Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome
•The impact of donor age and sex but not CMV matching is comparable with that of single HLA disparity on survival after HSCT.•Similar survival after matched unrelated and related donor HSCT for AML or MDS reflects lower NRM but higher relapse risks in the latter. Increasing donor–recipient HLA dispa...
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| Veröffentlicht in: | Biology of blood and marrow transplantation 2018-12, Vol.24 (12), p.2558-2567 |
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| creator | Ayuk, Francis Beelen, Dietrich W. Bornhäuser, Martin Stelljes, Matthias Zabelina, Tatjana Finke, Jürgen Kobbe, Guido Wolff, Daniel Wagner, Eva-Maria Christopeit, Maximilian Schmid, Christoph Ottinger, Hellmut Groth, Christoph Faul, Christoph Bertz, Hartmut Rachlis, Elena Wolschke, Christine Schetelig, Johannes Horn, Peter A. Mytilineos, Joannis Guellstorf, Martina Kelsch, Reinhard Fleischhauer, Katharina Kröger, Nicolaus Bethge, Wolfgang |
| description | •The impact of donor age and sex but not CMV matching is comparable with that of single HLA disparity on survival after HSCT.•Similar survival after matched unrelated and related donor HSCT for AML or MDS reflects lower NRM but higher relapse risks in the latter.
Increasing donor–recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated ( |
| doi_str_mv | 10.1016/j.bbmt.2018.06.026 |
| format | Article |
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Increasing donor–recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (<10/10 MMUD, n = 790). Overall survival (OS) was similar after MRD compared with 10/10 MUD HSCT, reflecting opposing hazards of relapse (hazard ratio [HR], 1.32; P < .002) and nonrelapse mortality (HR, .63; P < .001). After UD HSCT, increasing HLA disparity was associated with inferior OS (HR, 1.21 [P < .02] and HR, 1.57 [P < .001] for 9/10 and ≤8/10 MMUD, respectively, compared with 10/10 MUD). Among non-HLA donor characteristics, age, sex mismatching (male recipient–female donor), and cytomegalovirus (CMV) mismatching (positive recipient–negative donor) impacted OS. Multivariate subgroup analysis showed that OS was similar after HSCT from the youngest 9/10 MMUD (<30 years) compared with the oldest 10/10 MUD (>40 years) (HR, 1.18; P = .25) and also in male patients transplanted from female 10/10 MUD compared with male 9/10 MMUD (HR, .89; P = .46). In contrast, OS of CMV-positive patients tended to be better with CMV-negative 10/10 MUDs compared with CMV-positive 9/10 MMUDs (HR, 1.31; P = .04). Because of low patient numbers in subgroups, definite conclusions and establishment of a hierarchy among HLA matching and non-HLA donor characteristics could not be made. Our data suggest that the impact of donor age and sex mismatch but not CMV mismatch on outcome of allogeneic HSCT may be comparable with that of single HLA disparity.]]></description><identifier>ISSN: 1083-8791</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2018.06.026</identifier><identifier>PMID: 29966760</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>HLA disparity ; Non-HLA donor characteristics</subject><ispartof>Biology of blood and marrow transplantation, 2018-12, Vol.24 (12), p.2558-2567</ispartof><rights>2018</rights><rights>Copyright © 2018. Published by Elsevier Inc.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-7aff318998bea56a43d7576a944f94191981b2761c5615246dbf9c065f68b7283</citedby><cites>FETCH-LOGICAL-c466t-7aff318998bea56a43d7576a944f94191981b2761c5615246dbf9c065f68b7283</cites><orcidid>0000-0002-1799-5927</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbmt.2018.06.026$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29966760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ayuk, Francis</creatorcontrib><creatorcontrib>Beelen, Dietrich W.</creatorcontrib><creatorcontrib>Bornhäuser, Martin</creatorcontrib><creatorcontrib>Stelljes, Matthias</creatorcontrib><creatorcontrib>Zabelina, Tatjana</creatorcontrib><creatorcontrib>Finke, Jürgen</creatorcontrib><creatorcontrib>Kobbe, Guido</creatorcontrib><creatorcontrib>Wolff, Daniel</creatorcontrib><creatorcontrib>Wagner, Eva-Maria</creatorcontrib><creatorcontrib>Christopeit, Maximilian</creatorcontrib><creatorcontrib>Schmid, Christoph</creatorcontrib><creatorcontrib>Ottinger, Hellmut</creatorcontrib><creatorcontrib>Groth, Christoph</creatorcontrib><creatorcontrib>Faul, Christoph</creatorcontrib><creatorcontrib>Bertz, Hartmut</creatorcontrib><creatorcontrib>Rachlis, Elena</creatorcontrib><creatorcontrib>Wolschke, Christine</creatorcontrib><creatorcontrib>Schetelig, Johannes</creatorcontrib><creatorcontrib>Horn, Peter A.</creatorcontrib><creatorcontrib>Mytilineos, Joannis</creatorcontrib><creatorcontrib>Guellstorf, Martina</creatorcontrib><creatorcontrib>Kelsch, Reinhard</creatorcontrib><creatorcontrib>Fleischhauer, Katharina</creatorcontrib><creatorcontrib>Kröger, Nicolaus</creatorcontrib><creatorcontrib>Bethge, Wolfgang</creatorcontrib><title>Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome</title><title>Biology of blood and marrow transplantation</title><addtitle>Biol Blood Marrow Transplant</addtitle><description><![CDATA[•The impact of donor age and sex but not CMV matching is comparable with that of single HLA disparity on survival after HSCT.•Similar survival after matched unrelated and related donor HSCT for AML or MDS reflects lower NRM but higher relapse risks in the latter.
Increasing donor–recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (<10/10 MMUD, n = 790). Overall survival (OS) was similar after MRD compared with 10/10 MUD HSCT, reflecting opposing hazards of relapse (hazard ratio [HR], 1.32; P < .002) and nonrelapse mortality (HR, .63; P < .001). After UD HSCT, increasing HLA disparity was associated with inferior OS (HR, 1.21 [P < .02] and HR, 1.57 [P < .001] for 9/10 and ≤8/10 MMUD, respectively, compared with 10/10 MUD). Among non-HLA donor characteristics, age, sex mismatching (male recipient–female donor), and cytomegalovirus (CMV) mismatching (positive recipient–negative donor) impacted OS. Multivariate subgroup analysis showed that OS was similar after HSCT from the youngest 9/10 MMUD (<30 years) compared with the oldest 10/10 MUD (>40 years) (HR, 1.18; P = .25) and also in male patients transplanted from female 10/10 MUD compared with male 9/10 MMUD (HR, .89; P = .46). In contrast, OS of CMV-positive patients tended to be better with CMV-negative 10/10 MUDs compared with CMV-positive 9/10 MMUDs (HR, 1.31; P = .04). Because of low patient numbers in subgroups, definite conclusions and establishment of a hierarchy among HLA matching and non-HLA donor characteristics could not be made. Our data suggest that the impact of donor age and sex mismatch but not CMV mismatch on outcome of allogeneic HSCT may be comparable with that of single HLA disparity.]]></description><subject>HLA disparity</subject><subject>Non-HLA donor characteristics</subject><issn>1083-8791</issn><issn>1523-6536</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kctu1DAUhiMEoqXwAiyQl2wS7FxObInNaKAXadpKbVlbjnPSekjswXYqzUP1Het0CktWto7-i875suwzowWjDL5ti66bYlFSxgsKBS3hTXbMmrLKoangbfpTXuW8Fewo-xDCllLa1ly8z45KIQBaoMfZ0w2OKppHJBfTTulI3EDONytyqaJ-MPaeKNuTK2fzZfjDWefJ-kH5pERvQjQ6EGfJ9Ry1mzAs7tU4unu0aDS5jTiRNY4jufPKht2obExlyTCknJWeI5LLPY7O9GSD82-cjHopfBn2-8WxdJDbve19KviYvRvUGPDT63uS_Tr9ebc-zzfXZxfr1SbXNUDMWzUMFeNC8A5VA6qu-rZpQYm6HkTNBBOcdWULTDeQ7lVD3w1CU2gG4F1b8uok-3rI3Xn3Z8YQ5WSCTosoi24OsqRQtYkBr5O0PEi1dyF4HOTOm0n5vWRULpjkVi6Y5IJJUpAJUzJ9ec2fuwn7f5a_XJLg-0GAactHg14GbdBq7I1HHWXvzP_ynwFLd6U6</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Ayuk, Francis</creator><creator>Beelen, Dietrich W.</creator><creator>Bornhäuser, Martin</creator><creator>Stelljes, Matthias</creator><creator>Zabelina, Tatjana</creator><creator>Finke, Jürgen</creator><creator>Kobbe, Guido</creator><creator>Wolff, Daniel</creator><creator>Wagner, Eva-Maria</creator><creator>Christopeit, Maximilian</creator><creator>Schmid, Christoph</creator><creator>Ottinger, Hellmut</creator><creator>Groth, Christoph</creator><creator>Faul, Christoph</creator><creator>Bertz, Hartmut</creator><creator>Rachlis, Elena</creator><creator>Wolschke, Christine</creator><creator>Schetelig, Johannes</creator><creator>Horn, Peter A.</creator><creator>Mytilineos, Joannis</creator><creator>Guellstorf, Martina</creator><creator>Kelsch, Reinhard</creator><creator>Fleischhauer, Katharina</creator><creator>Kröger, Nicolaus</creator><creator>Bethge, Wolfgang</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1799-5927</orcidid></search><sort><creationdate>201812</creationdate><title>Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome</title><author>Ayuk, Francis ; 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Increasing donor–recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (<10/10 MMUD, n = 790). Overall survival (OS) was similar after MRD compared with 10/10 MUD HSCT, reflecting opposing hazards of relapse (hazard ratio [HR], 1.32; P < .002) and nonrelapse mortality (HR, .63; P < .001). After UD HSCT, increasing HLA disparity was associated with inferior OS (HR, 1.21 [P < .02] and HR, 1.57 [P < .001] for 9/10 and ≤8/10 MMUD, respectively, compared with 10/10 MUD). Among non-HLA donor characteristics, age, sex mismatching (male recipient–female donor), and cytomegalovirus (CMV) mismatching (positive recipient–negative donor) impacted OS. Multivariate subgroup analysis showed that OS was similar after HSCT from the youngest 9/10 MMUD (<30 years) compared with the oldest 10/10 MUD (>40 years) (HR, 1.18; P = .25) and also in male patients transplanted from female 10/10 MUD compared with male 9/10 MMUD (HR, .89; P = .46). In contrast, OS of CMV-positive patients tended to be better with CMV-negative 10/10 MUDs compared with CMV-positive 9/10 MMUDs (HR, 1.31; P = .04). Because of low patient numbers in subgroups, definite conclusions and establishment of a hierarchy among HLA matching and non-HLA donor characteristics could not be made. Our data suggest that the impact of donor age and sex mismatch but not CMV mismatch on outcome of allogeneic HSCT may be comparable with that of single HLA disparity.]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29966760</pmid><doi>10.1016/j.bbmt.2018.06.026</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1799-5927</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Biology of blood and marrow transplantation, 2018-12, Vol.24 (12), p.2558-2567 |
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| source | Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | HLA disparity Non-HLA donor characteristics |
| title | Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome |
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