Journal
BLOOD
Volume 122, Issue 22, Pages 3651-3658Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-05-501510
Keywords
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Categories
Funding
- National Cancer Institute (NCI) [U24-CA076518]
- National Heart, Lung, and Blood Institute (NHLBI)
- National Institute of Allergy and Infectious Diseases (NIAID)
- NHLBI [5U10HL069294]
- NCI
- Health Resources and Services Administration [HHSH250201200016C]
- Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]
- Office of Naval Research
- Actinium Pharmaceuticals
- Allos Therapeutics, Inc.
- Amgen, Inc.
- Ariad
- Be the Match Foundation
- Blue Cross and Blue Shield Association
- Celgene Corporation
- 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, Inc.
- 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.
- National Marrow Donor Program
- Onyx Pharmaceuticals
- Optum Healthcare Solutions, Inc.
- Osiris Therapeutics, Inc.
- Otsuka America Pharmaceutical, Inc.
- PerkinElmer, Inc.
- Remedy Informatics
- Sanofi US
- Seattle Genetics
- Sigma-tau Pharmaceuticals
- Soligenix, Inc.
- St. Baldrick's Foundation
- StemCyte
- Global Cord Blood Therapeutics Co.
- Stemsoft Software, Inc.
- Swedish Orphan Biovitrum
- Tarix Pharmaceuticals
- TerumoBCT
- Teva Neuroscience, Inc.
- THERAKOS, Inc.
- University of Minnesota
- University of Utah
- Wellpoint, Inc.
Ask authors/readers for more resources
HLA disparity has a negative impact on the outcomes of hematopoietic cell transplantation (HCT). We studied the independent impact of amino acid substitution (AAS) at peptide-binding positions 9, 99, 116, and 156, and killer immunoglobulin-like receptor binding position 77 of HLA-A, B, or C, on the risks for grade 3-4 acute graft-versus-host disease (GVHD), chronic GVHD, treatment-related mortality (TRM), relapse, and overall survival. In multivariate analysis, a mismatch at HLA-C position 116 was associated with increased risk for severe acute GVHD (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.15-1.82, P = .0016). Mismatch at HLA-C position 99 was associated with increased transplant-related mortality (HR = 1.37, 95% CI = 1.1-1.69, P = .0038). Mismatch at HLA-B position 9 was associated with increased chronic GVHD (HR = 2.28, 95% CI = 1.36-3.82, P = .0018). No AAS were significantly associated with outcome at HLA-A. Specific AAS pair combinations with a frequency > 30 were tested for association with HCT outcomes. Cysteine to tyrosine substitution at position 99 of HLA-C was associated with increased TRM (HR = 1.78, 95% = CI 1.27-2.51, P = .0009). These results demonstrate that donor-recipient mismatch for certain peptide-binding residues of the HLA class I molecule is associated with increased risk for acute and chronic GVHD and death.
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