Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Sep 2004
Clinical TrialDose modification protocol using intravenous busulfan (Busulfex) and cyclophosphamide followed by autologous or allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies.
We evaluated the safety and toxicity through a 5-cohort dose-modification model of once-daily administration of IV busulfan (Bu) in combination with high-dose cyclophosphamide (Cy) as preparative therapy for stem cell transplantation. Twenty-one adult patients with hematologic malignancies were evaluated. Eleven patients underwent autologous and 10 patients underwent HLA-matched sibling allogeneic transplantation. ⋯ Interpatient variability in AUCs was observed in patients within and between cohorts, but no statistically significant interpatient differences were observed in Bu half-life, volume of distribution, clearance, or dose-adjusted area under the curve. Further, minimal variability in Bu pharmacokinetics was observed between the 2 evaluations performed in each patient, thus reflecting the stability of Bu disposition within individual patients. On the basis of the dosing guidelines and schedule outlined in this study, our data suggest that administration of IV Bu 3.2 mg/kg IV every 24 hours for 4 doses in combination with Cy may result in excessive toxicity.