title: Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia.
abstract: Killer-cell immunoglobulin-like receptor (KIR) genes form a diverse, immunogenetic system. Group A and B KIR haplotypes have distinctive centromeric (Cen) and telomeric (Tel) gene-content motifs. Aiming to develop a donor selection strategy to improve transplant outcome, we compared the contribution of these motifs to the clinical benefit conferred by B haplotype donors. We KIR genotyped donors from 1409 unrelated transplants for acute myelogenous leukemia (AML; n = 1086) and acute lymphoblastic leukemia (ALL; n = 323). Donor KIR genotype influenced transplantation outcome for AML but not ALL. Compared with A haplotype motifs, centromeric and telomeric B motifs both contributed to relapse protection and improved survival, but Cen-B homozygosity had the strongest independent effect. With Cen-B/B homozygous donors the cumulative incidence of relapse was 15.4% compared with 36.5% for Cen-A/A donors (relative risk of relapse 0.34; 95% confidence interval 0.2-0.57; P < .001). Overall, significantly reduced relapse was achieved with donors having 2 or more B gene-content motifs (relative risk 0.64; 95% confidence interval 0.48-0.86; P = .003) for both HLA-matched and mismatched transplants. KIR genotyping of several best HLA-matched potential unrelated donors should substantially increase the frequency of transplants by using grafts with favorable KIR gene content. Adopting this practice could result in superior disease-free survival for patients with AML.
authors.affiliation: Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.forename: John P
authors.initials: JP
authors.lastname: Klein
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Chap T
authors.initials: CT
authors.lastname: Le
authors.forename: Steven G E
authors.initials: SG
authors.lastname: Marsh
authors.forename: Daniel
authors.initials: D
authors.lastname: Geraghty
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Haagenson
authors.forename: Martha
authors.initials: M
authors.lastname: Ladner
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D046148:Donor Selection; D056426:Genetic Loci; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000601:surgery / Q000628:therapy; D054340:Receptors, KIR / Q000235:genetics*; D055815:Young Adult
chemical_list: D054340:Receptors, KIR