Systematic evaluation of donor-KIR/recipient-HLA interactions in HLA-matched hematopoietic cell transplantation for AML

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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-HLAC1+ 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.

Original languageEnglish
Pages (from-to)581-590
Number of pages10
JournalBlood advances
Volume8
Issue number3
DOIs
StatePublished - 13 Feb 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 by The American Society of Hematology.

Funding

J.A.F. received support from a Hematology Opportunities for the Next Generation of Research Scientists award from the American Society of Hematology.

FundersFunder number
American Society of Hematology

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