Faculty Collaboration Database

Systematic evaluation of donor-KIR/recipient-HLA interactions in HLA-matched hematopoietic cell transplantation for AML. Blood Adv 2024 Feb 13;8(3):581-590

Date

12/06/2023

Pubmed ID

38052043

Pubmed Central ID

PMC10837477

DOI

10.1182/bloodadvances.2023011622

Scopus ID

2-s2.0-85185534011 (requires institutional sign-in at Scopus site)   1 Citation

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.

Author List

Fein JA, Shouval R, Krieger E, Spellman SR, Wang T, Baldauf H, Fleischhauer K, Kröger N, Horowitz M, Maiers M, Miller JS, Mohty M, Nagler A, Weisdorf D, Malmberg KJ, Toor AA, Schetelig J, Romee R, Koreth J

Authors

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Chronic Disease
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Receptors, KIR
Recurrence
Unrelated Donors