Optimized GVHD Prevention in HLA-Mismatched Unrelated Allogeneic HCT Using a PTCY-Based Approach.

Although post-transplant cyclophosphamide (PTCY)-based prophylaxis has become a widely adopted strategy for preventing graft-versus-host disease (GVHD) in 9 out of 10 HLA-mismatched unrelated donors (MMUDs), allogeneic hematopoietic cell transplants (allo-HCTs), data on the safety and efficacy of PTCY in this setting remain limited. This single-center study investigates the outcomes of 94 adults with hematological malignancies undergoing MMUD allo-HCT with PTCY and tacrolimus (Tac) (PTCY-Tac) between 2014 and 2023. The median age was 53 years, and 60.6% were male. Peripheral blood stem cells were infused in all cases. By Day +100, the cumulative incidence of Grades II-IV and Grades III and IV acute GVHD were 33.0% and 9.7%, with 2-year incidence of moderate-to-severe chronic GVHD at 12.6%. By Day +30, 40.8% of patients experienced bacterial bloodstream infections, and 52.4% had cytomegalovirus (CMV) reactivation before letermovir prophylaxis. With letermovir's introduction, CMV reactivation rates dropped significantly, with only one case reported. At 3 years, overall survival was 60.8%, non-relapse mortality was 23%, and the cumulative incidence of relapse was 24.5%. HLA Class I or II mismatches did not affect key outcomes or GVHD rates. These findings demonstrate that PTCY-Tac offers effective GVHD prevention and favorable outcomes in MMUD allo-HCT, supporting its application for patients without fully matched donors.