Post-transplant cyclophosphamide improves survival compared to antithymocyte globulin in HLA-mismatched unrelated donor stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from mismatched unrelated donors (MMUD) carries high risks of non-relapse mortality (NRM) and graft-versus-host disease (GVHD). Post-transplant cyclophosphamide (PTCY) has emerged as an alternative to antithymocyte globulin (ATG) for GVHD prophylaxis. This single-center retrospective study compared PTCY (n=41) to high-dose ATG and low-dose ATG in 155 MMUD alloHSCT recipients. PTCY was associated with better OS with one-year OS of 78.7% vs. 56.5% in PTCY and HD groups (p=0.007) and vs 64.8% in LD group (p=0.059), driven by a significant reduction in NRM (p=0.008), with a one-year NRM in the PTCY group at 7.7% vs 24.4% in the HD group (p=0.031) and 29.8% in the LD group (p=0.026). The relapse incidence was similar between the groups (17.5% vs. 25.7% and 16.2% for PTCY, HD and LD group, p=0.830), despite a better PFS in the PTCY group (p=0.034) with one-year PFS at 78.4% vs. 50.0% in HD group (p=0.002) and 54.0% in LD group (p=0.041). Day-100 grade II-IV and grade III-IV acute GVHD, as well as one-year chronic GVHD and moderate/severe chronic GVHD were not significantly different. However, one-year GVHD-related mortality was lower in the PTCY group (2.6% vs. 14.4% and 14.9%, p=0.018). Infection-related mortality was similar across groups, but CMV and EBV infections were less frequent with PTCY, potentially linked to differences in immune reconstitution. PTCY prophylaxis was associated with improved OS, PFS, and lower NRM compared to HD and LD ATG in MMUD alloHSCT.