Hepatic dysfunction following busulfan and cyclophosphamide myeloablation: a retrospective, multicenter analysis.
Veno-occlusive disease continues to be a significant cause of morbidity and early mortality following bone marrow transplantation. This study retrospectively analyzes the incidence and risk factors for severe VOD in 350 patients treated with 4 days of busulfan (total 16 mg/kg) and 2 days of cyclophosphamide (120 mg/kg) at four marrow transplant centers. Using the criteria defined by McDonald et al (Hepatology 1984; 4: 116-122), 93/350 (27%) developed VOD (11% mild, 5% moderate and 11% severe). Multivariate analysis revealed the following risk factors to be significantly associated with severe VOD: pretransplant transaminase and alkaline phosphatase elevation, ciprofloxacin antibiotic prophylaxis, use of estrogen/progestins or vancomycin during the peritransplant period and methotrexate for GVHD prophylaxis. Mild to moderate grades of VOD were not associated with significantly increased mortality but mortality was higher in patients with severe VOD (31%, P = 0.0013). These data suggest that risk factors for VOD may depend on the preparative regimen used and suggest that use of these risk factors may identify a subgroup of patients that can be targetted for studies of prevention of VOD.
Styler
M J
MJ
Department of Neoplastic Diseases, Hahnemann University Hospital, Philadelphia, PA 19102, USA.
Crilley
P
P
Biggs
J
J
Moul
J
J
Copelan
E
E
Topolsky
D
D
Avalos
B
B
Penza
S
S
Sabol
P
P
Downs
K
K
Szer
J
J
Brodsky
I
I
Marks
D I
DI
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects; D005260:Female; D030342:Genetic Diseases, Inborn / Q000628:therapy; D006086:Graft vs Host Disease / Q000517:prevention & control; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D015994:Incidence; D015993:Life Tables; D008107:Liver Diseases / Q000150:complications; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000139:chemically induced; D015999:Multivariate Analysis; D009369:Neoplasms / Q000628:therapy; D011372:Progestins / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014640:Vancomycin / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D004967:Estrogens; D007166:Immunosuppressive Agents; D011372:Progestins; D002939:Ciprofloxacin; D014640:Vancomycin; D003520:Cyclophosphamide; D002066:Busulfan; D008727:Methotrexate