KIR in Allogeneic Hematopoietic Stem Cell Transplantation: Need for a Unified Paradigm for Donor Selection

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a lifesaving therapy for hematological malignancies. For years, a fully matched HLA donor was a requisite for the procedure. However, new immunosuppressive strategies have enabled the recruitment of viable alternative donors, particularly haploidentical donors. Over 95% of patients have at least two potential haploidentical donors available to them. To identify the best haploidentical donor, the assessment of new immunogenetic criteria could help. To this end, the clinical benefit of KIR genotyping in aHSCT has been widely studied but remains contentious. This review aims to evaluate the importance of KIR-driven NK cell alloreactivity in the context of aHSCT and explain potential reasons for the discrepancies in the literature. Here, through a non-systematic review, we highlight how the studies in this field and their respective predictive models or scoring strategies could be conceptually opposed, explaining why the role of NK cells remains unclear in aHCST outcomes. We evaluate the limitations of each published prediction model and describe how every scoring strategy to date only partly delivers the requirements for optimally effective NK cells in aHSCT. Finally, we propose approaches toward finding the optimal use of KIR genotyping in aHSCT for a unified criterion for donor selection.