Valganciclovir-induced leukopenia in liver transplant recipients: influence of concomitant use of mycophenolate mofetil.
BACKGROUND
An increased incidence and magnitude of leukopenia during concomitant treatment with valganciclovir (VGC) and mycophenolate mofetil (MMF) has been reported.


OBJECTIVE
To evalute the incidence and severity of leukopenia and neutropenia among liver recipients treated with VGC and related factors.


METHODS
Retrospective analysis of clinical and analytical data related to leukopenia (<3000 leukocytes/mm(3)) and neutropenia (<900 neutrophils/mm(3)) in liver transplant patients who were treated with VGC from 2003 to 2007. We examined the influence of concomitant administration of MMF and development of subsequent infections.


RESULTS
Among 209 liver transplants, 40 treatments with VGC were prescribed in 37 patients (17.7%), 12 of which (30%) were associated with MMF. The patients has an average age of 49.7 +/- 12.7, body mass index (BMI) of 27.28 +/- 5.17, and Model for End-stage Liver Disease Score (MELD) 12.45 +/- 7.5. The daily average dose of VGC was 1440 +/- 446.5 mg and MMF, 1454.5 +/- 350.3 mg. We observed a decrease of 30% in initial leukocyte count (5353.7 +/- 2706.6) and 40% in neutrophil count (3600 +/- 2182.1). With no relationship to total dose or BMI-adjusted dose of VGC nor concomitant administration of MMF. The initial leukocyte count was significantly lower (4411 +/- 1930 vs 6206 +/- 3053; P = .03) and underwent a main drop (2344.7 +/- 1974.3 vs 898.1 +/- 2435.6; P = .04) when leukopenia developed. In the induced neutropenia group, previous leukocyte count (3797.1 +/- 1223.9 vs 5683.9 +/- 2829.3; P = .01), MELD (18.7 +/- 8.8 vs 11.1 +/- 6.6; P = .01), and the creatinine pretreatment (1.44 +/- 0.4 vs 1.09 +/- 0.3; P = .01) were significantly different. Subsequent infections induced by the leukopenia were not observed.


CONCLUSIONS
In our series, the concomitant use of VGC and MMF was not associated with a greater incidence of leukopenia and/or neutropenia than VGC administration alone. Previous leukocyte count was associated with them. MELD and renal dysfunction are factors related to severe neutropenia. Leukopenia was not associated with a greater incidence of infections.
Molina Perez
E
E
Abdominal Transplantation Unit, Universitary Hospital Complex of Santiago de Compostela, Spain. esther.molina.perez@sergas
Fernández Castroagudín
J
J
Seijo Ríos
S
S
Mera Calviño
J
J
Tomé Martínez de Rituerto
S
S
Otero Antón
E
E
Bustamante Montalvo
M
M
Varo Perez
E
E
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D015992:Body Mass Index; D003404:Creatinine / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects / Q000031:analogs & derivatives*; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D015994:Incidence; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced* / Q000453:epidemiology; D017093:Liver Failure / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D000077562:Valganciclovir
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D003404:Creatinine; D000077562:Valganciclovir; D009173:Mycophenolic Acid; D015774:Ganciclovir