Allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies after dose-escalated treosulfan/fludarabine conditioning

Abstract

Purpose: Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 × 10 g/m2 was the basis for dose escalation in this prospective, multicenter trial. Patients and Methods: Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m 2, 12 g/m2, or 14 g/m2 of intravenous treosulfan, which was administered on days -6 to -4 combined with fludarabine 30 mg/m2 on days -6 to -2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%). Results: No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/ progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568). Conclusion: Treosulfan-based conditioning was feasible at all three doses. The 3 × 14 g/m2 dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate. © 2010 by American Society of Clinical Oncology.