Author(s): Cooley S, Trachtenberg E, Bergemann TL, Saeteurn K, Klein J,
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Abstract Survival for patients with acute myeloid leukemia (AML) is limited by treatment-related mortality (TRM) and relapse after unrelated donor (URD) hematopoietic cell transplantation (HCT). Natural killer (NK)-cell alloreactivity, determined by donor killer-cell immunoglobulin-like receptors (KIRs) and recipient HLA, correlates with successful HCT for AML. Hypothesizing that donor KIR genotype (A/A: 2 A KIR haplotypes; B/x: at least 1 B haplotype) would affect outcomes, we genotyped donors and recipients from 209 HLA-matched and 239 mismatched T-replete 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 = .007). Multivariate analysis demonstrated a 30\% improvement in the relative risk of relapse-free survival with B/x donors compared with A/A donors (RR: 0.70 [95\% CI: 0.55-0.88]; P = .002). B/x donors were associated with a higher incidence of chronic graft-versus-host disease (GVHD; RR: 1.51 [95\% CI: 1.01-2.18]; P = .03), but not of acute GVHD, relapse, or TRM. This analysis demonstrates that unrelated donors with KIR B haplotypes confer significant survival benefit to patients undergoing T-replete HCT for AML. KIR genotyping of prospective donors, in addition to HLA typing, should be performed to identify HLA-matched donors with B KIR haplotypes.
This article was published in Blood
and referenced in Journal of Clinical & Cellular Immunology