期刊
BLOOD
卷 139, 期 10, 页码 1452-1468出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2021013443
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资金
- National Institutes of Health (NIH), National Cancer Institute (NCI) [AI069197, CA100019, CA218285]
- Public Health Service from the NIH/NCI [U24CA076518]
- NIH/National Heart, Lung and Blood Institute (NHLBI)
- NIH/National Institute of Allergy and Infectious Diseases (NIAID) from the Health Resources and Services Administration (HRSA) [HHSH250201700006C]
- Office of Naval Research [N00014-20-1-2705, N00014-20-1-2832]
- Biomedical Advanced Research and Development Authority (BARDA)
- Be the Match Foundation
- Medical College of Wisconsin the National Marrow Donor Program
- Actinium Pharmaceuticals, Inc
- Adienne SA
- Allovir, Inc
- Amgen, Inc
- Angiocrine Bioscience
- Astellas Pharma US
- bluebird bio, Inc
- Bristol Myers Squibb Co
- Celgene Corp
- CSL Behring
- CytoSen Therapeutics, Inc.
- Daiichi Sankyo Co, Ltd
- ExcellThera
- Fate Therapeutics
- GamidaCell, Ltd
- Genentech, Inc
- Incyte Corporation
- Janssen/Johnson Johnson
- Jazz Pharmaceuticals, Inc
- Kiadis Pharma
- Kite, a Gilead Company
- Kyowa Kirin
- Legend Biotech
- Magenta Therapeutics
- Merck Sharp Dohme Corp
- Millennium, the Takeda Oncology Co
- Miltenyi Biotec, Inc
- Novartis Pharmaceuticals Corporation
- Omeros Corporation
- Oncoimmune, Inc
- Orca Biosystems, Inc
- Pfizer, Inc
- Pharmacyclics, LLC
- Sanofi Genzyme
- Stemcyte
- Takeda Pharma
- Vor Biopharma
- Xenikos BV
- [R01AI128775]
- [R01HL130388]
HLA factors play an important role in the success of haploidentical transplantation. Disease-free survival is associated with matching status at individual HLA loci, with HLA-DRB1 and -DPB1 mismatches and HLA-C,-B leader, and -DQB1 matching being favorable. Considering HLA factors may help optimize the selection of haploidentical related donors.
Hematopoietic cell transplantation from HLA-haploidentical related donors is increasingly used to treat hematologic cancers; however, characteristics of the optimal haploidentical donor have not been established. We studied the role of donor HLA mismatching in graft-versus-host disease (GVHD), disease recurrence, and survival after haploidentical donor transplantation with posttransplantation cyclophosphamide (PTCy) for 1434 acute leukemia or myelodysplastic syndrome patients reported to the Center for International Blood and Marrow Transplant Research. The impact of mismatching in the graft-versus-host vector for HLA-A, -B, -C, -DRB1, and -DQB1 alleles, theHLA-B leader, and HLA-DPB1 T-cell epitope (TCE) were studied using multivariable regression methods. Outcome was associated with HLA (mis)matches at individual loci rather than the total number of HLA mismatches. HLA-DRB1 mismatches were associated with lower risk of disease recurrence. HLA-DRB1 mismatching with HLA-DQB1 matching correlated with improved disease-free survival. HLA-B leader matching and HLA-DPB1 TCE-nonpermissive mismatching were each associated with improved overall survival. HLA-C matching lowered chronic GVHD risk, and the level of HLA-C expression correlated with transplant-related mortality. Matching status at the HLA-B leader and HLA-DRB1,-DQB1, and -DPB1 predicted disease-free survival, as did patient and donor cytomegalovirus serostatus, patient age, and comorbidity index. A web-based tool was developed to facilitate selection of the best haploidentical-related donor by calculating disease-free survival based on these characteristics. In conclusion, HLA factors influence the success of haploidentical transplantation with PTCy. HLA-DRB1 and -DPB1 mismatching and HLA-C,-B leader, and -DQB1 matching are favorable. Consideration of HLA factors may help to optimize the selection of haploidentical related donors.
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