Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 21, Issue 9, Pages 1589-1596Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2015.05.002
Keywords
Killer immunoglobulin-like receptor (KIR); Reduced-intensity conditioning; HCT; AML/MDS
Categories
Funding
- Public Health Service from the National Cancer Institute [U24-CA076518]
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases
- National Heart, Lung, and Blood Institute [5U10HL069294]
- National Cancer Institute
- Health Resources and Services Administration [HHSH250201200016C]
- Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]
- Actinium Pharmaceuticals
- Allos Therapeutics, Inc.
- Amgen
- 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
- Leukemia & Lymphoma Society
- Medac GmbH
- 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
- WellPoint
- Anonymous donation to the Medical College of Wisconsin
Ask authors/readers for more resources
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 CURD) 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 Ha recapitulate some but not all KIR-HLA effects observed in myeloablative HCT. (C) 2015 American Society for Blood and Marrow Transplantation.
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