Improved early transplant outcomes with reduced‐dose PTCy and low‐dose ATG in matched unrelated donor allogeneic transplantation for acute myeloid leukaemia

Post-transplant cyclophosphamide (PTCy) is associated with infectious and organ toxicities. Dose optimization may reduce these risks while maintaining efficacy. We initiated a prospective pilot study in July 2024 evaluating reduced-dose PTCy (35 mg/kg on days +3 and +4; PTCy70) with low-dose anti-thymocyte globulin (ATG) (2 mg/kg) in adults with acute myeloid leukaemia (AML) undergoing matched unrelated donor (MUD) transplantation. Outcomes were compared with a contemporary cohort receiving PTCy100 with ATG 2 mg/kg. Of 173 patients, 41 received PTCy70. Platelet engraftment was faster with PTCy70, 13 vs. 16 days (p < 0.001). In multivariable analysis, PTCy70 was associated with lower risk of bloodstream infections (hazard ratio [HR] 0.39, 95% confidence interval [CI], 0.19-0.78, p = 0.007). At day+100, the incidence of grade II-IV (30.4% vs. 20.3%, p = 0.17), grade III-IV acute graft-versus-host disease (GVHD) (3% vs. 3%, p = 0.08) and non-relapse mortality (3.8% vs. 2.8%, p = 0.67) were similar between groups. Cardiac events were less frequent with PTCy70 (5% vs. 17%; p = 0.06). No cases of sinusoidal obstruction syndrome were observed in the PTCy70 group. At 12 months, relapse (11.1% vs. 15.3%, p = 0.88) and overall survival (79.6% vs. 83.2%, p = 0.87) did not differ between groups. PTCy70 was associated with faster platelet engraftment, fewer bloodstream infections and cardiac events without compromising GVHD, relapse or survival, supporting evaluation in randomized trials.