1. Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation: a retrospective cohort study
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Effie W Petersdorf, Mary Carrington, Colm O'hUigin, Mats Bengtsson, Dianne De Santis, Valerie Dubois, Ted Gooley, Mary Horowitz, Katharine Hsu, J Alejandro Madrigal, Martin J Maiers, Mari Malkki, Caroline McKallor, Yasuo Morishima, Machteld Oudshoorn, Stephen R Spellman, Jean Villard, Phil Stevenson, Martin Maiers, Stephen Spellman, Jane Apperley, Peter Bardy, Ghislaine Bernard, Yves Bertrand, Adrian Bloor, Chiara Bonini, Stephane Buhler, Laura Bungener, Helen Campbell, Kristina Carlson, Ben Carpenter, Anne Cesbron, Christian Chabannon, Yves Chalandon, Jeremy Chapman, Réda Chebel, Patrice Chevallier, Gerda Choi, Matt Collin, Jan J Cornelissen, Charles Crawley, Lloyd D'Orsogna, Jean-Hugues Dalle, Eric Deconinck, Muriel DeMatteis, Mary Diviney, Anne Dormoy, Katia Gagne, Brenda Gibson, Maria Gilleece, David Gottlieb, John Gribben, Tayfun Güngör, Mike Haagenson, Cathie Hart, Rhonda Holdsworth, Ian Humphreys, Yoshihisa Kodera, Mickey Koh, Hélène Labussière-Wallet, Arjan C Lankester, Neubery Lardy, Sarah Lawson, Xavier Leleu, Stephen MacKinnon, Ram Malladi, Steven GE Marsh, Murray Martin, Neema P Mayor, I Grant McQuaker, Ellen Meijer, Satoko Morishima, Emmanouil Nikolousis, Kim Orchard, Jacob Passweg, Amit Patel, Katherine Patrick, Béatrice Pedron, Andy Peniket, Julia Perry, Eefke Petersen, Victoria Potter, Mike Potter, Rachel Protheroe, Nicole Raus, Carmen Ruiz de Elvira, Nigel Russell, Nicholaas PM Schaap, Urs Schanz, Harry Schouten, Roderick Skinner, John Snowden, Eric Spierings, Colin Steward, Eleni Tholouli, Alycia Thornton, Marcel Tilanus, Arnold van de Meer, Hendrik Veelkens, Paul Veys, Narelle Watson, Lyanne Weston, Keith Wilson, Marie Wilson, Robert Wynn, József Zsiros, University of Washington [Seattle], Harvard University [Cambridge], Frederick National Laboratory for Cancer Research (FNLCR), Uppsala Universitet [Uppsala], PathWest Murdoch / Fiona Stanley Hospital [Perth, WA, Australia] (PMFSH), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical College of Wisconsin [Milwaukee] (MCW), Memorial Sloane Kettering Cancer Center [New York], Royal Free Hospital [London, UK], Center for International Blood and Marrow Transplant Research [Minneapolis, MN, USA] (CIBMTR), Aichi Medical University School of Medicine [Nagakute, Aichi, Japan] (AMUSM), Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Geneva University Hospital (HUG), International Histocompatibility Working Group in Hematopoietic Cell Transplantation: Effie W Petersdorf, Mary Carrington, Colm O'hUigin, Mats Bengtsson, Dianne De Santis, Valerie Dubois, Ted Gooley, Mary Horowitz, Katharine Hsu, J Alejandro Madrigal, Martin Maiers, Mari Malkki, Caroline McKallor, Yasuo Morishima, Machteld Oudshoorn, Stephen Spellman, Jean Villard, Phil Stevenson, Jane Apperley, Peter Bardy, Ghislaine Bernard, Yves Bertrand, Adrian Bloor, Chiara Bonini, Stephane Buhler, Laura Bungener, Helen Campbell, Kristina Carlson, Ben Carpenter, Anne Cesbron, Christian Chabannon, Yves Chalandon, Jeremy Chapman, Réda Chebel, Patrice Chevallier, Gerda Choi, Matt Collin, Jan J Cornelissen, Charles Crawley, Lloyd D'Orsogna, Jean-Hugues Dalle, Eric Deconinck, Muriel DeMatteis, Mary Diviney, Anne Dormoy, Katia Gagne, Brenda Gibson, Maria Gilleece, David Gottlieb, John Gribben, Tayfun Güngör, Mike Haagenson, Cathie Hart, Rhonda Holdsworth, Ian Humphreys, Yoshihisa Kodera, Mickey Koh, Hélène Labussière-Wallet, Arjan C Lankester, Neubery Lardy, Sarah Lawson, Xavier Leleu, Stephen MacKinnon, Ram Malladi, Steven Ge Marsh, Murray Martin, Neema P Mayor, I Grant McQuaker, Ellen Meijer, Satoko Morishima, Emmanouil Nikolousis, Kim Orchard, Jacob Passweg, Amit Patel, Katherine Patrick, Béatrice Pedron, Andy Peniket, Julia Perry, Eefke Petersen, Victoria Potter, Mike Potter, Rachel Protheroe, Nicole Raus, Carmen Ruiz de Elvira, Nigel Russell, Nicholaas Pm Schaap, Urs Schanz, Harry Schouten, Roderick Skinner, John Snowden, Eric Spierings, Colin Steward, Eleni Tholouli, Alycia Thornton, Marcel Tilanus, Arnold van de Meer, Hendrik Veelkens, Paul Veys, Narelle Watson, Lyanne Weston, Keith Wilson, Marie Wilson, Robert Wynn, József Zsiros, Leiden University Medical Center (LUMC), GAGNE, Katia, CCA - Cancer Treatment and quality of life, AII - Inflammatory diseases, Hematology, CCA - Cancer biology and immunology, Petersdorf, E. W., Carrington, M., O'Huigin, C., Bengtsson, M., De Santis, D., Dubois, V., Gooley, T., Horowitz, M., Hsu, K., Madrigal, J. A., Maiers, M. J., Malkki, M., Mckallor, C., Morishima, Y., Oudshoorn, M., Spellman, S. R., Villard, J., Stevenson, P., Maiers, M., Spellman, S., Apperley, J., Bardy, P., Bernard, G., Bertrand, Y., Bloor, A., Bonini, C., Buhler, S., Bungener, L., Campbell, H., Carlson, K., Carpenter, B., Cesbron, A., Chabannon, C., Chalandon, Y., Chapman, J., Chebel, R., Chevallier, P., Choi, G., Collin, M., Cornelissen, J. J., Crawley, C., D'Orsogna, L., Dalle, J. -H., Deconinck, E., Dematteis, M., Diviney, M., Dormoy, A., Gagne, K., Gibson, B., Gilleece, M., Gottlieb, D., Gribben, J., Gungor, T., Haagenson, M., Hart, C., Holdsworth, R., Humphreys, I., Kodera, Y., Koh, M., Labussiere-Wallet, H., Lankester, A. C., Lardy, N., Lawson, S., Leleu, X., Mackinnon, S., Malladi, R., Marsh, S. G., Martin, M., Mayor, N. P., Mcquaker, I. G., Meijer, E., Morishima, S., Nikolousis, E., Orchard, K., Passweg, J., Patel, A., Patrick, K., Pedron, B., Peniket, A., Perry, J., Petersen, E., Potter, V., Potter, M., Protheroe, R., Raus, N., Ruiz de Elvira, C., Russell, N., Schaap, N. P., Schanz, U., Schouten, H., Skinner, R., Snowden, J., Spierings, E., Steward, C., Tholouli, E., Thornton, A., Tilanus, M., van de Meer, A., Veelkens, H., Veys, P., Watson, N., Weston, L., Wilson, K., Wilson, M., Wynn, R., Zsiros, J., RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: DA TI Staf (9), University of Zurich, and Petersdorf, Effie W
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Oncology ,Male ,Hematopoietic Stem Cell Transplantation/methods ,[SDV]Life Sciences [q-bio] ,2720 Hematology ,Graft vs Host Disease ,Histocompatibility Testing ,0302 clinical medicine ,Graft vs Host Disease/genetics ,immune system diseases ,unrelated donor ,Exons/genetics ,graft-versus-host disease ,Medicine ,ddc:616 ,Hematopoietic Stem Cell Transplantation ,Exons ,Hematology ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Histocompatibility ,HLA-B Antigens/genetics ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,EXPRESSION ,Adult ,medicine.medical_specialty ,Adolescent ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,610 Medicine & health ,Human leukocyte antigen ,Lower risk ,Risk Assessment ,Article ,Graft vs Host Disease/genetics/immunology ,03 medical and health sciences ,Internal medicine ,Journal Article ,Humans ,Retrospective Studies ,RECEPTOR ,business.industry ,MORTALITY ,RECOGNITION ,Retrospective cohort study ,Odds ratio ,medicine.disease ,Transplantation ,Graft-versus-host disease ,hematopoietic-cell transplantation ,SEQUENCE-DERIVED PEPTIDES ,10036 Medical Clinic ,HLA-B Antigens ,10032 Clinic for Oncology and Hematology ,Multivariate Analysis ,RESIDUES ,HLA-B leader ,business ,030215 immunology - Abstract
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
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- 2021