期刊
TRANSPLANTATION AND CELLULAR THERAPY
卷 27, 期 2, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2020.10.010
关键词
Hematopoietic cell transplant (HCT); Allogeneic HCT; Human leukocyte antigen (HLA); HLA heterozygosity; HLA supertypes
资金
- National Institutes of Health (NIH) [U01 AI069197]
- Leukemia & Lymphoma Society
- Cancer Center Core grant [NIH P30 CA008748]
- Public Health Service [U24CA076518]
- National Cancer Institute (NCI)
- National Heart, Lung and Blood Institute (NHLBI)
- National Institute of Allergy and Infectious Diseases (NIAID) [U24HL138660]
- NHLBI [HHSH250201700006C, SC1MC31881-01-00, HHSH250201700007C]
- NCI [OT3HL147741, R21HL140314, U01HL128568]
- Health Resources and Services Administration (HRSA) [N00014-181-2850, N00014-18-1-2888, N00014-20-1-2705]
- Office of Naval Research [P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01HL126589, R01AI128775, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612]
- BARDA
- Match Foundation
- Boston Children's Hospital
- St. Baldrick's Foundation
- National Marrow Donor Program
- Medical College of Wisconsin
- Adaptive Biotechnologies
- Adienne SA
- Anthem, Inc.
- Astellas Pharma US
- bluebird bio, Inc.
- Celgene Corp.
- Gamida-Cell, Ltd.
- Genzyme
- HistoGenetics, Inc.
- Incyte Corporation
- Janssen Biotech, Inc.
- Janssen Pharmaceuticals, Inc.
- Janssen/Johnson Johnson
- Jazz Pharmaceuticals, Inc.
- Kiadis Pharma
- Kite Pharma
- Kyowa Kirin
- Magenta Therapeutics
- Medac GmbH
- Merck Company, Inc.
- Merck Sharp Dohme Corp.
- Mesoblast
- Takeda Oncology Co.
- Miltenyi Biotec, Inc.
- Novartis Oncology
- Novartis Pharmaceuticals Corporation
- Omeros Corporation
- Phamacyclics, LLC
- REGiMMUNE Corp.
- Sanofi Genzyme
- Takeda Oncology
- Takeda Pharma
Diversity in HLAs does not significantly impact outcomes post-allogeneic HCT, but certain HLA supertypes are associated with transplant-related mortality and disease-free survival. Further investigation into the role of specific HLA supertypes in transplant outcomes is warranted based on these findings.
Maximizing the probability of antigen presentation to T cells through diversity in HLAs can enhance immune responsiveness and translate into improved clinical outcomes, as evidenced by the association of heterozygosity and supertypes at HLA class I loci with improved survival in patients with advanced solid tumors treated with immune checkpoint inhibitors. We investigated the impact of HLA heterozygosity, supertypes, and surface expression on outcomes in adult and pediatric patients with acute myeloid leukemia (AML), myelodysplastic syndrome, acute lymphoblastic leukemia, and non-Hodgkin lymphoma who underwent 8/8 HLA-matched, T cell replete, unrelated, allogeneic hematopoietic cell transplant (HCT) from 2000 to 2015 using patient data reported to the Center for International Blood and Marrow Transplant Research. HLA class I heterozygosity and HLA expression were not associated with overall survival, relapse, transplant-related mortality (TRM), disease-free survival (DFS), and acute graft-versus-host disease following HCT. The HLA-B62 supertype was associated with decreased TRM in the entire patient cohort (hazard ratio [HR], 0.79; 95% CI, 0.69 to 0.90; P = .00053). The HLA-B27 supertype was associated with worse DFS in patients with AML (HR = 1.21; 95% CI, 1.10 to 1.32; P = .00005). These findings suggest that the survival benefit of HLA heterozygosity seen in solid tumor patients receiving immune checkpoint inhibitors does not extend to patients undergoing allogeneic HCT. Certain HLA supertypes, however, are associated with TRM and DFS, suggesting that similarities in peptide presentation between supertype members play a role in these outcomes. Beyond implications for prognosis following HCT, these findings support the further investigation of these HLA supertypes and the specific immune peptides important for transplant outcomes. (C) 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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