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Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation

  1. Author:
    Petersdorf, Effie W
    Bengtsson, Mats
    De Santis, Dianne
    Dubois, Valerie
    Fleischhauer, Katharina
    Gooley, Ted
    Horowitz, Mary
    Madrigal, J Alejandro
    Malkki, Mari
    McKallor, Caroline
    Morishima, Yasuo
    Oudshoorn, Machteld
    Spellman, Stephen R
    Villard, Jean
    Stevenson, Phil
    Carrington,Mary

  2. Author Address

    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA., Department of Medicine, University of Washington, Seattle, WA., Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden., PathWest, Fiona Stanley Hospital, Perth, WA, Australia., Etablissement Fran 231;ais du Sang Auvergne Rh 244;ne Alpes, site de Lyon, D 233;cines, France., Institute for Experimental Cellular Therapy, University of Duisburg-Essen, Essen, Germany., Center for International Blood and Marrow Transplant Research, Milwaukee, WI., Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI., Anthony Nolan Research Institute, Royal Free Hospital, London, United Kingdom., Aichi Medical University School of Medicine, Nagakute, Aichi, Japan., Leiden University Medical Centre, Department Immunohematology and Blood Transfusion, Leiden, the Netherlands., Matchis Foundation, Leiden, the Netherlands., Center for International Blood and Marrow Transplant Research, Minneapolis, MN., Geneva University Hospital, Geneva, Switzerland., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD., Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA.,
    1. Year: 2020
    2. Date: AUG 20
    3. Epub Date: 2020 06 01
  2. Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
    1. 38
    2. 24
    3. Pages: 2712-+
  4. Type of Article: Article
  5. Article Number: JCO2000265
  6. ISSN: 0732-183X
  1. Abstract:

    Purpose: The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1-matched and -mismatched unrelated donors. Patients and methods: Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1-matched or -mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient's mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients. Results: In HLA-A, -B, -C, -DRB1,-DQB1-matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; P = .001) and severe acute GVHD (OR, 1.32; P = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor's mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient's mismatched HLA-DPB1 allotype. Conclusion: The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1-matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.

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External Sources

  1. View Full Text
  2. DOI: 10.1200/JCO.20.00265
  3. PMID: 32479188
  4. View record in Web of Science®
  5. WOS: 000563289600004

Library Notes

  1. Fiscal Year: FY2019-2020
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