HLA typing—A case-based approach to donor selection

In the early years of hematopoietic cell transplantation (HCT), matching of patients and donors was poorly understood and complications related to genetic (especially HLA) mismatching were profound, resulting in a very high incidence of fatal graft-versus-host disease (GVHD). This essentially limited the choice of a donor to a sibling, and as the understanding of HLA improved, defined the donor as an HLA-identical sibling. As patient outcomes improved, the use of an unrelated donor (URD) became more common. Later, with the advent of URD registries and improved HLA typing techniques, the use of an URD overtook that of an HLA-identical sibling in frequency both in Europe and in the United States (US). Increasing confidence in our ability to manage and prevent the immune complications of HCT led to the use of HLA-mismatched donors being expanded, in the setting of umbilical cord blood (UCB) and haploidentical transplantation. In 2018, it is unusual for a patient not to go to transplant due to the lack of a suitable donor option. In this manuscript, we describe the impact of genetic factors, in particular HLA, and the technologies for typing these, on the outcomes of HCT. We highlight both well-accepted donor selection practices and newer or more controversial advances in donor selection.