Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia
Institution: | University of Minnesota |
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Department: | Clinical Research |
Degree: | MS |
Year: | 2009 |
Keywords: | Unrelated donor (URD); Acute Myeloid Leukemia (AML); Immunoglobulin-like receptors; Toxicity; Clinical Research |
Record ID: | 1854782 |
Full text PDF: | http://purl.umn.edu/59769 |
University of Minnesota M.S. thesis. November 2009. Major: Clinical Research. Advisors: Jeffrey S Miller, MD, Daniel J Weisdorf, MD, Chap T Le, PhD. 1 computer file (PDF); iv, 36 pages, appendix 29-36. Survival after unrelated donor (URD) hematopoietic cell transplantation (HCT) for Acute Myeloid Leukemia (AML) is limited by toxicity and relapse. Killer-cell immunoglobulin-like receptors (KIR) control NK cell alloreactivity after HCT. Hypothesizing that donor KIR genotype (A/A: 2 A KIR haplotypes; B/x: ≥ 1 B haplotype) would affect outcomes, we genotyped donors and recipients from 448 URD transplantations for AML. Three year overall survival was significantly higher after transplantation from a KIR B/x donor (31% [95% CI: 26-36] vs. 20% [95% CI: 13-27]; p = 0.007). Multivariate analysis demonstrated a 30% better relative risk of relapse-free survival with B/x vs. A/A donors (RR 0.70 [95% CI 0.55-0.88]; p=.002). B/x donors were associated with more chronic GVHD (RR 1.51 [95% CI 1.01-2.18]; p=.03), but not more acute GVHD, relapse or treatment-related mortality. This analysis demonstrates that HCT from unrelated donors with KIR B haplotypes confers significant survival benefit for patients with AML.