Systematic evaluation of donor-KIR/recipient-HLA interactions in HLA-matched hematopoietic cell transplantation for AML
Year: 2023
Type: article
Study design: Observational Study
Abstract: ABSTRACT: In acute myeloid leukemia (AML), donor natural killer cell killer immunoglobulin-like receptors (KIR) and recipient HLA interactions may contribute to the graft-versus-leukemia effect of allogeneic hematopoietic cell transplantation (HCT). Analyses of individual KIR/HLA interactions, however, have yielded conflicting findings, and their importance in the HLA-matched unrelated donor (MUD) setting remains controversial. We systematically studied outcomes of individual donor-KIR/recipient-HLA interactions for HCT outcomes and empirically evaluated prevalent KIR genotypes for clinical benefit. Adult patients with AML (n = 2025) who received HCT with MUD grafts in complete remission reported to the Center for International Blood and Marrow Transplantation were evaluated. Only the donor-2DL2+/recipient-HLA-C1+ pair was associated with reduced relapse (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67-0.93; P = .006) compared with donor-2DL2-/recipient-HLA-C1+ pair. However, no association was found when comparing HLA-C groups among KIR-2DL2+-graft recipients. We identified 9 prevalent donor KIR genotypes in our cohort and screened them for association with relapse risk. Genotype 5 (G5) in all recipients and G3 in Bw4+ recipients were associated with decreased relapse risk (HR, 0.52; 95% CI, 0.35-0.78; P = .002; and HR, 0.32; 95% CI, 0.14-0.72; P = .006; respectively) and G2 (HR 1.63, 95% CI, 1.15-2.29; P = .005) with increased relapse risk in C1-homozygous recipients, compared with other patients with the same ligand. However, we could not validate these findings in an external data set of 796 AML transplants from the German transplantation registry. Neither a systematic evaluation of known HLA-KIR interactions nor an empiric assessment of prevalent KIR genotypes demonstrated clinically actionable associations; therefore, these data do not support these KIR-driven strategies for MUD selection in AML.
Source: Blood Advances
Authors: Joshua A. Fein, Roni Shouval, Elizabeth Krieger, Stephen R. Spellman, Tao Wang, Henning Baldauf, Katharina Fleischhauer, Nicolaus Kröger, Mary Horowitz, Martin Maiers, Jeffrey S Miller, Mohamad Mohty, Arnon Nagler, Daniel Weisdorf, Karl-Johan Malmberg, Amir A. Toor, Johannes Schetelig, Rizwan Romee, John Koreth
Institutions: NewYork–Presbyterian Hospital, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, Virginia Commonwealth University, Children's Hospital of Richmond at VCU, National Marrow Donor Program, Medical College of Wisconsin, Essen University Hospital, University Medical Center Hamburg-Eppendorf, University of Minnesota, Sorbonne Université, Hôpital Saint-Antoine, Sheba Medical Center, Oslo University Hospital, Lehigh Valley Health Network, Technische Universität Dresden, Harvard University, Dana-Farber Cancer Institute
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funder: National Cancer Institute
OpenAlex ID: W4389329622