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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study</title>
<author><name sortKey="Fleischhauer, Katharina" sort="Fleischhauer, Katharina" uniqKey="Fleischhauer K" first="Katharina" last="Fleischhauer">Katharina Fleischhauer</name>
</author>
<author><name sortKey="Shaw, Bronwen E" sort="Shaw, Bronwen E" uniqKey="Shaw B" first="Bronwen E" last="Shaw">Bronwen E. Shaw</name>
</author>
<author><name sortKey="Gooley, Theodore" sort="Gooley, Theodore" uniqKey="Gooley T" first="Theodore" last="Gooley">Theodore Gooley</name>
</author>
<author><name sortKey="Malkki, Mari" sort="Malkki, Mari" uniqKey="Malkki M" first="Mari" last="Malkki">Mari Malkki</name>
</author>
<author><name sortKey="Bardy, Peter" sort="Bardy, Peter" uniqKey="Bardy P" first="Peter" last="Bardy">Peter Bardy</name>
</author>
<author><name sortKey="Bignon, Jean Denis" sort="Bignon, Jean Denis" uniqKey="Bignon J" first="Jean-Denis" last="Bignon">Jean-Denis Bignon</name>
</author>
<author><name sortKey="Dubois, Valerie" sort="Dubois, Valerie" uniqKey="Dubois V" first="Valérie" last="Dubois">Valérie Dubois</name>
</author>
<author><name sortKey="Horowitz, Mary M" sort="Horowitz, Mary M" uniqKey="Horowitz M" first="Mary M" last="Horowitz">Mary M. Horowitz</name>
</author>
<author><name sortKey="Madrigal, J Alejandro" sort="Madrigal, J Alejandro" uniqKey="Madrigal J" first="J Alejandro" last="Madrigal">J Alejandro Madrigal</name>
</author>
<author><name sortKey="Morishima, Yasuo" sort="Morishima, Yasuo" uniqKey="Morishima Y" first="Yasuo" last="Morishima">Yasuo Morishima</name>
</author>
<author><name sortKey="Oudshoorn, Machteld" sort="Oudshoorn, Machteld" uniqKey="Oudshoorn M" first="Machteld" last="Oudshoorn">Machteld Oudshoorn</name>
</author>
<author><name sortKey="Ringden, Olle" sort="Ringden, Olle" uniqKey="Ringden O" first="Olle" last="Ringden">Olle Ringden</name>
</author>
<author><name sortKey="Spellman, Stephen" sort="Spellman, Stephen" uniqKey="Spellman S" first="Stephen" last="Spellman">Stephen Spellman</name>
</author>
<author><name sortKey="Velardi, Andrea" sort="Velardi, Andrea" uniqKey="Velardi A" first="Andrea" last="Velardi">Andrea Velardi</name>
</author>
<author><name sortKey="Zino, Elisabetta" sort="Zino, Elisabetta" uniqKey="Zino E" first="Elisabetta" last="Zino">Elisabetta Zino</name>
</author>
<author><name sortKey="Petersdorf, Effie W" sort="Petersdorf, Effie W" uniqKey="Petersdorf E" first="Effie W" last="Petersdorf">Effie W. Petersdorf</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22340965</idno>
<idno type="pmc">3813000</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813000</idno>
<idno type="RBID">PMC:3813000</idno>
<idno type="doi">10.1016/S1470-2045(12)70004-9</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">001D87</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D87</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study</title>
<author><name sortKey="Fleischhauer, Katharina" sort="Fleischhauer, Katharina" uniqKey="Fleischhauer K" first="Katharina" last="Fleischhauer">Katharina Fleischhauer</name>
</author>
<author><name sortKey="Shaw, Bronwen E" sort="Shaw, Bronwen E" uniqKey="Shaw B" first="Bronwen E" last="Shaw">Bronwen E. Shaw</name>
</author>
<author><name sortKey="Gooley, Theodore" sort="Gooley, Theodore" uniqKey="Gooley T" first="Theodore" last="Gooley">Theodore Gooley</name>
</author>
<author><name sortKey="Malkki, Mari" sort="Malkki, Mari" uniqKey="Malkki M" first="Mari" last="Malkki">Mari Malkki</name>
</author>
<author><name sortKey="Bardy, Peter" sort="Bardy, Peter" uniqKey="Bardy P" first="Peter" last="Bardy">Peter Bardy</name>
</author>
<author><name sortKey="Bignon, Jean Denis" sort="Bignon, Jean Denis" uniqKey="Bignon J" first="Jean-Denis" last="Bignon">Jean-Denis Bignon</name>
</author>
<author><name sortKey="Dubois, Valerie" sort="Dubois, Valerie" uniqKey="Dubois V" first="Valérie" last="Dubois">Valérie Dubois</name>
</author>
<author><name sortKey="Horowitz, Mary M" sort="Horowitz, Mary M" uniqKey="Horowitz M" first="Mary M" last="Horowitz">Mary M. Horowitz</name>
</author>
<author><name sortKey="Madrigal, J Alejandro" sort="Madrigal, J Alejandro" uniqKey="Madrigal J" first="J Alejandro" last="Madrigal">J Alejandro Madrigal</name>
</author>
<author><name sortKey="Morishima, Yasuo" sort="Morishima, Yasuo" uniqKey="Morishima Y" first="Yasuo" last="Morishima">Yasuo Morishima</name>
</author>
<author><name sortKey="Oudshoorn, Machteld" sort="Oudshoorn, Machteld" uniqKey="Oudshoorn M" first="Machteld" last="Oudshoorn">Machteld Oudshoorn</name>
</author>
<author><name sortKey="Ringden, Olle" sort="Ringden, Olle" uniqKey="Ringden O" first="Olle" last="Ringden">Olle Ringden</name>
</author>
<author><name sortKey="Spellman, Stephen" sort="Spellman, Stephen" uniqKey="Spellman S" first="Stephen" last="Spellman">Stephen Spellman</name>
</author>
<author><name sortKey="Velardi, Andrea" sort="Velardi, Andrea" uniqKey="Velardi A" first="Andrea" last="Velardi">Andrea Velardi</name>
</author>
<author><name sortKey="Zino, Elisabetta" sort="Zino, Elisabetta" uniqKey="Zino E" first="Elisabetta" last="Zino">Elisabetta Zino</name>
</author>
<author><name sortKey="Petersdorf, Effie W" sort="Petersdorf, Effie W" uniqKey="Petersdorf E" first="Effie W" last="Petersdorf">Effie W. Petersdorf</name>
</author>
</analytic>
<series><title level="j">The lancet oncology</title>
<idno type="ISSN">1470-2045</idno>
<idno type="eISSN">1474-5488</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p id="P2"><bold>Background</bold>
The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation.</p>
<p id="P3"><bold>Methods</bold>
HLA and clinical data for unrelated-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients and unrelated donors matching status were classified as HLA-DPB1 match, non-permissive HLA-DPB1 mismatch (those with mismatched T-cell-epitope groups), or permissive HLA-DPB1 mismatch (those with matched T-cell-epitope groups). The clinical outcomes assessed were overall mortality, non-relapse mortality, relapse, and severe (grade 3–4) acute graft-versus-host disease (aGvHD).</p>
<p id="P4"><bold>Findings</bold>
Of 8539 transplantations, 5428 (64%) were matched for ten of ten HLA alleles (HLA 10/10 matched) and 3111 (36%) for nine of ten alleles (HLA 9/10 matched). Of the group overall, 1719 (20%) were HLA-DPB1 matches, 2670 (31%) non-permissive HLA-DPB1 mismatches, and 4150 (49%) permissive HLA-DPB1 mismatches. In HLA 10/10-matched transplantations, non-permissive mismatches were associated with a significantly increased risk of overall mortality (hazard ratio [HR] 1·15, 95% CI 1·05–1·25; p=0·002), non-relapse mortality (1·28, 1·14–1·42; p<0·0001), and severe aGvHD (odds ratio [OR] 1·31, 95% CI 1·11–1·54; p=0·001), but not relapse (HR 0·89, 95% CI 0·77–1·02; p=0·10), compared with permissive mismatches. There were significant differences between permissive HLA-DPB1 mismatches and HLA-DPB1 matches in terms of non-relapse mortality (0·86, 0·75–0·98; p=0·03) and relapse (1·34, 1·17–1·54; p<0·0001), but not for overall mortality (0·96, 0·87–1·06; p=0·40) or aGvHD (OR 0·84, 95% CI 0·69–1·03; p=0·09). In the HLA 9/10 matched population, non-permissive HLA-DPB1 mismatches also increased the risk of overall mortality (HR 1·10, 95% CI 1·00–1·22; p=0·06), non-relapse mortality (1·19, 1·05–1·36; p=0·007), and severe aGvHD (OR 1·37, 95% CI 1·13–1·66; p=0·002) compared with permissive mismatches, but the risk of relapse was the same in both groups (HR 0·93, 95% CI 0·78–1·11; p=0·44). Outcomes for HLA 10/10-matched transplantations with non-permissive HLA-DPB1 mismatches did not differ substantially from those for HLA 9/10-matched transplantations with permissive HLA-DPB1 mismatches or HLA-DPB1 matches.</p>
<p id="P5"><bold>Interpretation</bold>
T-cell-epitope matching defines permissive and non-permissive HLA-DPB1 mismatches. Avoidance of an unrelated donor with a non-permissive T-cell-epitope mismatch at HLA-DPB1 might provide a practical clinical strategy for lowering the risks of mortality after unrelated-donor haemopoietic-cell transplantation.</p>
<p id="P6"><bold>Funding</bold>
National Institutes of Health; Associazione Italiana per la Ricerca sul Cancro; Telethon Foundation; Italian Ministry of Health; Cariplo Foundation; National Cancer Institute; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; Office of Naval Research; IRGHET Paris; Swedish Cancer Society; Children's Cancer Foundation; Swedish Research Council; Cancer Society in Stockholm; Karolinska Institutet; and Leukemia and Lymphoma Society.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">100957246</journal-id>
<journal-id journal-id-type="pubmed-jr-id">27004</journal-id>
<journal-id journal-id-type="nlm-ta">Lancet Oncol</journal-id>
<journal-id journal-id-type="iso-abbrev">Lancet Oncol.</journal-id>
<journal-title-group><journal-title>The lancet oncology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1470-2045</issn>
<issn pub-type="epub">1474-5488</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22340965</article-id>
<article-id pub-id-type="pmc">3813000</article-id>
<article-id pub-id-type="doi">10.1016/S1470-2045(12)70004-9</article-id>
<article-id pub-id-type="manuscript">NIHMS493351</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Fleischhauer</surname>
<given-names>Katharina</given-names>
</name>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Shaw</surname>
<given-names>Bronwen E</given-names>
</name>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gooley</surname>
<given-names>Theodore</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Malkki</surname>
<given-names>Mari</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Bardy</surname>
<given-names>Peter</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Bignon</surname>
<given-names>Jean-Denis</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Dubois</surname>
<given-names>Valérie</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Horowitz</surname>
<given-names>Mary M</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Madrigal</surname>
<given-names>J Alejandro</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Morishima</surname>
<given-names>Yasuo</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Oudshoorn</surname>
<given-names>Machteld</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Ringden</surname>
<given-names>Olle</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Spellman</surname>
<given-names>Stephen</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Velardi</surname>
<given-names>Andrea</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Zino</surname>
<given-names>Elisabetta</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Petersdorf</surname>
<given-names>Effie W</given-names>
</name>
</contrib>
<on-behalf-of>on behalf of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation</on-behalf-of>
</contrib-group>
<aff id="A1">Unit of Molecular and Functional Immunogenetics, Division of Regenerative Medicine, Stem Cells and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) H San Raffaele, Milan, Italy (K Fleischhauer MD, E Zino BSc); Haemato-Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research, London, UK (B E Shaw MD); Anthony Nolan Research Institute, Royal Free Hospital, London, UK (B E Shaw, Prof J A Madrigal MD); Fred Hutchinson Cancer Research Center, Seattle, WA, USA (Prof T Gooley PhD, M Malkki PhD, Prof E W Petersdorf MD); Transplant Services Laboratory, Australian Red Cross Blood Service, Melboune, Victoria, Australia (P Bardy MD); Cancer Services Central Adelaide Local Health Network, Royal Adelaide Hospital, Adelaide, SA, Australia (P Bardy); HLA Laboratory, Établissement Français du Sang, Nantes, France (J-D Bignon MD); HLA Laboratory, Établissement Français du Sang, Lyon, France (V Dubois BSc); Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA (Prof M M Horowitz MD); Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA (S Spellman MBS)<bold>; Aichi Cancer Center, Nagoya, Japan</bold>
(Prof Y Morishima MD)<bold>; Japan Marrow Donor Program, Tokyo, Japan</bold>
(Prof Y Morishima); Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands (M Oudshoorn PhD)<bold>Europdonor Foundation, Leiden, Netherlands</bold>
(M Oudshoorn PhD); Division of Clinical Immunology and Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden (Prof O Ringden MD); and Division of Haematology and Clinical Immunology, University of Perugia, Perugia, Italy (Prof A Velardi MD)</aff>
<author-notes><corresp id="CR1">Correspondence to: Dr Bronwen Shaw, Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, Hampstead, London, NW3 2QG, UK <bold><email>bshaw@doctors.org.uk</email>
</bold>
</corresp>
<fn id="FN1"><label>*</label>
<p id="P1">These authors contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>9</day>
<month>7</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>15</day>
<month>2</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub"><month>4</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>30</day>
<month>10</month>
<year>2013</year>
</pub-date>
<volume>13</volume>
<issue>4</issue>
<elocation-id>10.1016/S1470-2045(12)70004-9</elocation-id>
<abstract><title>Summary</title>
<p id="P2"><bold>Background</bold>
The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation.</p>
<p id="P3"><bold>Methods</bold>
HLA and clinical data for unrelated-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients and unrelated donors matching status were classified as HLA-DPB1 match, non-permissive HLA-DPB1 mismatch (those with mismatched T-cell-epitope groups), or permissive HLA-DPB1 mismatch (those with matched T-cell-epitope groups). The clinical outcomes assessed were overall mortality, non-relapse mortality, relapse, and severe (grade 3–4) acute graft-versus-host disease (aGvHD).</p>
<p id="P4"><bold>Findings</bold>
Of 8539 transplantations, 5428 (64%) were matched for ten of ten HLA alleles (HLA 10/10 matched) and 3111 (36%) for nine of ten alleles (HLA 9/10 matched). Of the group overall, 1719 (20%) were HLA-DPB1 matches, 2670 (31%) non-permissive HLA-DPB1 mismatches, and 4150 (49%) permissive HLA-DPB1 mismatches. In HLA 10/10-matched transplantations, non-permissive mismatches were associated with a significantly increased risk of overall mortality (hazard ratio [HR] 1·15, 95% CI 1·05–1·25; p=0·002), non-relapse mortality (1·28, 1·14–1·42; p<0·0001), and severe aGvHD (odds ratio [OR] 1·31, 95% CI 1·11–1·54; p=0·001), but not relapse (HR 0·89, 95% CI 0·77–1·02; p=0·10), compared with permissive mismatches. There were significant differences between permissive HLA-DPB1 mismatches and HLA-DPB1 matches in terms of non-relapse mortality (0·86, 0·75–0·98; p=0·03) and relapse (1·34, 1·17–1·54; p<0·0001), but not for overall mortality (0·96, 0·87–1·06; p=0·40) or aGvHD (OR 0·84, 95% CI 0·69–1·03; p=0·09). In the HLA 9/10 matched population, non-permissive HLA-DPB1 mismatches also increased the risk of overall mortality (HR 1·10, 95% CI 1·00–1·22; p=0·06), non-relapse mortality (1·19, 1·05–1·36; p=0·007), and severe aGvHD (OR 1·37, 95% CI 1·13–1·66; p=0·002) compared with permissive mismatches, but the risk of relapse was the same in both groups (HR 0·93, 95% CI 0·78–1·11; p=0·44). Outcomes for HLA 10/10-matched transplantations with non-permissive HLA-DPB1 mismatches did not differ substantially from those for HLA 9/10-matched transplantations with permissive HLA-DPB1 mismatches or HLA-DPB1 matches.</p>
<p id="P5"><bold>Interpretation</bold>
T-cell-epitope matching defines permissive and non-permissive HLA-DPB1 mismatches. Avoidance of an unrelated donor with a non-permissive T-cell-epitope mismatch at HLA-DPB1 might provide a practical clinical strategy for lowering the risks of mortality after unrelated-donor haemopoietic-cell transplantation.</p>
<p id="P6"><bold>Funding</bold>
National Institutes of Health; Associazione Italiana per la Ricerca sul Cancro; Telethon Foundation; Italian Ministry of Health; Cariplo Foundation; National Cancer Institute; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; Office of Naval Research; IRGHET Paris; Swedish Cancer Society; Children's Cancer Foundation; Swedish Research Council; Cancer Society in Stockholm; Karolinska Institutet; and Leukemia and Lymphoma Society.</p>
</abstract>
<funding-group><award-group><funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source>
<award-id>U01 AI069197 || AI</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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