Treosulfan-Based Conditioning Ameliorates the Impact of Pretransplantation Measurable Residual Disease-Positivity in Acute Myeloid Leukemia Patients Allografted in Remission

Based on the MC-FludT.14/L phase III trial, treosulfan-based conditioning has become an established regimen in allogeneic hematopoietic stem cell transplantation (allo-HCT) for older or comorbid acute myeloid leukemia (AML) patients, owing to its reduced toxicity and sufficient antileukemic efficacy. In this real-world (RW) analysis, we aimed to validate these findings and assess the prognostic impact of several patient-, disease- and transplantation-related parameters, especially measurable residual disease (MRD) positivity prior to transplantation, on post-transplant outcome after treosulfan-based conditioning. We conducted a retrospective analysis of 102 patients who received conditioning with 10 g/m² treosulfan and fludarabine (Flu/Treo10) in first or second complete remission (CR) with available pretransplantation MRD status. In our RW Flu/Treo10 cohort, 3-year overall survival and relapse-free survival, cumulative incidence of relapse, and nonrelapse mortality were 68%, 53%, 38%, and 8%, respectively, comparable to the results of the MC-FludT.14/L randomized controlled trial. In contrast to common expectations, MRD positivity was not associated with adverse outcome, but we could identify the presence of secondary AML and/or a complex karyotype at diagnosis as adverse prognostic predictors for post-transplantation outcome and confirmed these findings in a validation cohort. Our analysis revealed that treosulfan-based conditioning enables reliable safety and efficacy in a RW cohort of elderly and/or comorbid AML patients who underwent allo-HCT in CR. Furthermore, our analysis implies that disease-related risk features present at diagnosis may outweigh the impact of pretransplantation MRD status on post-transplantation outcomes after treosulfan-based conditioning.