GVHD prophylaxis with PTCy, ATG, PTCy+ATG, or no in vivo T-cell depletion in RIC matched-donor PBSC transplantation for AML and MDS.

Post-transplant cyclophosphamide (PTCy) has transformed graft-versus-host disease (GVHD) prophylaxis but its role in matched-donor reduced-intensity allogeneic hematopoietic cell transplantation (allo-HCT) remains uncertain. We retrospectively analyzed adults with AML or MDS reported to the French-Belgian-Swiss EBMT/SFGM-TC registry who received a first allo-HCT from a matched related (MRD) or matched unrelated donor (MUD) after reduced-intensity conditioning (RIC) with peripheral blood stem cells between 2014 and 2022. Among 3624 patients, GVHD prophylaxis comprised immunosuppressive agents without in vivo T cell depletion (NONE, n = 213), PTCy±immunosuppression (PTCy, n = 97), ATG±immunosuppression (ATG, n = 3 286), or PTCy+ATG±immunosuppression (PTCy+ATG, n = 28). In multivariable competing-risk models, PTCy was associated with a significant reduction of grade III-IV aGVHD compared to ATG (HR 0.44, p = 0.026). Both PTCy and ATG were associated with a lower incidence of extensive cGVHD vs NONE, without affecting NRM or relapse risk. With a median follow up of 16.6 months, the probability of 1-year OS, PFS and GRFS were 69.92%, 62.46% and 48.39%, regardless of donor type or GVHD prophylaxis group. These large, homogeneous registry data support PTCy as an effective alternative to ATG for GVHD prophylaxis in RIC MRD/MUD allo-HCT for AML/MDS, and provide a benchmark while ongoing randomized trials mature.