Impact of graft‐versus‐host disease prophylaxis strategies on <scp>GvHD</scp> ‐free/relapse‐free survival in young adults undergoing unrelated donor allogeneic haematopoietic cell transplantation: A propensity score‐matched analysis

Young adults (YAs) undergoing allogeneic haematopoietic stem cell transplantation (HSCT) represent a unique population with distinct medical and psychosocial needs. Optimizing graft-versus-host disease (GvHD) prophylaxis in this population remains critical to improving outcomes. We performed a retrospective analysis of YAs undergoing unrelated donor HSCT using a contemporary Center for International Blood and Marrow Transplant Research (CIBMTR) dataset. GvHD-free, relapse-free survival (GRFS) at 24 months was evaluated across three GvHD prophylaxis strategies: Group A (post-transplant cyclophosphamide [PTCy] + calcineurin inhibitor [CNI] + mycophenolate mofetil [MMF]), Group B (CNI + methotrexate [MTX]/MMF), and Group C (CNI + MTX/MMF + anti-thymocyte globulin [ATG]). A propensity score-matched (PSM) analysis was conducted to adjust for baseline differences. A total of 1387 YA patients were included. In the total cohort, 24-month GRFS was 58.9% (confidence intervals [95% CI], 53-64) in Group A, 32.2% (95% CI, 29-36) in Group B and 44.2% (95% CI, 39-49) in Group C (p < 0.001). On multivariable analysis (MVA), both Group A (hazard ratio [HR] = 0.44; 95% CI, 0.35-0.54) and Group C (HR = 0.79; 95% CI, 0.70-0.90) showed improved GRFS compared to Group B. In the propensity score-matched cohort, GRFS at 24 months remained higher in the PTCy group (58.2%, 95% CI, 52-64) versus the CNI-MTX/MMF ± ATG group (32.9%, 95% CI, 27-39; p < 0.001), with PTCy independently associated with improved GRFS (HR = 0.48; 95% CI, 0.40-0.60; p < 0.001). PTCy-based prophylaxis also reduced non-relapse mortality (NRM), with no significant differences in relapse or overall survival (OS) between groups. In this large, retrospective analysis, PTCy was associated with significantly improved GRFS and reduced NRM in YAs undergoing unrelated donor HSCT. These findings support the use of PTCy-based regimens in this population and warrant prospective evaluation.