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 overall survival with a 1-year overall survival of 78.7% versus 56.5% in the PTCY and high-dose ATG groups (P=0.007) and 64.8% in the low-dose ATG group (P=0.059), driven by a significant reduction in NRM (P=0.008), with a 1-year NRM in the PTCY group of 7.7% versus 24.4% in the high-dose ATG group (P=0.031) and 29.8% in the low-dose group (P=0.026). The relapse incidence was similar between the groups (17.5% vs. 25.7% and 16.2% for the PTCY, high-dose ATG and low-dose ATG groups, respectively; P=0.830), despite a better progression-free survival in the PTCY group (P=0.034) with 1-year progression-free survival being 78.4% compared with 50.0% in the high-dose ATG group (P=0.002) and 54.0% in the low-dose group (P=0.041). Day-100 grade II-IV and grade III-IV acute GvHD, as well as 1-year chronic GvHD and moderate/severe chronic GvHD were not significantly different. However, 1-year GvHD-related mortality was lower in the PTCY group (2.6% vs. 14.4% and 14.9% in the high- and low-dose ATG groups, respectively; P=0.018). Infection-related mortality was similar across groups, but cytomegalovirus and Epstein-Barr virus infections were less frequent with PTCY, a finding potentially linked to differences in immune reconstitution. Compared to high-dose and low-dose ATG, PTCY prophylaxis was associated with improved overall survival and progression-free survival as well as lower NRM in MMUD alloHSCT.