GVHD and GRFS in patients with acute myeloid leukemia undergoing allogeneic HCT with treosulfan- versus reduced-intensity busulfan-based conditioning: a subgroup analysis of a randomized phase 3 trial

Abstract

Acute myeloid leukemia (AML) is the most common indication for allogeneic hematopoietic cell transplantation (alloHCT), yet graft-versus-host disease (GVHD) remains a major post-transplant complication. Conditioning regimens, particularly reduced-intensity approaches, are critical in optimizing outcomes. This subgroup analysis of the phase 3 MC-FludT.14/L trial compared treosulfan-fludarabine with reduced-intensity busulfan-fludarabine in 352 AML patients (aged 31–70) undergoing alloHCT. The primary endpoint was 24-month event-free survival (EFS); secondary endpoints included overall survival (OS), GVHD incidence, relapse/progression, and non-relapse mortality (NRM). Treosulfan compared to busulfan demonstrated superiority: 24-month EFS was 65% vs. 53% (p = 0.01), and OS was 73% vs. 65%. EFS benefits were consistent across AML risk categories and notably higher in patients with hematopoietic cell transplantation comorbidity index >2 (62% vs. 42%, p = 0.02). Treosulfan also showed lower NRM and relapse rates. GVHD outcomes favored treosulfan, with a significantly lower incidence of extensive chronic GVHD at 24 months (15.1% vs. 28.1%, p = 0.01). GVHD-free and relapse-free survival was also improved (53% vs. 40%, p = 0.02). The safety profile was more favorable with treosulfan. These findings support treosulfan-fludarabine as a more effective and safer conditioning regimen than busulfan-fludarabine for AML patients undergoing alloHCT, particularly those at higher risk.