Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia.
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.
Cooley
Sarah
S
Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
Weisdorf
Daniel J
DJ
Guethlein
Lisbeth A
LA
Klein
John P
JP
Wang
Tao
T
Le
Chap T
CT
Marsh
Steven G E
SG
Geraghty
Daniel
D
Spellman
Stephen
S
Haagenson
Michael D
MD
Ladner
Martha
M
Trachtenberg
Elizabeth
E
Parham
Peter
P
Miller
Jeffrey S
JS
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
D054340:Receptors, KIR