Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia

Blood - Tập 116 - Trang 2411-2419 - 2010
Sarah Cooley1, Daniel J. Weisdorf1, Lisbeth A. Guethlein2, John P. Klein3, Tao Wang3, Chap T. Le4, Steven G.E. Marsh5, Daniel Geraghty6, Stephen Spellman7, Michael D. Haagenson8, Martha Ladner9, Elizabeth Trachtenberg9, Peter Parham2, Jeffrey S. Miller1
1Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis;
2Structural Biology, Stanford University, CA;
3Biostatistics, Medical College of Wisconsin, Milwaukee;
4Biostatistics, University of Minnesota, Minneapolis;
5Anthony Nolan Research Institute and University College London, London, United Kingdom;
6Fred Hutchinson Cancer Center, Seattle, WA
7National Marrow Donor Program, Minneapolis, MN
8Center for International Blood and Marrow Transplant Research, Minneapolis, MN; and
9Children's Hospital & Research Center, Oakland, CA

Tóm tắt

AbstractKiller-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.

Tài liệu tham khảo

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