Can we move beyond myeloablative conditioning (MAC)? A comparison of MAC versus reduced intensity conditioning (RIC) in patients aged younger than 65 years undergoing allogeneic haematopoietic cell transplantation using ATG-PTCy-CSA for GVHD prophylaxis.

Allogeneic haematopoietic cell transplantation (HCT) offers a curative option for numerous haematological disorders; however, its myeloablative conditioning (MAC) regimens are associated with substantial toxicity. Reduced intensity conditioning (RIC) regimens were developed to mitigate transplant-related toxicity and broaden eligibility-particularly for older or medically unfit patients-though their use in younger, fit patients remains debated. In this retrospective study, we compared outcomes between MAC and RIC in patients aged younger than 65 years undergoing allogeneic HCT with a unified graft-versus-host disease (GVHD) prophylaxis regimen comprising anti-thymocyte globulin (ATG), post-transplant cyclophosphamide (PTCy) and ciclosporin (CsA). Propensity score matching was applied to reduce confounding. At 2 years post-transplant, there were no statistically significant differences in overall survival (OS) between the groups (MAC: 68.6% vs. RIC: 65.9%; p = 0.61) or in non-relapse mortality (NRM) (MAC: 15.8% vs. RIC: 12.5%; p = 0.26). However, relapse incidence was significantly higher in the RIC group (27.0%) than in the MAC group (16.1%; p = 0.01). These findings reinforce the continued relevance of MAC in younger patients who are candidates for intensive therapy, as it appears to offer superior disease control without a concomitant increase in NRM. Prospective studies are warranted to further delineate the role of conditioning intensity in the context of contemporary GVHD prophylaxis.