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Role of HLA-B exon ...
Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation : a retrospective cohort study
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- Petersdorf, Effie W. (author)
- Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA;Univ Washington, Dept Med, Seattle, WA USA
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- Carrington, Mary (author)
- Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA;MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Harvard Univ, Cambridge, MA 02138 USA
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- O'hUigin, Colm (author)
- Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA
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- Bengtsson, Mats (author)
- Uppsala universitet,Klinisk immunologi
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- De Santis, Dianne (author)
- Fiona Stanley Hosp, PathWest, Perth, WA, Australia
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- Dubois, Valerie (author)
- Etab Francais Sang Auvergne Rhone Alpes, Site De Lyon, Decines, France
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- Gooley, Ted (author)
- Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA
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- Horowitz, Mary (author)
- Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA;Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA
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- Hsu, Katharine (author)
- Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA
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- Madrigal, J. Alejandro (author)
- Royal Free Hosp, Anthony Nolan Res Inst, London, England
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- Maiers, Martin J. (author)
- Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA
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- Malkki, Mari (author)
- Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA
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- McKallor, Caroline (author)
- Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA
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- Morishima, Yasuo (author)
- Aichi Med Univ, Sch Med, Nagakute, Aichi, Japan
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- Oudshoorn, Machteld (author)
- Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands;Matchis Fdn, Leiden, Netherlands
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- Spellman, Stephen R. (author)
- Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA
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- Villard, Jean (author)
- Geneva Univ Hosp, Geneva, Switzerland
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- Stevenson, Phil (author)
- Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA
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(creator_code:org_t)
- ELSEVIER SCI LTD, 2020
- 2020
- English.
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In: The Lancet Haematology. - : ELSEVIER SCI LTD. - 2352-3026. ; 7:1, s. E50-E60
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Background: The success of unrelated haemopoietic cell transplantation (HCT) is limited by graft-versus-host disease (GVHD), which is the main post-transplantation challenge when HLA-matched donors are unavailable. A sequence dimorphism in exon 1 of HLA-B gives rise to leader peptides containing methionine (Met; M) or threonine (Thr; T), which differentially influence natural killer and T-cell alloresponses. The main aim of the study was to evaluate the role of the leader dimorphism in GVHD after HLA-B-mismatched unrelated HCT.Methods: We did a retrospective cohort study of 33 982 patients who received an unrelated HCT done in Australia, Europe, japan, North America, and the UK between jan 1, 1988, and Dec 31, 2016. Data were contributed by participants of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation. All cases were included and there were no exclusion criteria. Multivariate regression models were used to assess risks associated with HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 mismatching. Among the 33 982 transplantations, the risks of GVHD associated with HLA-B M and T leaders were established in 17 100 (50.3%) HLA-matched and 1457 (4.3%) single HLA-B-mismatched transplantations using multivariate regression models. Leader frequencies were defined in 2 004 742 BeTheMatch US registry donors.Findings: Between jan 20, 2017, and March 11, 2019, we assessed 33 982 HCTs using multivariate regression models for the role of HLA mismatching on outcome. Median follow-up was 1841 days (IQR 909-2963). Mortality and GVHD increased with increasing numbers of HLA mismatches. A single HLA-B mismatch increased grade 3-4 acute GVHD (odds ratio [OR] 1.89, 95% CI 1. 53-2.33; p<0.0001). Among the single HLA-B-mismatched transplantations, acute GVHD risk was higher with leader mismatching than with leader matching (OR 1.73, 1.02-2.94; p=0 .042 for grade 2-4) and with an M leader shared allotype compared with a T leader shared allotype (OR 1.98, 1.39-2.81; p=0.0001 for grade 3-4). The preferred HLA-B-mismatched donor is leader-matched and shares a T leader allotype. The majority (1836 939 [91.6%]) of the 2004742 US registry donors have the TT or MT genotype.Interpretation: The HLA-B leader informs GVHD risk after HLA-B-mismatched unrelated HCT and differentiates high-risk HLA-B mismatches from those with lower risk. The leader of the matched allotype could be considered to be as important as the leader of the mismatched allotype for GVHD. Prospective identification of leader-matched donors is feasible for most patients in need of a HCT, and could lower GVHD and increase availability of HCT therapy. These findings are being independently validated and warrant further research in prospective trials.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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Petersdorf, Effi ...
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Carrington, Mary
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O'hUigin, Colm
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Bengtsson, Mats
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De Santis, Diann ...
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Dubois, Valerie
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Gooley, Ted
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Horowitz, Mary
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Hsu, Katharine
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Madrigal, J. Ale ...
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Maiers, Martin J ...
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Malkki, Mari
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McKallor, Caroli ...
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Morishima, Yasuo
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Oudshoorn, Macht ...
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Spellman, Stephe ...
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Villard, Jean
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Stevenson, Phil
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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The Lancet Haema ...
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Uppsala University