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.
Desai et al. (2026) studied this question.