Management of CMV after transplantation

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Pre-transplant:
All the donors and recipients of kidney transplants (both
living and deceased) should be tested for status of CMV by CMV IgG in the blood. If
there is history of recent transfusion, pre-transfusion status should be
regarded as the true status of CMV. The status of both donor and recipient for a given
pair. should be documented in the record post-transplant
Post-transplant:
Prophylaxis:
  • CMV related illness is common in the KTRs and the risk is
    highest in D+/R- group and the least in D-/R-. 
  • We do prophylaxis KTRs with Valganciclovir (Valcyte) 900 mg
    daily (adjusted for renal function) for 6 months in D+/R- group, and 450
    mg daily for 3 months for R+ group regardless of the donor status. No CMV
    prophylaxis is required for the D-/R- group (this group
    receives acyclovir for prophylaxis of other opportunistic viruses like HSV and
    HZV).
  • Leukopenia is a side effect of Valcyte and the anti-metabolites.
    If leukopenia is encountered, valcyte dose or dose of the anti-metabolite (eg
    MPA derivative, azathioprine, or TOR inhibitor) or both be adjusted based on
    the physician’s discretion (consider checking for CMV pcr). Consider use of
    G-CSF if the absolute neutrophil count is less than 500. If Valcyte dose must reduced or discontinued for
    more than one week, weekly monitoring of CMV Quantitative (blood PCR) could be
    considered for a total of 3-4 months from the time of transplant.
  • Routine CMV PCR testing is NOT recommended in patients
    receiving full doses of prophylactic therapy unless there is some other
    clinical suspicion for breakthrough CMV infection.

Treatment – CMV related illness is divided into:

1. CMV infection:
Active viral replication (based on blood PCR) without any
symptoms attributable to CMV. It is recommended to start treatment even at a
low level of viral load. It should be noted that a change of viral load less
than or greater than three times the previous value (0.5 times log 10) does not
mean a true change in the viral load. 

Valcyte at treatment dose (900 mg BID), adjusted for renal
function) is recommended for treatment. Weekly Quantitative PCR
in plasma is recommended while on treatment and duration of treatment to
continue at least for two consecutive negative Quantitative PCRs, and not less
than a total of 2 weeks. Secondary prophylaxis at the end of treatment (at
prophylaxis dose of Valcyte) for a month or two after finishing treatment can
be considered if suspicion for relapse is high.
2. CMV disease:
Active viral replication plus symptoms: Either 1) a flu-like
illness with fever and general malaise,  often associated with leukopenia or 2) tissue
invasive disease (commonly GI but also including hepatitis, pulmonary and
rarely uveitis and encephalitis).
Treatment either with Valcyte at treatment dose or IV
Ganciclovir at treatment dose (for life threatening illness and GI disease). IV
Ganciclovir can be switched to corresponding dose of Valcyte at any time during
the therapy if considered appropriate. Monitoring for response and duration of
treatment are similar to CMV infection treatment. Please note that tissue
invasive disease can rarely occur with negative quantitative PCR in blood
(especially when disease is limited to the GI tract). In that situation,
duration of therapy should consist of at least two weeks of the antiviral or
longer as guided by clinical response. Secondary prophylaxis at the end of
treatment with Valcyte for a month or two (at prophylaxis dose of valcyte) can
be considered if suspicion for relapse is high. 
Lowering of immunosuppression should be considered starting with the
anti-metabolite (definitely for life threatening illness) at the discretion of
physician. If leukopenia is encountered, it is recommended to lower
anti-metabolite rather than lowering valcyte dose to avoid failure of therapy
and resistance of CMV to valcyte.
CMV resistance, although rare, should be suspected if no
response to therapy even after a total duration of 5 weeks with Valcyte. If CMV
resistance is confirmed, consider foscarnet for treatment, the dose of which
should be also adjusted based on renal function
CrCl (ml/min)
Maintenance/Prophylaxis
Treatment
Valcyte
>60
900 mg q
day
900 mg bid
40-59
450 mg q
day
450 mg bid
25-39
450 mg q 2
days
450 mg q
day
10-24
450 mg
twice weekly
450 mg q 2
days
<10
100 mg 3
times a week, after HD
200 mg 3
times a week, after HD
IV Ganciclovir
>70
5 mg/kg q
12 hr
50-69
2.5 mg/kg q
12 hr
25-49
2.5 mg/kg q
24 hr
10-24
1.25 mg/kg
q 24 hr
<10
1.25 mg/kg
3 times a week after HD

 

Posted by Raj Sabaru

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