Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia

Abstract

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.