Tereza Coman, Stéphane Morisset, Raynier Devillier, Maud D'Aveni, Frederic Baron, Jacques Olivier Bay, Jean El-Cheikh, Karine Bilger, Claude-Eric Bulabois, Cristina Castilla-Llorente, Patrice Ceballos, Yves Chalandon, Sylvain Chantepie, Magalie Joris, Patrice Chevallier, Mustafa Alani, Jerôme Cornillon, Etienne Daguindeau, Edouard Forcade, Chama Mokeddem, Gaelle Guillerm, Hélène Labussiere, Philippe Lewalle, Mikael Loschi, Johan Maertens, Florent Malard, Jean-Valère Malfuson, Natacha Maillard, Jean Baptiste Mear, Stéphanie Nguyen-Quoc, Cécile Pivert, Xavier Poire, Marie-Thérèse Rubio, Felipe Suarez, Pascal Turlure, Alban Villate, Ibrahim Yakoub-Agha, Nicole Raus, Marie Robin, Anne Huynh, Mauricette Michallet
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.