Optimizing Outcomes in Mismatched Unrelated Donor Allogeneic Transplantation: Post-Transplant Cyclophosphamide's Dual Impact on Graft versus Host Disease Incidence and Overall Survival: Retrospective Analysis on Behalf of Polish Adult Leukemia Group.

Allogeneic hematopoietic cell transplantation (allo-HSCT) stands as an effective treatment method for various hematologic malignancies. However, graft-versus-host disease (GvHD), an intricate immunological phenomenon where donor immune cells target recipient tissues, remains a significant challenge, particularly in mismatched unrelated donors (MMUD). Post-transplant cyclophosphamide (PTCy) has emerged as a promising immunosuppressive strategy, revolutionizing haploidentical transplantation and demonstrating promise in MMUD settings. : This study aimed to evaluate the impact of PTCy on MMUD allo-HSCT outcomes, specifically its effects on GvHD incidence and overall survival, compared to anthitymocyte globulin (ATG). : One hundred seventy-four patients were classified into three groups based on the type of transplantation: PTCy-haplo (114/174; 65.5%), PTCy-MMUD (23/174; 13.2%), and ATG-MMUD (37/174; 21.2%). : Our findings showed that PTCy-MMUD significantly reduced acute GvHD occurrence compared to PTCy-haplo and ATG-MMUD approaches ( = 0.006). The delayed onset of acute GvHD in the PTCy-MMUD group suggests a more controlled immune reconstitution, contributing to the lower incidence. Importantly, PTCy-MMUD exhibited enhanced five-year overall survival rates, aligning with the notion that reduced GvHD correlates with improved patient outcomes ( = 0.032). : We believe that this study contributes valuable insights into PTCy-MMUD's management, underscoring its potential to significantly reduce GvHD incidence and enhance survival outcomes. Although further investigations and clinical trials are warranted, this research underscores the promising role of PTCy-based GvHD prophylaxis in improving MMUD allo-HCT success.