Increased Donor Inhibitory KIR Are Associated with Reduced GVHD and Improved Survival Following HLA Matched Unrelated Donor HCT in Pediatric Acute Leukemia

Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after hematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting. Pediatric acute leukemia patients were retrospectively analyzed and KIR-KIRL combinations and maximal inhibitory KIR ligand (IM-KIR) scores determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints, remained significant for relevant downstream events. KIR-KIRL combinations were significantly predictive for reduced grade 3-4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM-KIR=5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse-free survival, GRFS, and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the pediatric acute leukemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in pediatric recipients with acute leukemia to optimize clinical outcomes.