Fludarabine/TBI 8 Gy versus fludarabine/treosulfan conditioning in patients with AML in first complete remission: A Study from the Acute Leukemia Working Party of the EBMT

Abstract: The optimal reduced intensity conditioning (RIC) regimen is a matter of debate. We retrospectively compared conditioning with fludarabine plus fractionated total body irradiation of 8 Gy (FluTBI) and fludarabine plus treosulfan 30, 36 or 42 g/m² (FluTreo) in 754 patients with AML above the age of 40 years undergoing an allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission (CR). In a multivariate analysis, FluTBI was associated with a significantly lower probability of relapse than FluTreo (hazard ratio (HR) 0.59 [95% CI, 0.38–0.93], p = 0.023). There was no significant difference in leukemia-free survival (LFS), overall survival (OS), graft-versus-host disease-free and relapse-free survival (GRFS), or acute and chronic graft-versus-host disease (GVHD). After balancing patient characteristics by propensity score matching of 115 patients in each group, FluTBI retained its significantly lower probability of relapse compared to FluTreo (18.3% vs. 34.7%, p = 0.018) which was counteracted by a higher non-relapse mortality (16.8 vs. 5.3%, p = 0.02). Thus, OS and GRFS at 2 years were similar between groups (OS 66.9% vs. 67.8%, GRFS 50.3% vs. 45.6%). We conclude that both conditioning regimens are effective and safe, but FluTBI may better be reserved for younger patients below the age of 55 years.