclovir 5mg/kg BD for 14-21 days, the stop date is dependent on obtaining 2 negative CMV PCR tests
– All ganciclovir and valganciclovir doses should be adjusted as per kidney function
Reflect on your practice
– At our transplant center, we screen for CMV serostatus and risk stratify the donor and recipient.
– We do not routinely offer valganciclovir prophylaxis unless the recipient has received ATG which is also not a common occurrence.
– We also do not offer prophylaxis following intensified immunosuppressive therapy e.g., after rejection.
– Our main drawback is financial constraints – valganciclovir is not affordable to most of our patients neither is routine CMV viral load monitoring
– For patients who have a confirmed diagnosis of CMV disease, we usually give oral valganciclovir 900mg BD for 3 weeks then 900mg OD as secondary prophylaxis for about 3 months.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Serological status of the donor and recipient determines the risk of disease.
Intensity of immunosuppression determines the risk of disease.
High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis:
D+/R- 200 days of valganciclovir 900mg OD depending renal function
D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
D-/R- No need prophylaxis
Surveillance and testing by indication in suspected CMV viraemia or disease:
Routine surveillance for viraemia is not required during prophylaxis
D+/R- should have their serostatus (CMV IgG) checked at or around 200 days
D+/R- should start surveillance with CMV PCR once finish prophylaxis
Thresholds for treatment:
Patients that develop viraemia or disease whilst not on prophylaxis
Treatment is mandatory in all cases of suspected tissue invasive CMV disease, irrespective of viral load.
Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs10.
IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea, or vomiting).
IV ganciclovir is indicated in any patient with severe organ involvement (e.g., pneumonitis, encephalitis) – Consultant decision.
Treatment:
There are three options:
Oral valganciclovir 900mg bd for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use)
IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od* until 2 x CMV PCR negative.
IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
The dose needs renal adjustment in reduced kidney function (CrCL)
In my Practice:
Pre-transplant workup Screening CMV (IgG antibody) for both donors and recipients is considered in our protocol and everywhere.
Prophylaxis is recommended for recipients who received ATG induction or received ATG for Acute Cellular Rejection for six months.
OR when the donor recipient sero- status MM is (D+/ R-) CMV IgG => six months.
Prophylaxis for CMV (D-/R-) with Basiliximab => No prophylaxis needed.
Prophylaxis for CMV (D-/R-) with ATG => six months prophylaxis needed.
Prophylaxis for CMV (D+/R+) with Basiliximab => No prophylaxis needed.
Prophylaxis for CMV (D+/R+) with ATG => six months prophylaxis needed.
Valganciclovir prophylaxis for 6 months following treatment of ACR ttt by ATG.
Dose Adjusted according to Cr CL .
Sheffield teaching hospitals protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation.
Principles of risk assessment
Prophylaxis
Surveillance and testing by indication in suspected CMV viraemia or disease.
Thresholds for treatment
In recipients that develop CMV syndrome or disease whilst not on prophylaxis
1. Treat all suspected tissue invasive CMV disease irrespective of viral load.
2. Consider a reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 with symptomatic infection or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where intestinal absorption is likely to be inadequate (e.g. proven GI disease, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) after discussing with the consultant.
In recipients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment option vis a vis drug resistance testing.
Treatment
In reflecting on my practice;
That quite unique that you never had to treat anyone for CMV
Please summarise this protocol
CMV prophylaxis Vs treatment assessed based on donor/ recipient serology,immunosuppresion protocol, CMV PCR and clinical presentation
Regarding serology
Regarding CMV PCR log and clinical presentation
patient with tissue invasion even with negative serology is indicated for treatment either by gancyclovir or valgancyclovir based on consultant decision especially no risk of disturbed GIT absorption
In my transplant center we used to divide cases into
1. High risk patients (D+ to R-): for such patients we used to give ganciclovir therapeutic dose for 5-7 days post-transplant then switch to valganciclovir therapeutic for 3weaks then prophylactic for 3-6m.
2. Medium risk patient (D+ to R+) who received depleting induction or desensitization we used to give them valganciclovir prophylactic dose for 3-6m post-transplant
3. Low risk patients (D+ to R+) with low immunological risk who didn’t receive depleting induction we follow frequent monitoring of CMV PCR and preemptive treatment.
CMV infection used to treat with ganciclovir in severe cases and valganciclovir in mild cases.
Therapeutic dose continued for at least 2 PCR -ve then switch to prophylactic dose beside decrease immunosuppression to accepted levels according to duration of transplant and severity of infection then switched to prophylactic dose for 6-9m by valganciclovir.
CMV resistance diagnosed by PCR quantitative titer which not responding or increasing although therapeutic optimum ganciclovir dose obtained according to eGFR for such cases we used to give CMV specific IVIG with stop MMF and CNI on the lower level.
I agree that one sould discontinue antimetabolites for few days.
Protocol for prophylaxis, surveillance, and treatment
of CMV after renal transplantation.
CMV Prophylaxis:–
D-/R- No need for Val ganciclovir.
D+/R- using 200 days of Val ganciclovir.
D-/R+ and D+/R+ 100 days of Val ganciclovir and 200 days after ATG or Alemtuzumab.
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days.
5. The full prophylaxis dose is 900mg od and to be adjusted according to RFT.
Surveillance and testing by indication in suspected CMV viraemia or disease.
1-CMV PCR on blood is the standard test for all transplant patients where CMV viremia or disease is suspected.
2-D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
Thresholds for treatment.
A. Patients that develop viremia or disease whilst not on prophylaxis
1.Treatment is mandatory in all cases of suspected tissue-invasive CMV disease.
2.Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with Val ganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with Val ganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
Treatment:-
There are three options:
1. Oral Val ganciclovir 900mg BID for 21 days, then 900mg OD for 28 days or until 2 x PCR negative.
2. IV ganciclovir 5mg/kg BID for 5 days followed by oral Val ganciclovir 900mg OD until 2 x PCR negative.
3. IV ganciclovir 5mg/kg OD for 14-21 days, stop date determined by 2 x PCR negative.
Reflect on your practice:
1-We are using Val ganciclovir as prophylaxis for 100 days and for those high risk or receiving ATG for 200 days.
2-We continue treatment till CMV viral load be undetectable for 2 weeks.
I like you summary, I like that you share your experience
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles
1. The serological status of the donor and recipient determines the risk of disease.
2. The intensity of immunosuppression determines the risk of disease.
3. Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4. High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
1. D+/R-: 200 days of valganciclovir.
2. D-/R+ and D+/R: 100 days of valganciclovir, 200 days after ATG or Alemtuzumab.
3. D-/R- No valganciclovir.
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppressionat any time point beyond 100 days.
5. The full prophylaxis dose is 900 mg OD but note that dose reduction for renal impairment is commonly needed.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis.
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis. This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits as per the following schedule: – 2 weeks – 4 weeks – 8 weeks – 12 weeks.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis:
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis:
· Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy.
I like you summary, I wish you could share your experience and reflect on that
Thank you all
I just wanted to share our protocol with you.
Thnaks Dr Ahmed
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od adjust the dose according to renal function
Surveillance and testing by indication in suspected CMV viraemia or disease:
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease
Thresholds for treatment:
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3.Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist
Treatment:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
in my practice :
used valgancicovir as prophylaxis for 3 month in patient who received ATG as induction therapy
Thank you.
We extend the prophylaxis to 6 months in case of ATG treatment
Principles
1. Disease risk depends on donor and recipient serology.
2. Immunosuppression intensity determines illness risk.
3. Valganciclovir is authorised for prevention but widely used for therapy.
4. High-risk individuals (D+R-) remain at risk of CMV viraemia and infection despite prophylaxis.
Prophylaxis
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od
Surveillance and testing by indication in suspected CMV viraemia or disease
1.During prophylaxis, viraemia surveillance is not required.
2. D+/R- individuals should have their CMV IgG serostatus tested around 200 days.
3. D+/R- patients should start CMV PCR surveillance after prophylaxis. If needed, extra “Bloods and Go” visits to RAU can do this:
2–4–8–12–weeks. The transplant team will coordinate.
4. CMV PCR on blood is the usual test for transplant patients with suspected CMV viraemia or disease, regardless of prophylaxis.
Treatment thresholds
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. All suspected tissue-invasive CMV cases require treatment, regardless of viral load.
2. Lower immunosuppression in R+ patients with virus loads under 3 logs 10.
3. Treat symptomatic or quickly rising titre high-risk patients with valganciclovir if viral load reaches 3 logs 10.
4. Valganciclovir or IV ganciclovir is required for virus loads over 4 logs.
5. IV ganciclovir is recommended for enteric absorption issues (proven GI involvement, diarrhoea or vomiting).
6. Consultant decision: IV ganciclovir for serious organ involvement (e.g. pneumonitis, encephalopathy).
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss treatment options and resistance testing with a consulting virologist.
Treatment
Thresholds and parameters decide oral versus IV therapy.
Three choices:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2x PCR negative, whichever comes first.
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days until 2 x PCR negative
Please reflect on your practice
In my practice we use valganciclovir for prophylaxis and treatment. Prophylaxis is either for 3 or 6 months based on recipients serology.
Thank you.
Please summarise this protocol
Principles
1. The serological status of the donor and recipient, and the intensity of immunosuppression determine the risk of disease.
2. Valganciclovir is licensed for prophylaxis and for the treatment of the disease.
3. After finishing the prophylaxis, high-risk patients (D+R-) continue to be at risk for CMV viremia and disease.
Prophylaxis1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days
5. The full prophylaxis dose is 900mg od but note that dose reduction for renal impairment is commonly needed:
Surveillance and testing by indication in suspected CMV viraemia or disease1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- Patients should begin CMV PCR surveillance as soon as prophylaxis is complete. If necessary, additional “Bloods and Go” visits to RAU can be made in accordance with the following timetable to do, which may be more frequent than clinic appointments:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4. Whether on prophylaxis or not, CMV PCR on blood is the required test for all transplant patients when CMV viraemia or illness is suspected or a possibility in outpatients or inpatients.
Thresholds for treatmentA. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
3. Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis
Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
TreatmentThe choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use)
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
======================================================
Please reflect on your practice
These are comprehensive and reliable guidelines. I can see obvious similarities with our center. ,
During the evaluation of transplantation, CMV serology is routinely done, and those with high clinical suspicion or patients with positive IgM should do PCR.
Patients with detectable viral loads will be given a treatment dose of valganciclovir arranged according to eGFR.
According to CMV determinations and immunosuppression inductions, recipients will be stratified into three groups: low, intermediate, and high risk. The intermediate- and high-risk groups were then given 900 mg OD for three months as prophylaxis.
Follow up clinically and with CBC for side effects.
PCR monitoring is offered every 2 weeks for this period.
Thank you.
This is a protocol of the prophylaxis,surveillance and treatment of CMV after renal transplantation
1.Prophylaxis:
2. Surveillance:
3. When to treat:
A: PCR threshold for treatment
B . Treatment:
Thank you.
The protocol is for the surveillance, prophylaxis and treatment of CMV after renal transplantation
Risk factor for CMV infection include:
Valganciclovir is the drug of choice for prophylaxis. However, it is also used for treatment
It is important to note that CMV infection can occur after completing the prophylaxis, more so for patients at high risk
Prophylaxis
Prophylaxis is with valganciclovir 900 mg once daily (dose adjusted for eGFR) and is between 100 days (D-/R+, D+/R+) or 200 days (D+/R-)
Prophylaxis is also recommended after treatment intensification after rejection episode
Surveillance
Routine surveillance is not recommended during prophylaxis
The serostatus should be checked for all D+/R- patients after completing prophylaxis and these recipients should have surveillance for CMV infection as they are a high risk group
Treatment
Treatment is mandatory for al histologically confirmed invasive disease
In cases of severe disease with organ involvement or inability to retain oral medications, IV ganciclovir should be started
The treatment doses of IV ganciclovir is 5 mg/kg and the dose for valganciclovir is 900 mg twice daily (have to dose adjust as per eGFR)
The treatment should be for a minimum of 2 weeks and after that stopped after getting 2 consecutive undetectable viral load
In Kenya, we do routine surveillance and pre-emptive treatment for CMV due to the high cost of valganciclovir. After treatment for ABMR or ACR, we do surveillance and pre-emptive treatment.
For patients who develop CMV disease, we treat with IV ganciclovir for 5 days then with valganciclovir if the patient is able to take orally
Thank you.
I like your summary of these guidelines. I like your reflection of current practice in Kenya
■ Sheffield Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
● prophylaxis of CMV after renal transplantation :
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
4. patient receiving intensified immunosuppression at any time point beyond 100 days
5. prophylaxis dose is 900mg od adjusted for renal function
● Surveillance in CMV viraemia or disease
1. Routine surveillance is not required during prophylaxis
2 . CMV IgG at 200 days in D+/R- patients
3 . CMV PCR at the end of prophylaxis in D+/R- patients
4. CMV PCR on blood is the standard test for all transplant patients
● Thresholds for treatment
☆ Viraemia or disease developing whilst not on prophylaxis
1. In case of suspected tissue-invasive CMV disease treatment is mandatory in all irrespective of viral load.
2. IR in R+ patients with a viral load < 1000
3. Valganciclovir when viral load > 1000 if symptomatic or high-risk patients.
4. Valganciclovir or IV ganciclovir is mandatory when viral load > 10000
5. IV ganciclovir in proven GI involvement
6. IV ganciclovir in severe organ involvement (pneumonitis, encephalitis)
☆ Viraemia or disease developing whilst on prophylaxis
1. A consultant virologist to agree best treatment regime and discuss resistance testing
● Treatment
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
* Dose adjustment for renal function
● In our practice we use valgancyclovir for prophylaxis for 3 – 6 months in these cases :
▪︎D+/R-
▪︎T cell depleting agents
☆ treatment with valgancyclovir for CMV disease or viremia except
when there is diarrhoea or vomiting or severe involvement (pneumonitis, encephalitis) then we use IV gancyclovir
I like your summary of these guidelines. I wish you could write reflection of current practice in your hospital
Prophylaxis:
Determine serological status of D/R and intensity of IS:
– D+/R- 200 days of valganciclovir.
– D-/R+ & D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
– D-/R- No valganciclovir
– After receiving intensified IS at any time point.
-the dose should be adjusted for renal impairment is
Surveillance and testing;
– Routine surveillance is not required during prophylaxis
– D+/R- ; check CMV IgG & CMV PCR once they finish prophylaxis.
– CMV PCR checked in all suspected CMV viremia or disease.
Thresholds for treatment
A.CMV viraemia or disease whilst not on prophylaxis
– All cases of invasive CMV should be treated irrespective of viral load.
– Viral load < than 3 logs 10; reduce immunosuppression
– Viral load > 3 logs 10 or if symptomatic or rapidly rising titre ; treat with valganciclovir.
– Viral load > 4 logs 10 ; Treat with oral valganciclovir or IV ganciclovir.
-IV ganciclovir used if severe organ involvement or if enteric absorption reduced.
B. CMV viraemia or disease whilst on prophylaxis
– Cases should be discussed with a consultant virologist to agree treatment regime and discuss
resistance testing
Treatment
– Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,
whichever occurs first
– IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
– IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
In our center;
Majority of our patients D+/R- ( pediatric ), prophylaxis given for all 3-6 months.
For treatment; we treat similar to this protocol.
I like your summary of these guidelines. I like your reflection of current practice in your hospital
Please summarise this protocol
The serological status of the donor and recipient determines the risk of disease
The intensity of immunosuppression determines the risk of disease
Valganciclovir is licensed for prophylaxis but can be used for the treatment of disease
(D+R-) remain at risk of CMV viraemia and disease after prophylaxis.
Prophylaxis
· D+/R- 200 days of valganciclovir.
· D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
· D-/R- No valganciclovir
· Prophylaxis for any patient receiving intensified immunosuppression at any time point beyond 100 days
· The full prophylaxis dose is 900mg od adjust dose in renal impairment
Surveillance and testing by indication in suspected CMV viraemia or disease
· Routine surveillance for viraemia is not rneeded during prophylaxis
· D+/R- should have CMV IgG checked at or around 200 days
· D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
· Extra “Bloods and Go” visits at – 2 weeks – 4 weeks – 8 weeks – 12 weeks
· CMV PCR on blood is the standard test when CMV viraemia or disease is suspected
Threshold for treatment
Patients that develop viraemia or disease whilst not on prophylaxis
· Suspected tissue-invasive CMV disease
· valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre
· IV ganciclovir is indicated where enteric absorption is an issue
· IV ganciclovir in systemic tissue involvement
Development of viraemia or disease whilst on prophylaxis
Treatment
Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative
IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative
IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice
We give CMV prophylaxis to those having ATG for 3 months
I like your summary of these guidelines. I like that you have reflected of current practice in your hospital, but typing just one sentence is not good enough.
Serological status of the donor and recipient determines the risk of disease.
Intensity of immunosuppression determines the risk of disease.
High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis:
Surveillance and testing by indication in suspected CMV viraemia or disease.
Thresholds for treatment
Treatment
There are three options:
The dose need renal adjustment in reduced kidney function
I like your summary of these guidelines. I wish you could write reflection of current practice in your hospital
Please summarise this protocol
*Principles:
1) The serological condition of both donor (D) and recipient (R) decide the risk of disease.
2) The strength of immunosuppression (IS) deciding the risk of disease.
3) Valganciclovir (vGCV) is permitted as prophylaxis; however, can be used for treatment.
4) High-risk patients (D+R-) still at risk of CMV viraemia and disease after they finish the prophylaxis.
*Prophylaxis
1) D+/R- 200 days of (vGCV).
2) D-/R+ and D+/R+ 100 days of (vGCV), 200 days after ATG or Alemtuzumab
3) D-/R- without (vGCV).
4) Consultation is recommended for any patient receiving heavy IS at any time point beside 100 days.
5) Complete prophylaxis dose is 900 mg OD; however, the dose should be reduced in case of renal impairment.
*Surveillance and testing by indication in suspected CMV viraemia or disease
1) Routine surveillance for viraemia is not need during prophylaxis
2) D+/R- patients should monitor (CMV IgG) at 200 days
3) D+/R- patients must start monitoring with CMV PCR after they complete the prophylaxis.
Extra “Bloods and Go” visits to RAU if required as per the following schedule: ( 2 weeks, 4 weeks, 8 weeks, 12 weeks).The recipient team will coordinate this.
4) Blood CMV PCR is the definitive test for CMV viraemia or disease in all suspected patients regardless on prophylaxis or not.
*Thresholds for treatment
A. Viraemia or disease in non prophylactic patients:
1) Treatment is necessary in all suspected cases of tissue-invasive CMV disease, in spite of viral load.
2) Recommended suitable reduction in IS in R+ patients with a viral load of less than 3 logs 10.
3) Advised treatment with (vGCV) when the viral load above 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
4) Treatment with (vGCV) or IV ganciclovir (GCV) is necessary when the viral load above 4 logs 10.
5) IV (GCV) is advised where enteric absorption is likely to be compromised.
6) IV (GCV) is advised in severe organ involvement, and it is a consultant decision.
B. Viraemia or disease in prophylactic patients:
1. The consultant virologist should agree a better treatment regime and the resistance testing.
*Treatment:
*The option of oral or IV therapy is based on the above mentioned thresholds and criteria.
*There are (3) options:
1) Oral (vGCV) 900mg BD for 21 days, then 900mg OD for 28 days or until 2 negative PCR tests.
2) IV (GCV) 5mg/kg BD for 5 days followed by oral (vGCV) 900mg OD until 2 x PCR negative.
3) IV (GCV) 5mg/kg BD for 14-21 days, stop date determined by 2 x PCR negative.
*** Dose reductions of both (vGCV & GCV) is recommended in renal impairment.
# Please reflect on your practice
Cytomegalovirus prophylaxis is recommended for:
(1)Patients who received ATG induction; (high to moderate risk)
(2)Patients who are CMV-IgG negative and received kidneys from CMV-IgG positive donor. The preferred agent is valganciclovir for 3 months.
I like your summary of these guidelines. I like your reflection of current practice in your hospital
Thanks alot prof Ajay
1. Please summarise this protocol
1.The risk of disease is determined by the serological status of the donor & recipient.
2. The risk of disease is influenced by the degree of IS.
3. Although valganciclovir is licensed for prophylaxis, it is used for treatment as well.
4. After completing the prophylaxis, high-risk patients (D+R-) continue to be at risk for CMV viraemia & illness.
Prophylaxis duration
1. D+/R- 200 days.
2. D-/R+ & D+/R+ 100 days, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Any patient on enhanced IS at any time point after 100 days should also be considered for prophylaxis, according to consultant decision.
5. The prophylaxis dose is 900mg od; dose reduction for renal impairment is needed: Renal Drug Handbook or pharmacist consultation.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. During prophylaxis, routine viraemia surveillance is not required.
2. At or close to 200 days, D+/R- patients should have CMV IgG tested.
3. D+/R-: start surveillance with CMV PCR once prophylaxis finished. This may be more frequent than clinic visits:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
4. CMV PCR on blood is the standard test where CMV viraemia or disease is suspected irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients who have viraemia or disease while not on prophylaxis
1. Treatment in all suspected tissue-invasive CMV disease, irrespective of viral load.
2. IS dose reduction in R+ patients with a viral load of fewer than 3 logs 10.
3. Valganciclovir treatment is necessary if a high-risk patient’s viral load > 3 log 10 & are symptomatic or a fast increasing viral titre.
4. When the viral load surpasses 4 logs 10, valganciclovir or IV ganciclovir treatment is required.
5. Where enteric absorption is compromised(proven (GI upset, diarrhoea or vomiting), IV ganciclovir is recommended.
6. Any patient with serious organ involvement (pneumonitis or encephalitis) should get IV ganciclovir, as determined by the consultant.
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss the optimal treatment plan, as well as resistance testing, with a virologist.
Treatment
Options:
1. Oral valganciclovir 900mg bdx21 days, then 900mg od x 28 days or until 2 x PCR-neg.
2. IV ganciclovir 5mg/kg bdx5 days then oral valganciclovir 900mg od until 2 x PCR-neg.
3. IV ganciclovir 5mg/kg bdx14-21 days, stop date established by 2-neg PCR results.
N.B: dose reductions for renal impairment are needed with valganciclovir & ganciclovir
==============================
2. Please reflect on your practice
In our facility, valaganciclovir is given to high- to moderate-risk TX patients who are receiving ATG as induction therapy. Instead of the 200 days specified in these standards, we give it for 90 days only due to financial issues.
I like your summary of these guidelines. I like your reflection of current practice in your hospital
I- Prophylaxis:
Prophylaxis depends on the serostatus of both DC and R and the severity of IS:
II- Surveillance and testing in suspected viraemia or disease:
-Should have their serostatus (CMV IgG) checked at or around 200 days
– Should start surveillance with CMV PCR once they finish prophylaxis.
III- Threshold for treatment for patients eveloped viraemia or disease:
a- Patients not on prophylaxis:
b- Patients on prophylaxis:
MDT with virologist for the proper treatment and resistance testing.
IV- Treatment:
I like your summary of these guidelines. I wish you could write reflection of current practice in your hospital
Summary
Prophylaxis is indicated according to the risk (serological status and intensity of IS)
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Based on consultant decision, Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days.
5. The full prophylaxis dose is 900mg od dose should be adjusted according to the creatinine clearance
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3 surveillance with CMV PCR once they finish prophylaxis should be started in D+/R- patients with more frequent than clinic visits and can be achieved with extra “Bloods and Go” at: – 2 weeks – 4 weeks – 8 weeks – 12 weeks The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. if the viral load of fewer than 3 logs 10, Consider appropriate reduction in immunosuppression in R+ patients with
3. If the viral load exceeds 3 logs 10 Consider treatment with valganciclovir when symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) or where in GIT involvement where absorption is likely to be affected
B. Patients that develop viraemia or disease whilst on prophylaxis case should be discussed individually consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).i
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative. 3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
I like your summary of these guidelines. I wish you could write reflection of current practice in your hospital
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation:
factors that determine of risk categorizations:
1.serological status of both D& R ( D+/ R- high risk , D+/R+ ,D-/R+ moderate risk, D-/R- low risk)
2.intensity of immunosuppressive medications at induction, maintenance & treatment of rejection episodes (alemtuzumab & ATG)
PROPHYLAXIS:
A. Medications such as valganciclovir and ganciclovir
B.Indications & durations: dosage 900 mg but require dose adjustment if renal impairment
1.high risk ……200 days
2.moderate risk …..100 days ,if after intensive immunosuppressive…..extended to 200 days
3.low risk …no need
note: high risk group remain risk of infection after prophylaxis has been finished
SURVEILLANCE:
A. during prophylaxis….. no need routinely but high risk ones require at the end of prophylaxis duration
B. after prophylaxis ……schedules at 2 weeks,4 weeks,8 weeks and 12 weeks
note: the standard investigation is CMV PCR on blood sample
Treatment :
A. when developing infection or disease while on prophylaxis:
required an MDT discussion with virologist and focus on work ups for identifying resistance strains
B. while not on prophylaxis
RX. ROUTE & DURATION:
either oral valganciclovir or IV ganciclovir
different duration protocols available ….generally for several weeks until 2 PCR will be negative
I like your summary of these guidelines. I wish you could write reflection of current practice in your hospital
Please summarise this protocol
Protocol for prophylaxis, surveillance, and treatment of CMV after reanl transplantation- Sheffield Teaching Hospital.
Principles
The donor and recipient serological status determines the risk of disease, as well as the immunosuppression used.
Valgancyclovir is licensed for prophylaxis, but often used for treatment.
High risk donor +/ recipient – remains at risk of CMV viremia even after completion of prophylaxis.
Prophylaxis
Surveillance and testing by indication in suspected CMV viraemia or disease
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis:
B. Patients that develop viraemia or disease whilst on prophylaxis:
Treatment options
Virological, pharmacy and other specialist advice should be sought in less straightforward cases. Additional therapy may be appropriate following the discussion.
Please reflect on your practice
In our practice we use not to routinely monitor PCR, we use to order it when viremia or disease is suspected.
We use to give valgancylovir prophylaxis for 6 months for all high risk groups as forementioned, and for 3 months for the low risk groups.
The treatment protocol we use is 5 days if IV gancyclovir followed by oral valgancyclovir until x2 PCR negative.
I like your summary of these guidelines. I like your reflection of current practice in your hospital
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation:
Aim of prophylaxis:
Prophylaxis :
Patients with positive donor and negative recipient or both positive for prophylaxis 200 days.
Patients negative donor and positive recipient or both positive for 100 days valganciclovir.
Patients receive ATG or Alemtuzumab for prophylaxis 200 days.
Also prophylaxis for 100 days given to all patients receive intense immunosuppressive therapy.
Recommended dose is valganciclovir 900 mg and need dose adjustment in case of renal impairment.
Surveillance:
Monitoring of CMV by CMV igG test for 200 days in case of positive donor and negative recipient.
Positive donor and negative recipient should start serial monitoring of CMV PCR every 2wk/ 4wk/ 8wk and 12wk.
CMV PCR is the test for diagnosis of all transplanted patients with CMV viremia and disease.
Thresholds for treatment:
If patient develop viremia while in prophylaxis should refer and discuss with infectious consultant.
Treatment:
Oral valganciclovir 900mg twice a day for 21 days, then 900mg once a-day for 28 days or until 2 x PCR negative.
2. IV ganciclovir 5mg/kg twice a day for 5 days followed by oral valganciclovir 900mg once a day until 2 x PCR negative.
3. IV ganciclovir 5mg/kg twice a day for 14-21 days, stop date determined by 2 x PCR negative.
We use prophylaxis of ganciclovir same as this protocol
I like your summary of these guidelines. I like that you have reflected of current practice in your hospital, but typing just one sentence is not good enough.
Protocol for prophylaxis, surveillance, and treatment of CMV after
renal transplantation
Principles
1. The risk of illness depends on the serological status of the donor and recipient.
2. The risk of disease is influenced by the degree of immunosuppression.
3. Although valganciclovir has a license for prophylaxis, it is frequently utilized for illness treatment as well.
4. After finishing the prophylaxis, high-risk patients (D+R-) continue to be at risk of CMV viraemia and illness.
Prophylaxis;
1. 200 days of valganciclovir therapy.
2. 100 days after valganciclovir, 200 days after ATG, and D-/R+ and D+/R+
3. No valganciclovir in D-/R-
4. Any patient getting enhanced immunosuppression at any time point after 100 days should also be given consideration for prophylaxis, according to consultant opinion.
5. The complete prophylactic dose is 900 mg od, however it should be noted that dose reduction for renal impairment is frequently required; for the proper regimen and to be revised in the case of altered renal function, consult the Renal Drug Handbook or your pharmacist.
Surveillance and testing by indication in suspected of CMV virimia or disaease
1. During prophylaxis, routine viraemia surveillance is not necessary.
2. At or close to 200 days, D+/R- patients should have their serostatus (CMV IgG) tested.
3. After completing prophylaxis, D+/R- patients should begin surveillance with CMV PCR. If necessary, additional “Bloods and Go” visits to RAU might be made in accordance with the following timetable to do this, which might be more frequently than clinic visits.
– 2 weeks, 4 weeks, 8 weeks and 12 weeks
4. Whether or whether prophylaxis is being taken, CMV PCR on blood is the routine test for all transplant patients when CMV viraemia or illness is suspected or a possibility in outpatients or inpatients.
Threshold of treatment
Patients that develop viraemia or disease whilst not on prophylaxis
1. Regardless of viral load, treatment is required in all suspected tissue-invasive CMV illness cases.
2. For R+ patients with a viral load of under 3 logs 10, suitable immunosuppressive decrease should be considered.
3. When the viral load in high-risk patients exceeds 3 logs 10 and they are symptomatic or their viral titre is rising quickly, consider starting valganciclovir treatment.
4. When the viral load exceeds 4 logs 10, valganciclovir or IV ganciclovir treatment is required.
5. Where enteric absorption is likely to be limited (proven GI problems, diarrhoea or vomiting), IV ganciclovir is suggested.
6. Any patient with serious organ involvement (such as pneumonitis or encephalopathy) requires IV ganciclovir, as determined by the consultant.
Treatment
The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.
There are three options:
1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative,
whichever occurs first (off-label drug use). I
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR
negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please be aware that dose reductions for renal impairment are frequently required while using valganciclovir and ganciclovir therapy; for an appropriate regimen, check the Renal Drug Handbook or your pharmacist, and make any necessary revisions if your kidney function changes.
In less straightforward circumstances, it is advisable to seek the counsel of specialists in virology, pharmacy, and other fields.
After the discussion, additional counseling may be necessary.
Our practice reflect the same as guilines.
I like your summary of these guidelines. I like your reflection of current practice in your hospital. ‘Guidelines’ got mistyped as ‘guilines’ in last line. .
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles
The donor and recipient serological status and intensity of immunosuppression determines the disease risk.
Valganciclovir is licensed for prophylaxis and treatment.
High-risk patients (D+R-) remain at risk after completing prophylaxis.
Prophylaxis
D+/R- 200 days of valganciclovir.
D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab.
D-/R- No prophylaxis.
Consider prophylaxis after a period of intense immunosuppression.
The dose is 900mg od, adjusted according to renal function.
Surveillance and testing by indication in suspected CMV viraemia or disease
No surveillance during prophylaxis.
Check serostatus around 200 days in D+/R- patients and start surveillance at 2, 4, 8 and 12 weeks after completing prophylaxis.
Blood CMV PCR is the standard test where viraemia is suspected.
Thresholds for treatment
Patients not on prophylaxis
Treat all suspected tissue-invasive disease, irrespective of viral load.
Consider IS reduction in R+ patients with a viral load of < 3 logs.
Consider treatment when viral load> log 4 or > log 3 if symptomatic or rapidly rising titre in high-risk patients.
Consider IV ganciclovir in severe organ involvement or when enteric absorption is compromised.
Patients on prophylaxis
Discuss all cases with a virologist, consider resistance testing
Treatment
There are three options:
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative.
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd for 14-21 day until 2 x PCR negative.
Our centre is more or less the same except that after the prophylaxis period, we monitor CMV monthly for the first year after transplant.
I like your summary of these guidelines. I like your reflection of current practice in your hospital.
Please summarise this protocol
Principles
-The serological status and intensity of immunosuppression determine the risk of disease.
-Valganciclovir is lused for prophylaxis and treatment of disease.
-D+/R- remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis
-D+/R- 200 days of valganciclovir.
– D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
– D-/R- No valganciclovir
-The full prophylaxis dose is 900mg od but adjust the dose according to renal impairment.
Surveillance and testing by indication in suspected CMV viraemia or disease
-Routine surveillance for viraemia is not required during prophylaxis.
-D+/R- patients should have their serostatus checked at or around 200 days.
-D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
– CMV PCR on blood is the standard test for all transplant patients.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
-Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
-Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
-Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
-Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
-IV ganciclovir is indicated where enteric absorption is likely to be compromised .
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment
-The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria.
There are three options:
– Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative .
– IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative.
-IV ganciclovir 5mg/kg bd for 14-21 days, stop date determined by 2 x PCR negative.
Please reflect on your practice
-In our center, we screen the donor and recipient pre-transplant.
-We transplant D+/R+ or D-/R+, so we give valganciclovir prophylaxis dose for 100 days.
-In treatment, we use either valganciclovir or ganciclovir therapy.
I like your summary of these guidelines. I like your reflection of current practice in your hospital.
Summary of the protocol of prophylaxis, surveillance, and treatment of CMV after renal transplantation:
Principle:
Prophylaxis:
Surveillance and testing by indication in suspected CMV viremia or disease
The recipient team will coordinate this.
4.CMV PCR in the blood is the standard test for all transplant patient where CMV viremia or disease is suspected or a possibility in outpatient and inpatient, irrespective of whether on prophylaxis or not.
Threshold for treatment:
A. patient that develops viremia or disease whilst not on prophylaxis;
B. patients that develop viremia or disease whilst on prophylaxis:
Treatment:
The choice of oral vs IV therapy is determined by the above-mentioned threshold and criteria; there are three options:
Adjust the dose according to the kidney function.
Local practice:
I like your summary of these guidelines. I like that you have reflected of current practice in your hospital, but typing just 4 words in this heading is not good enough.
Please summarise this protocol
This is Sheffield teaching hospitals protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation, July 2016 (3rd revision), reviewed July 2019
*The risk of diseases is determined by:
1. Serostatus of the donor and recipient
2. Intensity of immunosuppression
*Valganciclovir is for prophylaxis and treatment
*The risk is still there after complete prophylaxis in high risk patients (D+R-)
Prophylaxis (indications and duration)
Valganciclovir with a dose of 900mg (with dose reduction for renal impairment)
Indications include:
1. D+/R- (200 days)
2. D-/R+ and D+/R+ (100 days of valganciclovir, 200 days after ATG or Alemtuzumab)
3. Intensive immunosuppression at any time point beyond 100 days (Consultant decision)
No prophylaxis in D-/R-
Surveillance (CMV IgG and CMV PCR)
Routine surveillance is not required during prophylaxis
D+/R- : check serostatus (CMV IgG) at or around 200 days
D+/R- : once they finish prophylaxis, with CMV PCR (2 weeks – 4 weeks – 8 weeks – 12 weeks)
CMV PCR on blood is the standard test where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not
Treatment threshold
viraemia or disease whilst not on prophylaxis
*Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load
*Reduce immunosuppression in R+ with a viral load of < than 3 logs 10
* Valganciclovir when the viral load > 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients
*Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10
*IV ganciclovir is indicated when enteric absorption problem (proven GI involvement, diarrhoea or vomiting)
*IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision
viraemia or disease whilst on prophylaxis
*Discuss all such cases with a consultant virologist
Treatment
Options include (oral versus IV therapy is determined by the abovementioned thresholds and criteria):
1. Oral valganciclovir 900mg bd for 21 days, then 900mg od for 28 days or until 2 x PCR negative, whichever occurs first
2. IV ganciclovir 5mg/kg bd for 5 days followed by oral valganciclovir 900mg od until 2 x PCR negative
3. IV ganciclovir 5mg/kg bd for 14-21 days (stop date determined by 2 x PCR negative)
Please reflect on your practice
We do not give prophylaxis (most patients are D+/R+). Management depends on clinical suspicion, viral load, and histopathology. We give valganciclovir for treatment (no viral load monitoring). No post transplant survey and pre-emptive treatment
I like your summary of these guidelines. I like your reflection of current practice in your hospital.
Perhaps you wanted to type ‘No post transplant surveillance’ rather than ‘No post transplant survey’.
Please summarise this protocol :
1- D-/R- …….. No prophylaxis with valganciclovir is needed.
2- D+/R- …….. prophylaxis is needed with Valganciclovir for 200 days to # 1ry infection.
3- R+ with any donor ….. prophylaxis is needed with Valganciclovir for 100 days, 200 days after ATG or Alemtuzumab
NB1. Prophylaxis should also be considered for any patient receiving intensive immunosuppression at any time after 100 days
NB2. The usual prophylaxis dose is 900 mg od with dose reduction in CKD.
1- D+/R- …..
a- Check CMV IgG at 6 months.
b- Check CMV PCR at the end of prophylaxis and then after 2,4,8,12 weeks
1- Oral valganciclovir 900mg twice daily for 3 weeks, then 900mg once daily for 4 weeks or until 2 consecutive negative PCR tests whichever is shorter.
2- IV ganciclovir 5mg/kg twice daily for 5 days followed by oral valganciclovir 900mg once daily until 2 consecutive negative PCR tests.
3- IV ganciclovir 5mg/kg twice daily for 2-3 weeks and stop ttt if 2 consecutive negative PCR tests.
Please reflect on your practice :
I like your summary of these guidelines. I like your reflection of current practice in your hospital.
Thank you Prof. Ajay
CMV infection is commonly encountered in the context of renal transplantation with detrimental consequences and heightened mortality and morbidity. The guideline advocates prophylactic protocol depending on risk factor determined by virology status and intensity of immunosuppression therapy.
Therefore, in status of D+/R- which is the riskiest setting for attracting CMV infection, valgranciclovir is implemented prophylactically for 200 days. Nevertheless, risk of infection is still significant post prophylactic, and having CMV PCR status checked is indicated post prophylaxis on regular basis, after having CMV IgG status scrutinized towards end of prophylaxis period.
Valganciclovir 900 mg per day is drug of choice for prophylaxis and treatment.
in other status of sero-positivity D-/R+ and D+/R+ a prophylaxis course of 100 days is warranted, except when lymphocytes depleting agent ATG or Alemtuzumab was used, then similar course of 200 days prophylaxis is indicated.
in D-/R- sero-status, no prophylaxis protocol is indicated .
Treatment is indicated for all invasive CMV infection regardless to viral load.
reduction of immunosuppression is indicated when viral load is less than 3 log 10.
More than 3 log 10 or rising titer Valganciclovir is considered.
More than 4 log 10 Valganciclovir is mandatory.
What is 3 or 4 log 10? Why not log 3 or 4?
Principles
1. Donor and recipient serology determine illness risk.
2. Immunosuppression intensity determines illness risk.
3. Valganciclovir is authorized for prevention but widely used for therapy.
4. High-risk individuals (D+R-) remain at risk of CMV viremia and illness despite prophylaxis.
Prophylaxis
D+/R- 200 days valganciclovir.
2. D-/R+ and D+/R+ 100 days valganciclovir, 200 days following ATG or Alemtuzumab
3. D- /R- Valganciclovir-free
4. Consultants should consider prophylaxis for patients receiving increased immunosuppression beyond 100 days.
5. The complete prophylaxis dosage is 900mg OD; however, renal impairment sometimes requires dose reduction.
Suspected CMV viremia or illness surveillance and testing.
1. Prophylaxis does not need viremia monitoring.
2. D+/R- patients should be tested for CMV IgG at 200 days.
3. D+/R- patients should start CMV PCR monitoring after prophylaxis. If needed, more “Bloods and Go” trips to RAU may do this:
2–4–8–12–weeks
The receiving team will coordinate.
4. All transplant patients with suspected CMV viremia or illness have a blood CMV PCR.
Treatment thresholds
non-prophylactic patients with viremia or illness.
1. All suspected tissue-invasive CMV cases need treatment, regardless of viral load.
2. Lower immunosuppression in R+ patients with virus loads under 3 logs. 10.
3. Treat viral loads above 3 logs with valganciclovir. 10 if high-risk or symptomatic.
4. Valganciclovir or IV ganciclovir is required when the viral load reaches 4 logs.
10.
5. In cases of GI involvement, diarrhea, or vomiting, IV ganciclovir is recommended.
6. Consultant decision: IV ganciclovir for serious organ involvement (e.g., pneumonitis, encephalopathy).
Prophylaxis patients with viremia or illness
1. Discuss all cases with a specialist virologist to determine the optimal therapy and resistance testing.
Treatment Based on the above thresholds and criteria, the choice between oral and IV therapy is made.
There are three options:
1. Valganciclovir 900 mg bd* for 21 days, then 900 mg od* for 28 days, or until two PCR tests are negative, whichever comes first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
We are consulting the ID team for any case of CMV disease, and they are nearly following the same lines of treatment.
Regarding the prophylaxis: all our patients receive prophylaxis for 3 months except D+ to R-VE and the patient who received ATG. We are extending the prophylaxis to 6 months.
I like your summary of these guidelines. I like your reflection of current practice in your hospital.
Principles;
—————————-
1-The serological status of the donor and recipient determines the risk of disease.
2-The intensity of immunosuppression determines the risk of disease.
3-Valganciclovir is licensed for prophylaxis but is often also used for the treatment of disease.
4-High-risk patients (D+R-) remain at risk of CMV viraemia and disease after they complete the prophylaxis.
Prophylaxis;
—————————————
1-low risk group (D-/R-)
no need to give valganciclovir .
2-Intermediate risk group (D-/R+ and D+/R+)
100 days of valganciclovir .
3-High risk group (200 days Valganciclovir)
a- D+/R- .
b- Intermediate risk groups ,if they received T-cell depleting agent .
4-Those,who received intensified immunosuppressant ; Prophylaxis should be considered .
5-The standard adult prophylactic dose is 900 mg od and the dose should be adjusted according to the creatinine clearance in case of renal impairment .
Surveillance and testing by indication in suspected CMV viraemia or disease;
———————————————————————————————————
1-Survveillance for viraemia is recommended in the following groups o patients ;
a- D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days.
b- D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
This may be more frequent than clinic visits and can be achieved with extra “Bloods and Go” visits to RAU if
required as per the following schedule:
– 2 weeks
– 4 weeks
– 8 weeks
– 12 weeks
The recipient team will coordinate this.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment;
——————————————————————————————-
A-Patients that develop viraemia or disease whilst not on prophylaxis;
1-Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2-According to the viral load consider the following ;
A-reduction o immunosuppression ,if the viral load is of less than 3 logs 10.
B-Valganciclvir ,if ;
The viral load exceeds 3 logs 10 .
symptomatic .
rapidly rising titre in high-risk patients.
C-Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
3. IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
4. IV ganciclovir is indicated in any;
A- patient with severe organ involvement (e.g. pneumonitis, encephalitis) – Consultant decision.
B. Patients that develop viraemia or disease whilst on prophylaxis.
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment;
——————————————–
The choice of oral versus IV therapy is determined by the above mentioned thresholds and criteria.
There are three options:
1-Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2-IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3-IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Please note dose reductions for renal impairment are commonly needed with valganciclovir and ganciclovir therapy .
Please reflect on your practice;
———————————————————–
We do not routinely screened recipient unless there a clinical suspicion.
Oral valganciclovir is recommended for prophylaxis in high risk patient and mild disease . Intravenous ganciclovir is recommended for severe invasive disease .
I like your summary of these guidelines. Typing the whole sentences as the last paragraph amounts to shouting.
I like your reflection of current practice in your hospital.
SUMMARY OF THE PROTOCOL
Principle
Methods of prophylaxis
Threshold for treatment
Treatment options
All the above treatment should be renal dosed and reference to always be made to the renal drug handbook and pharmacist with renal knowledge.
Reflect on my practice
I like that your reflection of current practice in your hospital and a mention of limitations that include no ganciclovir being available in Nigeria.
I wish you could type references to support your arguments.
1- Serological status of the donor and recipient and the degree of immunosuppression are important risk factors of CMV disease.
2- D+/R- still at high risk even if complete their CMV prophylaxis treatment
3- Valganciclovir used as a prophylactic treatment by a dose 900 mg OD and can be adjusted according to renal function and used for 200 days in D+/R- and for 100 days in D-/R+ or D+/R+ and used for 200 days if received ATG or Alemtuzumab, but should not be given in D-/R-.
4- CMV IgG should be checked in D+/R- at 200 days, and PCR should be done after finishing prophylaxis then scheduled at two, 4,8,12 weeks.
5- Treatment should be started: in all cases of suspected tissue invasive CMV disease regardless the viral load by IV ganciclovir, and also in the cases of viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
6- Consider wise reduction of immunosuppressive medications
7- Treatment options: provided renal dose adjustment
a- Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first.
b- IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
c-IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative
in my practice we used valganciclovir (valcyte) in prophylaxis in high risk patient D+/R- or D+/R+ or when using ATG as induction or in the treatment of ACR for 3-6 months.
and we used iv ganciclovir in treating suspected tissue invasive CMV disease
of course renal dose adjustment is needed and requested
I like that your reflection of current practice in your hospital. I wish you could type references to support your arguments.
Threshold for CMV treatment:
Treatment:
In my practice VGC used as prophylaxis for 3-6 months in D+/R+ & D+/R-.
Treatment of CMV disease with VGC 900mg bd then od until negative result of CMV PCR.
I like your reflection of current practice in your hospital.
In Brazil, we do not have oral Valganciclovir, but we do have oral Ganciclovir.
D+/R-
Oral ganciclovir for six months starting fifteen days after transplantation
D+/R+
rATG 3mg/kg + CNI + mTor – monitor symptoms only
rATG 3mg/kg + CNI + MMF – oral ganciclovir for three months starting fifteen days after the transplant
rATG 6mg/kg + CNI + MMF – oral ganciclovir for six months starting fifteen days after the transplant
HIV positive – oral ganciclovir for three months starting fifteen days after transplantation
D-/R-
Just monitor symptoms. CMV PCR assay every two weeks for three to six months.
If PCR is greater than 2000, initiate intravenous Ganciclovir for at least 14 days and only suspend treatment when PCR is negative.
Dose for oral Ganciclovir prophylaxis – 250mg / 1000mg tablet three times a day
Correct the dose for renal function.
I like that your reflection of current practice in your hospital and a mention of limitations that include no oral ganciclovir being available in Brazil.
I wish you could type references to support your arguments.
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation.
1-Please summarise this protocol;
-The serological status of the donor and recipient determines the risk of disease.
-The intensity of immunosuppression determines the risk of disease.
Prophylaxis;
-D+/R- 200 days of valganciclovir.
-D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab.
-D-/R- No valganciclovir.
-The full prophylaxis dose is 900mg od.
-The dose reduction for renal impairment is commonly needed (adjusted the dose according eGFR).
Thresholds for treatment;
-Routine surveillance for viraemia is not required during prophylaxis
-CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Patients that develop viraemia or disease whilst not on prophylaxis;
-Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
-Consider appropriate reduction in immunosuppression in R+ patients with a viral load of fewer than 3 logs 10.
-Consider treatment with valganciclovir when the viral load exceeds 3 logs 10 if symptomatic or rapidly rising titre in high-risk patients.
Patients that develop viraemia or disease whilst on prophylaxis;
Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing.
Treatment;
-Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
-IV ganciclovir is indicated where enteric absorption is likely to be compromised (proven GI involvement, diarrhoea or vomiting).
-IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis)
1-Oral valganciclovir 900mg bd (for 21 days), then 900mg od (for 28 days) or until 2 x PCR negative, whichever occurs first.
2-IV ganciclovir 5mg/kg bd (for 5 days) followed by oral valganciclovir 900mg od until 2 x PCR negative.
3-IV ganciclovir 5mg/kg bd (for 14-21 days, stop date determined by 2 x PCR negative.
2-Please reflect on your practice;
-In our practice, almost the same protocol is applied;
-Prophylaxis offered for D+/R+ & D+/R- with valganciclovir for 3-6 months according
The serological status of the donor and recipient & The intensity of immunosuppression (including Induction & Maintenance therapy.
-Treatment (with advice of ID guided by Clinical pharmacist) ,we follow nearly the same protocol;
(Oral valganciclovir 900mg bd for 21 for 3/weeks, then 900mg od for 4/weeks or until 2 x PCR negative), or (IV ganciclovir 5mg/kg bd for 2/weeks , stop date determined by 2 x PCR negative).
I like that your reflection of current practice in your hospital that you use similar protocol.
Prevention of CMV disease
Surveillance
Indications of treatment with antiviral agent
Otherwise reduction of immunosuppression alone is enough
Medications used for treatment of CMV infection
1- Oral valgancyclovir
2- IV gancyclovir
Protocol
In my practice
I like your summary of these guidelines.
I like that your reflection of current practice in your hospital.
Summary
Principles:
Prophylaxis protocols
D+/R- valganciclovir for 200 days
D+/R+ OR D-/R+ valganciclovir 100 days
D-/R- no need for prophylaxis
CMV viremia
No need for routine surveillance during prophylaxis
D+/R- should have CMV IgG and CMV PCR done on blood after prophylaxis then 2,4,8,12 weeks
Treatment
Treat any suspected case of tissue invasive disease regardless of viral load.
Reduce immunosuppression in recipient+ with fewer than 3 log viral load.
Start valganciclovir in symptomatic recipient with more than 3 log viral load or rapidly rising titers.
IV ganciclovir indicated when there is tissue invasive disease or oral absorption is compromised.
PO valganciclovir 900mg bd for 21 days then 900mg od for 28days or until 2 PCR are negative.
IV ganciclovir 5mg/kg bd for 5 days then PO valganciclovir 900mg od until 2 PCR negative.
IV ganciclovir 5mg/kg bd for 14-21 days.
Ganciclovir and valganciclovir should be renal dosed.
My practise
We are in a resource limited setting so we don’t routinely do prophylaxis.
Also there are fewer cases of D+/R-.
We treat preemptively based on the symptoms and viral load.
We usually give valganciclovir 900mg bd for 21 days then 900mg od for 28days.
Routine monitoring of viremia not done.
Histology for tissue invasive disease also not routinely done due to financial constraints.
I like your summary of these guidelines.
I like that your reflection of current practice in your hospital. I must make comment on histology. Often histology is not really needed.
Okay thankyou prof noted on the histology.
Thank you prof noted on the histology
Threshold for treatment:
Treatment:
In my practice CMV prophylaxis offered for D+/R+ & D+/R- with valganciclovir for 3-6 months. Treatment of CMV disease with valganciclovir 900mg bd then 900mg od until CMV PCR is undetected.
I like your summary of these guidelines.
I like that your reflection of current practice in your hospital.
CMV status & prophylaxis :
Surveillance and testing:
Threshold for treatment:
A.CMV viraemia or disease in absence of prophylaxis:
B.CMV viraemia or disease in the presence of prophylaxis:
Treatment: Drug doses are modified according to the renal function
My practice:
I like your summary of these guidelines.
I like that your reflection of current practice in your hospital.
Most welcome prof
Main ideas
-Detecting the virological status of the donor and the recipient is mandatory to assess the CMV infection risk
-Immunosuppression burden affects the risk
-Valganciclovir can be used for prophylaxis and treatment
-D+R- high risk patients are liable to develop CMV viraemia and disease after finishing the prophylactic course.
Prophylaxis
200 days of valganciclovir for D+/R- .
100 days of valganciclovir and 200 days after ATG or Alemtuzumab for D-/R+ and D+/R+
Valganciclovir is not indicated for D-/R-
Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time after 100 days
Dose adjustment is needed for cases with renal impairment
Suspected CMV viraemia or disease must be screened
During prophylaxis ,viremia surveillance is not a must
CMV IgG need to be checked at 200 days for D+/R- cases as well as checking CMV PCR once prophylaxis has ended as the latter test in blood is the standard test.
Treatment threshold
Cases that have viremia or disease without being on prophylaxis
· All cases with suspected tissue-invasive CMV disease must receive treatment regardless of viral load
· For R+ cases with a viral load less than 3 logs 10 ,immunosuppression need to be decreased
· If viral load is more than 3 logs 10 in symptomatic or rapidly rising titre in high-risk patients ,valganciclovir will be needed
· Valganciclovir or IV ganciclovir is crucial if viral load is more than 4 logs10.
· If enteric absorption is impaired, or severe organ involvement is detected , IV ganciclovir will be indicated
Cases that have viremia or disease whilst on prophylaxis
Those cases have to be comanaged with consultant virology
Treatment
Oral versus IV therapy is chosen according to the same criteria as prophylaxis.
3 choices
-Oral valganciclovir 900mg bid for 21 days, then od for 28 days or till PCR negative twice
-IV ganciclovir 5mg/kg bd for 5 days then oral valganciclovir 900mg od until PCR
negative twice .
-IV ganciclovir 5mg/kg bd for 14-21 days, ends when PCR is negative twice
Both valganciclovir and ganciclovir need renal dose adjustment in cases with renal impairment
In our practice ,the same protocol is applied
What is your detailed summary of Sheffield Protocol?
I like reflection of your own practice.
For screening
During prophylaxis ,viremia surveillance is not a must
CMV IgG need to be checked at 200 days for D+/R- cases as well as checking CMV PCR once prophylaxis has ended as the latter test in blood is the standard test.
For prophylaxis
in D+/R- 200 days of valganciclovir .
in D-/R+ and D+/R+ 100 days of valganciclovir and 200 days after ATG or Alemtuzumab
in D-/R- Valganciclovir is not indicated
for treatment (3 options)
-Oral valganciclovir 900mg bid for 21 days, then od for 28 days or till PCR negative twice
-IV ganciclovir 5mg/kg bd for 5 days then oral valganciclovir 900mg od until PCR
negative twice .
-IV ganciclovir 5mg/kg bd for 14-21 days, ends when PCR is negative twice
Prophylaxis:
1. D+/R- 200 days of valganciclovir.
2. D-/R+ and D+/R+ 100 days of valganciclovir, 200 days after ATG or Alemtuzumab
3. D-/R- No valganciclovir
4. Prophylaxis should also be considered for any patient receiving intensified immunosuppression at any time point beyond 100 days – Consultant decision.
5. The full prophylaxis dose is 900mg od but consider modification of dose according to renal function.
Surveillance and testing by indication in suspected CMV viraemia or disease
1. Routine surveillance for viraemia is not required during prophylaxis
2. D+/R- patients should have their serostatus (CMV IgG) checked at or around 200 days
3. D+/R- patients should start surveillance with CMV PCR once they finish prophylaxis.
4. CMV PCR on blood is the standard test for all transplant patients where CMV viraemia or disease is suspected or a possibility in outpatients or inpatients, irrespective of whether on prophylaxis or not.
Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
1. Treatment is mandatory in all cases of suspected tissue-invasive CMV disease, irrespective of viral load.
2. Reduce immunosuppression in R+ patients with a viral load of < 3000
3. Consider treatment with valganciclovir when the viral load> 3000 if symptomatic or rapidly rising titre in high-risk patients.
4. Treatment with valganciclovir or IV ganciclovir is mandatory when the viral load exceeds 4 logs 10.
5. IV ganciclovir is indicated where enteric absorption is likely to be compromised.
6. IV ganciclovir is indicated in any patient with severe organ involvement (e.g. pneumonitis, encephalitis).
B. Patients that develop viraemia or disease whilst on prophylaxis
1. Discuss all such cases with a consultant virologist to agree best treatment regime and discuss resistance testing
Treatment The choice of oral versus IV therapy is determined by the abovementioned thresholds and criteria. There are three options: 1. Oral valganciclovir 900mg bd* for 21 days, then 900mg od* for 28 days or until 2 x PCR negative, whichever occurs first (off-label drug use).
2. IV ganciclovir 5mg/kg bd* for 5 days followed by oral valganciclovir 900mg od* until 2 x PCR negative.
3. IV ganciclovir 5mg/kg bd* for 14-21 days, stop date determined by 2 x PCR negative.
Consider dose reductions for renal impairment.
Our practice:
Our population is almost all D+/R+ hence we are giving prophylaxis with valganciclovir for all, for 3m.
we do modify the dose according to renal function.
For treatment, we give valganciclovir for 2-3 weeks and monitor PCR till 2 results are negative, then stop.
I like your summary of Sheffield Protocol.
I like reflection of your own practice.
III.Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation.====================================================================
Please summarise this protocol
Protocol for prophylaxis, surveillance, and treatment of CMV after renal transplantation
Principles
Prophylaxis
Surveillance and testing by indication in suspected CMV viraemia or disease
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Thresholds for treatment
A. Patients that develop viraemia or disease whilst not on prophylaxis
B. Patients that develop viraemia or disease whilst on prophylaxis
Three choices are available:-
Virological, pharmacy and other specialist advice should be sought in less straightforward cases; additional treatment may be appropriate.
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Please reflect on your practice
NICE and important information
We enhance our skills for the benefit of patients.
What is your analysis regarding the level of evidence, limitations and strengths of Sheffield Protocol?
I like your attempt at reflection of your own practice, but it is very fuzzy. I am not sure what your current practice is
Many thanks for you noted Prof.Sharma
What is your analysis regarding the level of evidence, limitations and strengths of Sheffield Protocol?
Guidelines level of evidnece I.