Post-transplantation cyclophosphamide and antithymocyte globulin in 8/10 HLA-mismatched unrelated donor transplantation: the analysis on behalf of the transplant complications working party of the EBMT.

Allogeneic hematopoietic cell transplantation (alloHCT) from 8/10 HLA-matched unrelated donor is performed in a minority of patients. There is little data on its outcomes and consequently, guidelines on optimal transplantation procedures are lacking. The Transplant complications working party of the EBMT performed a registry study comparing approaches to graft-versus-host disease (GVHD) prophylaxis in recipients of alloHCT from 8/10 HLA-mismatched unrelated donors (8/10 MMUD). The analysis included 450 adult patients with hematological malignancies receiving a first alloHCT between 2015 and 2021, GVHD prophylaxis strategies included ATG in 318 and PTCy in 132 patients. AlloHCT from 8/10 MMUD resulted in 21.1% non-relapse mortality, 28.5% cumulative incidence of relapse, 55.7% overall survival (OS), 50.4% progression-free-survival and 39.8% GVHD-relapse-free survival (GRFS). PTCy decreased the risk of grade II-IV (HR 0.63, 95%CI 0.40-0.99) and III-IV acute GVHD (HR 0.31, 95%CI 0.13-0.74), improved OS (HR 0.63, 95%CI 0.41-0.95) and GRFS (HR 0.65, 95%CI 0.47-0.91). No other differences between the groups were documented. Transplantation from female donors to male recipients increased the incidence of extensive chronic GVHD (HR 2.39, 95%CI 1.10-5.19) and decreased PFS (HR 1.49, 95%CI 1.01-2.20). AlloHCT from 8/10 HLA-matched unrelated donor is feasible and the use of PTCy in GVHD prophylaxis improves outcomes.