Abstract

Hepatic veno-occlusive disease is a major limiting factor of high-dose chemotherapy in children. The cells lining the hepatic vascular endothelium express blood group A and/or B antigens according to the patient's blood group. We designed a study evaluating the impact of platelet concentrates containing ABO-incompatible plasma transfused to young children with a high risk of hepatic veno-occlusive disease. In all, 186 consecutive children (median age: 4 years, range: 0.75-17 years), treated with high-dose chemotherapy containing busulfan followed by hematopoietic stem cell transplantation for neuroblastoma (n=112) or brain tumor (n=74) between 1988 and 1998, were investigated. The main endpoint was the occurrence of hepatic veno-occlusive disease. Multivariate analysis was performed using a Cox's regression model with transfusion of platelet concentrates containing ABO-incompatible plasma as a time-dependent covariate. We found that 73 out of 186 (39%) children developed hepatic veno-occlusive disease after transplantation. Multivariate analysis demonstrated that two factors significantly increased the risk of hepatic veno-occlusive disease occurrence: transfusion of platelet concentrates containing ABO-incompatible plasma (P=0.003) and use of melphalan in the conditioning regimen (P=0.006). Conversely, the number of platelet concentrates transfusions per week, child's age, weight, sex, and use of cyclophosphamide in the conditioning regimen had no effect. Transfusion of platelet concentrates containing ABO-incompatible plasma increases the risk of hepatic veno-occlusive disease in young children treated with a busulfan-containing regimen. Binding of A and/or B antigens expressed on the surface of hepatic endothelial cells may promote this complication. Transfusion of platelet concentrates containing ABO-incompatible plasma should be avoided in these children.

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