Work

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

Year: 2025

Type: article

Abstract: Background Based on the MC-FludT.14/L phase III trial Treosulfan-based conditioning has become an established regimen in allogeneic hematopoetic stem cell transplantation (allo-HCT) for older or comorbid acute myeloid leukemia (AML) patients due to its reduced toxicity and sufficient antileukemic efficacy. Objective In this real-world (RW) analysis, we aimed to validate these findings and assess the prognostic impact of several patient-, disease- and transplant-related parameters, especially measurable residual disease (MRD) positivity prior to transplant, on posttransplant outcome after Treosulfan-based conditioning. Study Design We conducted a retrospective analysis of 102 patients who received conditioning with 10g/m 2 Treosulfan and Fludarabin (Flu/Treo10) in 1 st / 2 nd complete remission (CR) with available pretransplant MRD status. Results In our real-world Flu/Treo10-cohort, 3-year (yr) 3-year overall (OS) and relapse-free survival (RFS), relapse incidence (CIR) and non-relapse mortality (NRM) were 68%, 53%, 38% and 8%, thus comparable to the randomized-controlled trial (RCT). In contrast to common expectations, MRD positivity was not associated with adverse outcome, but we could identify the presence of secondary AML (sAML) and/or a complex karyotype (cKT) at diagnosis as adverse prognostic predictors for posttransplant outcome and confirmed these findings in a validation cohort. Conclusion In this analysis we showed that Treosulfan-based conditioning enables reliable safety and efficacy in a RW cohort of elderly and/or comorbid AML patients allografted in CR. Furthermore, our analysis implies that disease-related risk features present at diagnosis may outweigh the impact of pretransplant MRD-status on posttransplant outcome after Treosulfan-based conditioning.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.10.011