Intravenous busulfan: in the conditioning treatment of pediatric patients prior to hematopoietic stem cell transplantation.

An intravenous formulation of busulfan, a cytotoxic bifunctional alkylating agent, has been developed to replace oral busulfan as a conditioning treatment prior to hematopoietic stem cell transplantation (HSCT) in pediatric patients. Doses of intravenous busulfan based on actual bodyweight, but not age, reduce inter- and intraindividual variability in exposure. In a study of intravenous busulfan as a conditioning treatment prior to allogeneic or autologous HSCT, the majority of pediatric patients, who received one of five bodyweight-based doses, achieved busulfan area under the plasma concentration-time curve (AUC) values within the targeted therapeutic range. Although mean busulfan clearance values were highly variable between bodyweight strata, exposure was not affected, with no significant differences between bodyweight groups in mean AUC values. The achievement of therapeutic AUC values with intravenous busulfan resulted in a high rate of sustained engraftment, low transplant-related mortality, and promising survival outcomes post-transplant. Intravenous busulfan was considered to be well tolerated, in the particular context of HSCT, and no failure of HSCT due to organ toxicity was reported. Nonhematologic adverse events commonly associated with busulfan conditioning regimens were frequent, but generally of mild to moderate severity. The intravenous busulfan regimen was frequently associated with elevated liver enzymes, but hepatic veno-occlusive disease (HVOD) was infrequent, of mild to moderate severity, and resolved within 10 days of diagnosis. Unlike oral busulfan, intravenous busulfan does not appear to be associated with severe HVOD or death due to organ toxicity.