Donor KIR3DL1, HLA-B Subtypes Associated With AML HCT Outcomes
KIR3DL1 and HLA-B subtypes mediate NK cell activity against acute myelogenous leukemia and are associated with relapse and mortality after allogeneic hematopoietic cell transplantation.
KIR3DL1 and HLA-B subtypes mediate NK cell activity against acute myelogenous leukemia (AML) and are associated with relapse and mortality after allogeneic hematopoietic cell transplantation (HCT), according to a study published in the Journal of Clinical Oncology.1
Donor NK cell activity is known to help control AML relapse after HCT. Killer immunoglobulin-like receptors (KIRs) mediate NK activity by an inhibitory function and are highly polymorphic. The purpose of this study was to determine if KIR3DL1 polymorphic subtypes with differences in NK inhibition are associated with relapse after HCT.
Blood samples were collected from 1328 patients with AML who received an allograft 9/10 or 10/10 HLA-matched unrelated donor. Analyses included KIR and KIR3DL1 typing, cell sorting, and in vitro cytotoxicity.
Combinations of donor KIR3DL1 and HLA-B subtypes predicted to have weak inhibition or non-inhibition of NK cells were significantly associated with lower relapse (hazard ratio [HR], 0.72; P = .004) and lower overall mortality (HR, 0.84; P = .030) compared with subtypes with strong inhibitory activity.
High-risk patients with all KIR ligands demonstrated the greatest effect on relapse (HR, 0.54; P < .001) and mortality (HR, 0.74; P < .008).
Weak and non-inhibitory KIR3DL1 and HLA-B subtypes were additive to the effects of patient KIR2DS1.
The risk of failure was lowest among patients with the KIR3DL1-N+HLA-Bw4 combination, in which NK cells were educated but refractory to inhibition.
Intermediate relapse and mortality risk was predicted by B26 donor-patient pairs and Bw4-80T+KIR3DL1-H and Bw4-80I+KIR3DL1-L partnerships. Bw4-80I+KIR3DL1-H and Bw4-80T+KIR3DL1-L predicted a high risk of relapse and mortality.
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The results of this study suggest that among patients with AML, “refining donor selection algorithms to include KIR3DL1/HLA-B subtype analysis to avoid strong inhibition donors may reduce relapse and improve survival,” wrote the authors.
- Boudreau JE, Giglio F, Gooley TA, et al. KIR3DL1/HLA-B subtypes govern acute myelogenous leukemia relapse after hematopoietic cell transplantation. J Clin Oncol. 2017 May 18. doi: 10.1200/JCO.2016.70.7059 [Epub ahead of print]