Tools for optimizing risk assessment in hematopoietic cell transplant - What can we get away with?

Unrelated allogeneic hematopoietic cell transplant (HCT) is a critical modality to treat hematologic malignancies. The current objective of donor selection is to match donor and recipient at the HLA (human leukocyte antigen) peptide-binding region which should lower the risk of graft-versus-host disease. However, depending on the patient's ethnicity/race, finding a matched donor is challenging, especially for HLA-DPB1 which is due to the weak linkage disequilibrium between HLA-DPB1 and the other HLA class II loci. Recent evidence, on the molecular level, has shown that certain HLA mismatches carry lower clinical risk. More specifically, there is an increasing understanding of polymorphisms of the innate and adaptive immune systems and their impact on transplant outcomes, allowing us to expand our "toolkit" for optimization of donor selection in HCT. Therefore, in this review we discuss matching strategies based on comparing donor and recipient polymorphisms that may influence innate and adaptive immune response genes in allorecognition and the role of single nucleotide polymorphisms in non-HLA genes that have the potential for providing additional tools to refine risk stratification.