Biological significance of HLA locus matching in unrelated donor bone marrow transplantation
We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell–replete marrow from...
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| Veröffentlicht in: | Blood 2015-02, Vol.125 (7), p.1189-1197 |
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| creator | Morishima, Yasuo Kashiwase, Koichi Matsuo, Keitaro Azuma, Fumihiro Morishima, Satoko Onizuka, Makoto Yabe, Toshio Murata, Makoto Doki, Noriko Eto, Tetsuya Mori, Takehiko Miyamura, Koichi Sao, Hiroshi Ichinohe, Tatsuo Saji, Hiroo Kato, Shunichi Atsuta, Yoshiko Kawa, Keisei Kodera, Yoshihisa Sasazuki, Takehiko |
| description | We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell–replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.
•Significant HLA locus mismatches responsible for transplant-related events were determined in 7898 unrelated marrow donor transplants.•This information provides a rationale for use of an algorithm for unrelated donor selection. |
| doi_str_mv | 10.1182/blood-2014-10-604785 |
| format | Article |
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•Significant HLA locus mismatches responsible for transplant-related events were determined in 7898 unrelated marrow donor transplants.•This information provides a rationale for use of an algorithm for unrelated donor selection.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2014-10-604785</identifier><identifier>PMID: 25519752</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Alleles ; Bone Marrow Transplantation - adverse effects ; Bone Marrow Transplantation - statistics & numerical data ; Child ; Child, Preschool ; Female ; Genetic Loci - immunology ; Graft vs Host Disease - epidemiology ; Graft vs Host Disease - genetics ; Graft vs Host Disease - immunology ; Histocompatibility - physiology ; Histocompatibility Testing ; HLA-A Antigens - genetics ; HLA-A Antigens - immunology ; HLA-B Antigens - genetics ; HLA-B Antigens - immunology ; HLA-C Antigens - genetics ; HLA-C Antigens - immunology ; HLA-DP beta-Chains - genetics ; HLA-DP beta-Chains - immunology ; HLA-DQ beta-Chains - genetics ; HLA-DQ beta-Chains - immunology ; HLA-DRB1 Chains - genetics ; HLA-DRB1 Chains - immunology ; Humans ; Infant ; Infant, Newborn ; Leukemia - epidemiology ; Leukemia - genetics ; Leukemia - immunology ; Leukemia - therapy ; Male ; Middle Aged ; Transplantation ; Unrelated Donors ; Young Adult</subject><ispartof>Blood, 2015-02, Vol.125 (7), p.1189-1197</ispartof><rights>2015 American Society of Hematology</rights><rights>2015 by The American Society of Hematology.</rights><rights>2015 by The American Society of Hematology 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-572060d1eb984ab8f16c287c688e34d772de6359258d8aa7e691938ec56feaca3</citedby><cites>FETCH-LOGICAL-c529t-572060d1eb984ab8f16c287c688e34d772de6359258d8aa7e691938ec56feaca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25519752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morishima, Yasuo</creatorcontrib><creatorcontrib>Kashiwase, Koichi</creatorcontrib><creatorcontrib>Matsuo, Keitaro</creatorcontrib><creatorcontrib>Azuma, Fumihiro</creatorcontrib><creatorcontrib>Morishima, Satoko</creatorcontrib><creatorcontrib>Onizuka, Makoto</creatorcontrib><creatorcontrib>Yabe, Toshio</creatorcontrib><creatorcontrib>Murata, Makoto</creatorcontrib><creatorcontrib>Doki, Noriko</creatorcontrib><creatorcontrib>Eto, Tetsuya</creatorcontrib><creatorcontrib>Mori, Takehiko</creatorcontrib><creatorcontrib>Miyamura, Koichi</creatorcontrib><creatorcontrib>Sao, Hiroshi</creatorcontrib><creatorcontrib>Ichinohe, Tatsuo</creatorcontrib><creatorcontrib>Saji, Hiroo</creatorcontrib><creatorcontrib>Kato, Shunichi</creatorcontrib><creatorcontrib>Atsuta, Yoshiko</creatorcontrib><creatorcontrib>Kawa, Keisei</creatorcontrib><creatorcontrib>Kodera, Yoshihisa</creatorcontrib><creatorcontrib>Sasazuki, Takehiko</creatorcontrib><creatorcontrib>Japan Marrow Donor Program</creatorcontrib><title>Biological significance of HLA locus matching in unrelated donor bone marrow transplantation</title><title>Blood</title><addtitle>Blood</addtitle><description>We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell–replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.
•Significant HLA locus mismatches responsible for transplant-related events were determined in 7898 unrelated marrow donor transplants.•This information provides a rationale for use of an algorithm for unrelated donor selection.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Alleles</subject><subject>Bone Marrow Transplantation - adverse effects</subject><subject>Bone Marrow Transplantation - statistics & numerical data</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Genetic Loci - immunology</subject><subject>Graft vs Host Disease - epidemiology</subject><subject>Graft vs Host Disease - genetics</subject><subject>Graft vs Host Disease - immunology</subject><subject>Histocompatibility - physiology</subject><subject>Histocompatibility Testing</subject><subject>HLA-A Antigens - genetics</subject><subject>HLA-A Antigens - immunology</subject><subject>HLA-B Antigens - genetics</subject><subject>HLA-B Antigens - immunology</subject><subject>HLA-C Antigens - genetics</subject><subject>HLA-C Antigens - immunology</subject><subject>HLA-DP beta-Chains - genetics</subject><subject>HLA-DP beta-Chains - immunology</subject><subject>HLA-DQ beta-Chains - genetics</subject><subject>HLA-DQ beta-Chains - immunology</subject><subject>HLA-DRB1 Chains - genetics</subject><subject>HLA-DRB1 Chains - immunology</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Leukemia - epidemiology</subject><subject>Leukemia - genetics</subject><subject>Leukemia - immunology</subject><subject>Leukemia - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Transplantation</subject><subject>Unrelated Donors</subject><subject>Young Adult</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-PFCEQxYnRuOPqNzCGo5dWoJs_fTFZN-qaTOJFbyaEhupZDEON0L0bv72Ms6568QSBV69e1Y-Q55y94tyI11NCDJ1gfOg46xQbtJEPyIZLYTrGBHtINowx1Q2j5mfkSa3fWNP2Qj4mZ0JKPmopNuTr24gJd9G7RGvc5Ti3a_ZAcaZX2wua0K-V7t3ir2Pe0Zjpmgskt0CgATMWOmGGJigFb-lSXK6H5PLiloj5KXk0u1Th2d15Tr68f_f58qrbfvrw8fJi23kpxqWTWjDFAodpNIObzMyVF0Z7ZQz0Q9BaBFC9HIU0wTinQY187A14qWZw3vXn5M3J97BOewgecguS7KHEluuHRRftvz85Xtsd3ti2DqW1agYv7wwKfl-hLnYfq4fUJgFcq-VKSiEVF6JJh5PUF6y1wHzfhjN7BGN_gbFHMMenE5hW9uLviPdFv0n8mQHaom4iFFt9hEYixAJ-sQHj_zv8BEnqoaA</recordid><startdate>20150212</startdate><enddate>20150212</enddate><creator>Morishima, Yasuo</creator><creator>Kashiwase, Koichi</creator><creator>Matsuo, Keitaro</creator><creator>Azuma, Fumihiro</creator><creator>Morishima, Satoko</creator><creator>Onizuka, Makoto</creator><creator>Yabe, Toshio</creator><creator>Murata, Makoto</creator><creator>Doki, Noriko</creator><creator>Eto, Tetsuya</creator><creator>Mori, Takehiko</creator><creator>Miyamura, Koichi</creator><creator>Sao, Hiroshi</creator><creator>Ichinohe, Tatsuo</creator><creator>Saji, Hiroo</creator><creator>Kato, Shunichi</creator><creator>Atsuta, Yoshiko</creator><creator>Kawa, Keisei</creator><creator>Kodera, Yoshihisa</creator><creator>Sasazuki, Takehiko</creator><general>Elsevier Inc</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150212</creationdate><title>Biological significance of HLA locus matching in unrelated donor bone marrow transplantation</title><author>Morishima, Yasuo ; Kashiwase, Koichi ; Matsuo, Keitaro ; Azuma, Fumihiro ; Morishima, Satoko ; Onizuka, Makoto ; Yabe, Toshio ; Murata, Makoto ; Doki, Noriko ; Eto, Tetsuya ; Mori, Takehiko ; Miyamura, Koichi ; Sao, Hiroshi ; Ichinohe, Tatsuo ; Saji, Hiroo ; Kato, Shunichi ; Atsuta, Yoshiko ; Kawa, Keisei ; Kodera, Yoshihisa ; Sasazuki, Takehiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-572060d1eb984ab8f16c287c688e34d772de6359258d8aa7e691938ec56feaca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Alleles</topic><topic>Bone Marrow Transplantation - adverse effects</topic><topic>Bone Marrow Transplantation - statistics & numerical data</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Genetic Loci - immunology</topic><topic>Graft vs Host Disease - epidemiology</topic><topic>Graft vs Host Disease - genetics</topic><topic>Graft vs Host Disease - immunology</topic><topic>Histocompatibility - physiology</topic><topic>Histocompatibility Testing</topic><topic>HLA-A Antigens - genetics</topic><topic>HLA-A Antigens - immunology</topic><topic>HLA-B Antigens - genetics</topic><topic>HLA-B Antigens - immunology</topic><topic>HLA-C Antigens - genetics</topic><topic>HLA-C Antigens - immunology</topic><topic>HLA-DP beta-Chains - genetics</topic><topic>HLA-DP beta-Chains - immunology</topic><topic>HLA-DQ beta-Chains - genetics</topic><topic>HLA-DQ beta-Chains - immunology</topic><topic>HLA-DRB1 Chains - genetics</topic><topic>HLA-DRB1 Chains - immunology</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Leukemia - epidemiology</topic><topic>Leukemia - genetics</topic><topic>Leukemia - immunology</topic><topic>Leukemia - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Transplantation</topic><topic>Unrelated Donors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morishima, Yasuo</creatorcontrib><creatorcontrib>Kashiwase, Koichi</creatorcontrib><creatorcontrib>Matsuo, Keitaro</creatorcontrib><creatorcontrib>Azuma, Fumihiro</creatorcontrib><creatorcontrib>Morishima, Satoko</creatorcontrib><creatorcontrib>Onizuka, Makoto</creatorcontrib><creatorcontrib>Yabe, Toshio</creatorcontrib><creatorcontrib>Murata, Makoto</creatorcontrib><creatorcontrib>Doki, Noriko</creatorcontrib><creatorcontrib>Eto, Tetsuya</creatorcontrib><creatorcontrib>Mori, Takehiko</creatorcontrib><creatorcontrib>Miyamura, Koichi</creatorcontrib><creatorcontrib>Sao, Hiroshi</creatorcontrib><creatorcontrib>Ichinohe, Tatsuo</creatorcontrib><creatorcontrib>Saji, Hiroo</creatorcontrib><creatorcontrib>Kato, Shunichi</creatorcontrib><creatorcontrib>Atsuta, Yoshiko</creatorcontrib><creatorcontrib>Kawa, Keisei</creatorcontrib><creatorcontrib>Kodera, Yoshihisa</creatorcontrib><creatorcontrib>Sasazuki, Takehiko</creatorcontrib><creatorcontrib>Japan Marrow Donor Program</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morishima, Yasuo</au><au>Kashiwase, Koichi</au><au>Matsuo, Keitaro</au><au>Azuma, Fumihiro</au><au>Morishima, Satoko</au><au>Onizuka, Makoto</au><au>Yabe, Toshio</au><au>Murata, Makoto</au><au>Doki, Noriko</au><au>Eto, Tetsuya</au><au>Mori, Takehiko</au><au>Miyamura, Koichi</au><au>Sao, Hiroshi</au><au>Ichinohe, Tatsuo</au><au>Saji, Hiroo</au><au>Kato, Shunichi</au><au>Atsuta, Yoshiko</au><au>Kawa, Keisei</au><au>Kodera, Yoshihisa</au><au>Sasazuki, Takehiko</au><aucorp>Japan Marrow Donor Program</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biological significance of HLA locus matching in unrelated donor bone marrow transplantation</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2015-02-12</date><risdate>2015</risdate><volume>125</volume><issue>7</issue><spage>1189</spage><epage>1197</epage><pages>1189-1197</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell–replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.
•Significant HLA locus mismatches responsible for transplant-related events were determined in 7898 unrelated marrow donor transplants.•This information provides a rationale for use of an algorithm for unrelated donor selection.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25519752</pmid><doi>10.1182/blood-2014-10-604785</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Blood, 2015-02, Vol.125 (7), p.1189-1197 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4326776 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Alleles Bone Marrow Transplantation - adverse effects Bone Marrow Transplantation - statistics & numerical data Child Child, Preschool Female Genetic Loci - immunology Graft vs Host Disease - epidemiology Graft vs Host Disease - genetics Graft vs Host Disease - immunology Histocompatibility - physiology Histocompatibility Testing HLA-A Antigens - genetics HLA-A Antigens - immunology HLA-B Antigens - genetics HLA-B Antigens - immunology HLA-C Antigens - genetics HLA-C Antigens - immunology HLA-DP beta-Chains - genetics HLA-DP beta-Chains - immunology HLA-DQ beta-Chains - genetics HLA-DQ beta-Chains - immunology HLA-DRB1 Chains - genetics HLA-DRB1 Chains - immunology Humans Infant Infant, Newborn Leukemia - epidemiology Leukemia - genetics Leukemia - immunology Leukemia - therapy Male Middle Aged Transplantation Unrelated Donors Young Adult |
| title | Biological significance of HLA locus matching in unrelated donor bone marrow transplantation |
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