Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric allogeneic hematopoietic stem-cell transplantation

Abstract

Purpose: Killer-cell immunoglobulin-like receptors (KIRs) that regulate natural-killer cells are highly polymorphic. Some KIR2DL1 alleles encode receptors that have stronger signaling function than others. We tested the hypothesis that the clinical outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT) could be affected by donor KIR2DL1 polymorphism. Patients and Methods: All 313 pediatric patients received allogeneic HSCT at a single institution. Donor KIR2DL1 functional allele typing was retrospectively performed using single nucleotide polymorphism assay. Results: Patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R245) had better survival (P = .0004) and lower cumulative incidence of disease progression (P = .001) than those patients who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C245). The effect of KIR2DL1 allelic polymorphism was similar in patients with acute myeloid leukemia or acute lymphoblastic leukemia among all allele groups (P ≥ .71). Patients who received a KIR2DL1-R245-positive graft with HLA-C receptor-ligand mismatch had the best survival (P = .00003) and lowest risk of leukemia progression (P = .0005) compared with those who received a KIR2DL1-C245 homozygous graft. Conclusion: Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.