IV Busulfan-Based Reduced Intensity Regimen (RIC) Before Allogeneic Stem Cell Transplantation Is Well Tolerate And Effective In Patients With Hematological Diseases

Busulfan-based RIC has been widely used in Allogeneic setting, showing good safety profile and efficacy. The intravenous formulation, Busilvex, is considered a step forward as compared to oral form because of reproducible biodisponibility and pharmacokinetic. In this study, we evaluated the toxic profile and clinical efficacy of a busilvex-based RIC. Since 2005, 78 patients received a uniform RIC consisting of busilvex 3.2 mg/kg/day for 2 days, Fludarabine 40 mg/m2/days for 5 days, and thymoglobulin 2.5 mg/kg/day for 2 days. Cyclosporine was used as post-graft immunesuppression. The median age was 58 years (24-70), and 41% of patients suffered from acute myeloid leukemia. 81% were in complete or partial remission before RIC. Donor was a HLA identical sibling for 64% of patients. 43% of patients received previous high dose chemotherapy. The median follow-up was 16 (2-51). No patients developed venocclusive disease (VOD). The cumulative incidence (CI) for grade II-IV acute graft versus host disease (GVHD) was 31%, and for extensive chronic GVHD was 25%. Overall 9 pts died from TRM for a 2 year CI of 16% (8-28). In addition, 18 pts relapsed or progressed for a 2 year CI of relapse progression of 30% (17-48). Overall the 2-y overall survival (OS) and disease free survival (DFS) probabilities were respectively 71% (56-82) and 58% (42-72). This retrospective study shows that busilvex-based RIC is well tolerate with low TRM incidence in a high-risk cohort of patients. Particularly, the extensive chronic GVHD incidence was low probably due to thymoglobulin use for HLA identical donors. VOD was absent even if reversible hepatic toxicity was frequently observed. These promising safety results invited us to assess the impact of higher dose of IV Busulfan in an ongoing trial in order to improve disease control.