Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation

Ronald M. Sobecks, Tao Wang, Medhat Askar, Meighan M. Gallagher, Michael Haagenson, Stephen Spellman, Marcelo Fernandez-Vina, Karl Johan Malmberg, Carlheinz Müller, Minoo Battiwalla, James Gajewski, Michael R. Verneris, Olle Ringdén, Susana Marino, Stella Davies, Jason Dehn, Martin Bornhäuser, Yoshihiro Inamoto, Ann Woolfrey, Peter ShawMarilyn Pollack, Daniel Weisdorf, Jeffrey Milller, Carolyn Hurley, Stephanie J. Lee, Katharine Hsu

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P =002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2+ patients. AML patients with KIR2DS1+, HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = 002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.

Original languageEnglish (US)
Pages (from-to)1589-1596
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2015

Bibliographical note

Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute , the National Heart, Lung, and Blood Institute , and the National Institute of Allergy and Infectious Diseases ; a Grant/Cooperative Agreement 5U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute ; a contract HHSH250201200016C with Health Resources and Services Administration; 2 grants ( N00014-13-1-0039 and N00014-14-1-0028 ) from the Office of Naval Research ; and grants from Actinium Pharmaceuticals ; Allos Therapeutics, Inc. ; Amgen ; Anonymous donation to the Medical College of Wisconsin ; Ariad ; Be The Match Foundation ; Blue Cross and Blue Shield Association ; Celgene Corporation ; Chimerix, Inc. ; Fred Hutchinson Cancer Research Center ; Fresenius-Biotech North America, Inc. ; Gamida Cell Teva Joint Venture Ltd. ; Genentech, Inc. ; Gentium SpA ; Genzyme Corporation ; GlaxoSmithKline ; Health Research, Inc. ; Roswell Park Cancer Institute ; HistoGenetics ; Incyte Corporation ; Jeff Gordon Children's Foundation ; Kiadis Pharma ; The Leukemia & Lymphoma Society ; Medac GmbH ; The Medical College of Wisconsin ; Merck & Co, Inc. ; Millennium: The Takeda Oncology Co. ; Milliman USA, Inc. ; Miltenyi Biotec, Inc. ; NMDP ; Onyx Pharmaceuticals ; Optum Healthcare Solutions, Inc. ; Osiris Therapeutics ; Otsuka America Pharmaceutical, Inc. ; Perkin Elmer, Inc. ; Remedy Informatics ; Sanofi US ; Seattle Genetics ; Sigma-Tau Pharmaceuticals ; Soligenix, Inc. ; St. Baldrick's Foundation ; StemCyte, A Global Cord Blood Therapeutics Co. ; Stemsoft Software, Inc. ; Swedish Orphan Biovitrum ; Tarix Pharmaceuticals ; Terumo BCT ; Teva Neuroscience, Inc. ; Therakos ; University of Minnesota ; University of Utah ; and WellPoint . The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the U.S. Government.

Keywords

  • AML/MDS
  • Killer immunoglobulin-like receptor (KIR)
  • Reduced-intensity conditioning HCT

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