Systematic Evaluation of Donor-KIR/Recipient-HLA Interactions in HLA-matched Hematopoietic Cell Transplantation for AML

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Joshua Alexander Fein - , New York Presbyterian Hospital (Autor:in)
  • Roni Shouval - , Memorial Sloan-Kettering Cancer Center (Autor:in)
  • Elizabeth Krieger - , Virginia Commonwealth University in Qatar (Autor:in)
  • Stephen R Spellman - , CIBMTR® (Center for International Blood and Marrow Transplant Research) (Autor:in)
  • Tao Wang - , Medical College of Wisconsin (Autor:in)
  • Henning Baldauf - , DKMS Donor Center gGmbH (Autor:in)
  • Katharina Fleischhauer - , LVR-Universitätsklinik Essen (Autor:in)
  • Nicolaus Kröger - , Universitätsklinikum Hamburg-Eppendorf (UKE) (Autor:in)
  • Mary M Horowitz - , Medical College of Wisconsin (Autor:in)
  • Martin Maiers - , National Marrow Donor Program (Autor:in)
  • Jeffrey S Miller - , Klinik u. Poliklinik f. Dermatologie u. Venerologie (Autor:in)
  • Mohamad Mohty - , Hôpital Saint-Antoine (Autor:in)
  • Arnon Nagler - , Chaim Sheba Medical Center (Autor:in)
  • Daniel J Weisdorf - , Minnesota State University Moorhead (Autor:in)
  • Karl-Johan Malmberg - , Universitätsklinikum Oslo (Autor:in)
  • Amir Ahmed Toor - , Lehigh Valley Health Network (Autor:in)
  • Johannes Schetelig - , Medizinische Klinik und Poliklinik I, DKMS Donor Center gGmbH (Autor:in)
  • Rizwan Romee - , Harvard University (Autor:in)
  • John Koreth - , Dana-Farber Cancer Institute (Autor:in)

Abstract

In acute myeloid leukemia (AML), donor NK-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 AML patients (n=2025) transplanted in complete remission who received MUD grafts reported to the Center for International Blood and Marrow Transplantation were evaluated. Only the donor-2DL2present/recipient-HLA-C1present pair was associated with reduced relapse (hazard ratio 0.79 [95% confidence interval: 0.67, 0.93], p = 0.006) compared with donor-2DL2absent/recipient-HLA-C1present. However, no association were found when comparing HLA-C groups among KIR-2DL2present-graft recipients. We identified nine prevalent donor KIR genotypes in our cohort and screened them for association with relapse risk. Genotype (G)5 in all recipients and G3 in Bw4present recipients were associated with decreased relapse risk (HR 0.52 [0.35, 0.78], p = 0.002; 0.32 [0.14, 0.72], p = 0.006, respectively) and G2 (HR 1.63 [1.15, 2.29], p = 0.005) with increased relapse risk C1-homozygous recipients, compared to patients with the same ligand. However, we could not validate these findings in an external dataset 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 not supporting these KIR-driven strategies for MUD selection in AML.

Details

OriginalspracheEnglisch
FachzeitschriftBlood advances
PublikationsstatusElektronische Veröffentlichung vor Drucklegung - 5 Dez. 2023
Peer-Review-StatusJa

Externe IDs

unpaywall 10.1182/bloodadvances.2023011622
Scopus 85185534011

Schlagworte