Leukopenia complicates cytomegalovirus prevention after renal transplantation with alemtuzumab induction.
BACKGROUND
Cytomegalovirus (CMV) is a major cause of morbidity after transplantation. Valganciclovir (VGCV) is commonly utilized for CMV prophylaxis but can cause leukopenia, with risk compounded by the use of myelosuppressive immunosuppression. By utilizing a preemptive therapeutic strategy with VGCV targeted only toward patients at risk for developing CMV disease, the rate and extent of leukopenia may be reduced.


METHODS
VGCV prophylactic and preemptive strategies were compared in renal transplant recipients receiving alemtuzumab induction and prednisone-free maintenance with tacrolimus and mycophenolate mofetil (MMF). Patients were risk-stratified by CMV serologic status. All donor seropositive/recipient seronegative (D+/R-) patients, February 2002-January 2004 (n=32), received prophylaxis with VGCV 450 mg daily for 3 months. Outcomes of D+/-/R+ patients were compared. Patients in the first cohort, February 2002-October 2002 (n=61), received prophylaxis as described. In the second cohort, October 2002-January 2004 (n=110), patients were monitored by quantitative CMV-polymerase chain reaction (PCR) every 2 weeks for 3 months. If the CMV load was above laboratory threshold, VGCV 450 mg daily was initiated for 1 month or until viremia cleared.


RESULTS
Comparing preemptive therapy versus prophylaxis in D+/-/R+ patients, there was a lower incidence of leukopenia (67% vs. 82%, P=0.039) and trend toward less granulocyte-colony stimulating factor (G-CSF) use (24% vs. 33%, P=0.196), but higher CMV disease rate (15% vs. 3%, P=0.02). One limitation was strategy compliance: 41% (7 of 17) of preemptive patients who developed CMV missed at least 1 CMV-PCR before diagnosis. One-year patient (98.2% vs. 98.4%) and death-censored graft (100% vs. 98.4%) survival was similar.


CONCLUSIONS
Antiviral toxicity may be decreased with preemptive therapy, but effectiveness for CMV prevention seems dependent upon monitoring compliance.
Walker
Jennifer K
JK
1 Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL 60611, USA. jwalker@nmh.org
Scholz
Lisa M
LM
Scheetz
Marc H
MH
Gallon
Lorenzo G
LG
Kaufman
Dixon B
DB
Rachwalski
Erik J
EJ
Abecassis
Michael M
MM
Leventhal
Joseph R
JR
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D007970:Leukopenia / Q000453:epidemiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011183:Postoperative Complications; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab