HLA Class I Mismatches Reduce Survival after HCT in the Ptcy Era: A Study By the EBMT Cellular Therapy and Immunobiology Working Party

Introduction: Human leukocyte antigen (HLA) compatibility between patient and donor is a mainstay in allogeneic hematopoietic cell transplantation (HCT) to reduce the risk of potentially fatal graft-versus-host disease (GvHD). Traditionally, mismatches at HLA class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DRB1) have been associated with significantly reduced overall survival (OS) and increased risks of non-relapse mortality (NRM) and acute (a)GvHD compared to fully matched donors (Lee et al. Blood 2007). This has resulted in a preference for 8/8 (10/10 in Europe) HLA-matched donors in unrelated HCT (Dehn et al. Blood 2019). More recently, interest in expanding the donor pool to patients lacking a fully matched donor (Shaw et al. JCO 2021 &TCT 2023) and advances in the management and prevention of GvHD, in particular with post-transplant cyclophosphamide (PTCy) (Bolaños-Meade et al. NEJM 2023), are increasing the use of mismatched (i.e.