Effect of the Thiotepa Dose in the TBF Conditioning Regimen in Patients Undergoing Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Complete Remission: A Report From the EBMT Acute Leukemia Working Party

Background: Allogeneic stem cell transplantation is a potentially curative therapy for patients with acute myeloid leukemia (AML) after achieving complete remission (CR). The aim of this study is to evaluate the optimal dose of thiotepa, administered as part of the thiotepa-busulfan-fludarabine (TBF) conditioning regimen for allogeneic stem cell transplantation in adults with AML in CR. Patients and Methods: In a retrospective multicenter analysis, we identified 240 patients allotransplanted from matched related or unrelated donors or T replete haplo-identical donors. We compared the transplantation outcomes of patients who received 5 mg/kg thiotepa and 2 days of intravenous busulfan at 6.4 mg/kg (T1B2F) versus those who received 10 mg/kg thiotepa with 2 days of intravenous busulfan at 6.4 mg/kg (T2B2F). The median follow-up was 20 months. Results: On univariate analysis, the incidence of acute graft versus host disease (GVHD) grade II to IV was significantly lower in the T1B2F group (19%) versus 32% in the T2B2F group (P =.029). This result was confirmed on multivariate analysis; acute GVHD was higher for patients receiving T2B2F (hazard ratio, 2.22; P =.024). No significant change in non-relapse mortality, progression-free survival, or overall survival was observed between the 2 groups. Conclusion: T2B2F is associated with a higher incidence of acute GVHD compared with T1B2F. These results suggest that a lower dose-intensity of thiotepa and busulfan in the TBF regimen may yield better results in patients with AML in CR. We conducted a multicenter retrospective analysis of 240 patients to evaluate the optimal dose of thiotepa, administered as part of thiotepa-busulfan-fludarabine conditioning regimen for allogeneic stem cell transplantation in adults with acute myeloid leukemia in complete remission. This study suggested that a lower dose-intensity of thiotepa and busulfan (5 mg/kg thiotepa and 2 days of intravenous busulfan at 6.4 mg/kg) in the thiotepa-busulfan-fludarabine regimen may yield better outcomes.