Interrogating the impact of KIR ligand mismatch in engraftment following HLA-disparate stem cell transplantation

Abstract

The effects of donor-derived natural killer (NK) cell alloreactivity on disease relapse and transplant-related mortality following allogeneic stem cell transplantation have been described while the impact of recipient-derived NK cell alloreactivity on donor engraftment is not well known. Epitopes of HLA Class I molecules act as ligands for NK cell killer immunoglobulin-like receptors (KIR) regulating their cytotoxicity. As such, NK cell alloreactivity is predictable from KIR ligand mismatches between donors and recipients. We analyzed the impact of KIR ligand mismatch (KIR-L-MM) on donor engraftment in 70 cord blood transplants (CBT) and 26 haploidentical transplants (HaploSCT). In CBT, host-versus-graft-directed KIR-L-MM predicted primary graft failure; an effect not mitigated by use of ATG. This trend was most significant with HLA-C KIR-L-MM. In addition, graft-versus-host-directed KIR-L-MM predicted the dominant cord blood unit in double CBT. In the limited HaploSCT cohort, host-versus-graft-directed KIR-L-MM did not predict graft failure. Time to neutrophil engraftment was unaffected by KIR-L-MM in either CBT or HaploSCT. The direction of KIR-L mismatch may be a parameter to consider when selecting CBT units to ensure successful engraftment. The role of KIR-L-MM in CBT and HaploSCT engraftment merits further exploration in a large transplant database.