GVHD risk assessment beyond current HLA evaluation

Abstract

As one of the most clinically validated immunotherapies to date, allogeneic haemopoietic cell transplantation (HCT) is a potentially curative option for blood cancers via the graft-versus-leukaemia effect. However, T-cell reactivity to alloantigens in normal host tissues also gives rise to graft-versus-host disease (GVHD), particularly in transplantation recipients from unrelated donors, accounting for more than 20% of deaths in patients who have a HCT. To limit GVHD, clinicians have been matching the patients and the unrelated donor graft the best they can using HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1. However, this matching is not always possible, particularly for patients of non-white backgrounds who are not well represented in the donor registry. HCT from donors with one HLA mismatch followed by standard GVHD prophylaxis can be done, but is often followed by severe acute GVHD. The question of why is addressed by Effie Petersdorf and colleagues in The Lancet Haematology.