Faculty Collaboration Database

Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood 2010 Oct 07;116(14):2411-9

Date

06/29/2010

Pubmed ID

20581313

Pubmed Central ID

PMC2953880

DOI

10.1182/blood-2010-05-283051

Scopus ID

2-s2.0-77957734984 (requires institutional sign-in at Scopus site)   491 Citations

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.

Author List

Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, Marsh SG, Geraghty D, Spellman S, Haagenson MD, Ladner M, Trachtenberg E, Parham P, Miller JS

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Child
Child, Preschool
Disease-Free Survival
Donor Selection
Genetic Loci
Genotype
Hematopoietic Stem Cell Transplantation
Humans
Infant
Killer Cells, Natural
Leukemia, Myeloid, Acute
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Receptors, KIR
Young Adult