Effect of Donor KIR2DL1 Allelic Polymorphism on the Outcome of Pediatric Allogeneic Hematopoietic Stem-Cell Transplantation

<jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> All 313 pediatric patients received allogeneic HSCT at a single institution. Donor KIR2DL1 functional allele typing was retrospectively performed using single nucleotide polymorphism assay. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R<jats:sup>245</jats:sup>) 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-C<jats:sup>245</jats:sup>). 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-R<jats:sup>245</jats:sup>–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-C<jats:sup>245</jats:sup> homozygous graft. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection. </jats:p></jats:sec>