A phase I/II study of multiple-dose intravenous busulfan as myeloablation prior to stem cell transplantation

Busulfan has been previously only available in an oral formulation due to i ts poor water solubility. We report the results of a phase I study of multi ple escalating doses of intravenous busulfan (Spartaject Busulfan, Orphan E urope, Paris, France) for myeloablation prior to stem cell transplantation (SCT) in 12 patients with chronic myeloid leukemia, acute myeloid leukemia or acute lymphocytic leukemia. One patient received allogeneic SCT; the oth er 11 patients received autologous SCT. The first six patients received i.v . busulfan diluted in 50 ml of 0.9% normal saline and the last six patients received busulfan in a 500-ml 5% dextrose solution. All patients experienc ed profound myelosuppression and all but one demonstrated hematopoietic eng raftment Toxicity was mild or moderate and there were no toxic deaths attri butable to busulfan. Of note, there were no cases of veno-occlusive disease of the liver. Busulfan plasma concentrations were determined by gas chroma tography with electron capture detection and showed little intrapatient var iability. In most cases there was no significant difference between the fir st and last dose PK parameters. These data suggest that dose adjustment bas ed on first dose PK data could allow uniformity of busulfan dosing for pati ents receiving SCT.