Long‐Term Results in Recipients of Combined HLA‐Mismatched Kidney and Bone Marrow Transplantation Without Maintenance Immunosuppression
We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin...
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| Veröffentlicht in: | American journal of transplantation 2014-07, Vol.14 (7), p.1599-1611 |
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| creator | Kawai, T. Sachs, D. H. Sprangers, B. Spitzer, T. R. Saidman, S. L. Zorn, E. Tolkoff‐Rubin, N. Preffer, F. Crisalli, K. Gao, B. Wong, W. Morris, H. LoCascio, S. A. Sayre, P. Shonts, B. Williams, W. W. Smith, R.‐N. Colvin, R. B. Sykes, M. Cosimi, A. B. |
| description | We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4.5–11.4 years, while three required reinstitution of IS after 5–8 years due to recurrence of original disease or chronic antibody‐mediated rejection. Of the 10 renal allografts, three failed due to thrombotic microangiopathy or rejection. When compared with 21 immunologically similar living donor kidney recipients treated with conventional IS, the long‐term IS‐free survivors developed significantly fewer posttransplant complications. Although most recipients treated with none or two doses of rituximab developed donor‐specific antibody (DSA), no DSA was detected in recipients treated with four doses of rituximab. Although further revisions of the current conditioning regimen are planned in order to improve consistency of the results, this study shows that long‐term stable kidney allograft survival without maintenance IS can be achieved following transient mixed chimerism induction.
The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression. |
| doi_str_mv | 10.1111/ajt.12731 |
| format | Article |
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The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.12731</identifier><identifier>PMID: 24903438</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley</publisher><subject>Adult ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Biological and medical sciences ; Bone marrow ; Bone Marrow Transplantation ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Chimerism ; Female ; Follow-Up Studies ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Graft Survival - immunology ; Humans ; immunobiology ; Immunosuppression Therapy ; Immunosuppressive Agents - therapeutic use ; Isoantibodies - blood ; Kidney Diseases - immunology ; Kidney Diseases - surgery ; Kidney Transplantation ; living donors ; Male ; Medical sciences ; Middle Aged ; Postoperative Complications ; Prognosis ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the urinary system ; Tissue, organ and graft immunology ; tolerance ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Transplantation Chimera ; Transplantation Conditioning ; Transplantation Tolerance - immunology ; Transplantation, Homologous ; Transplants & implants ; Young Adult</subject><ispartof>American journal of transplantation, 2014-07, Vol.14 (7), p.1599-1611</ispartof><rights>Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><rights>Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5721-527b9a4bab35aa5ea40ff4ab40e9a2ec784de225e9f4f11cfa8f95b06784f82c3</citedby><cites>FETCH-LOGICAL-c5721-527b9a4bab35aa5ea40ff4ab40e9a2ec784de225e9f4f11cfa8f95b06784f82c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.12731$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.12731$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28609257$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24903438$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawai, T.</creatorcontrib><creatorcontrib>Sachs, D. H.</creatorcontrib><creatorcontrib>Sprangers, B.</creatorcontrib><creatorcontrib>Spitzer, T. R.</creatorcontrib><creatorcontrib>Saidman, S. L.</creatorcontrib><creatorcontrib>Zorn, E.</creatorcontrib><creatorcontrib>Tolkoff‐Rubin, N.</creatorcontrib><creatorcontrib>Preffer, F.</creatorcontrib><creatorcontrib>Crisalli, K.</creatorcontrib><creatorcontrib>Gao, B.</creatorcontrib><creatorcontrib>Wong, W.</creatorcontrib><creatorcontrib>Morris, H.</creatorcontrib><creatorcontrib>LoCascio, S. A.</creatorcontrib><creatorcontrib>Sayre, P.</creatorcontrib><creatorcontrib>Shonts, B.</creatorcontrib><creatorcontrib>Williams, W. W.</creatorcontrib><creatorcontrib>Smith, R.‐N.</creatorcontrib><creatorcontrib>Colvin, R. B.</creatorcontrib><creatorcontrib>Sykes, M.</creatorcontrib><creatorcontrib>Cosimi, A. B.</creatorcontrib><title>Long‐Term Results in Recipients of Combined HLA‐Mismatched Kidney and Bone Marrow Transplantation Without Maintenance Immunosuppression</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4.5–11.4 years, while three required reinstitution of IS after 5–8 years due to recurrence of original disease or chronic antibody‐mediated rejection. Of the 10 renal allografts, three failed due to thrombotic microangiopathy or rejection. When compared with 21 immunologically similar living donor kidney recipients treated with conventional IS, the long‐term IS‐free survivors developed significantly fewer posttransplant complications. Although most recipients treated with none or two doses of rituximab developed donor‐specific antibody (DSA), no DSA was detected in recipients treated with four doses of rituximab. Although further revisions of the current conditioning regimen are planned in order to improve consistency of the results, this study shows that long‐term stable kidney allograft survival without maintenance IS can be achieved following transient mixed chimerism induction.
The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression.</description><subject>Adult</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Bone Marrow Transplantation</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Chimerism</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Graft Survival - immunology</subject><subject>Humans</subject><subject>immunobiology</subject><subject>Immunosuppression Therapy</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Isoantibodies - blood</subject><subject>Kidney Diseases - immunology</subject><subject>Kidney Diseases - surgery</subject><subject>Kidney Transplantation</subject><subject>living donors</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Postoperative Complications</subject><subject>Prognosis</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>Tissue, organ and graft immunology</subject><subject>tolerance</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Transplantation Chimera</subject><subject>Transplantation Conditioning</subject><subject>Transplantation Tolerance - immunology</subject><subject>Transplantation, Homologous</subject><subject>Transplants & implants</subject><subject>Young Adult</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks-O0zAQxiMEYpeFAy-ALCEkOHTXduwmuaxUKmAXukJCRRytiTPeukrsYCeseuPOhWfkSXBpKX8kJHzx2PPT93k8k2UPGT1laZ3BejhlvMjZreyYTSmdTJnIbx_iXB5l92JcU8oKXvK72REXFc1FXh5nXxbeXX_7_HWJoSPvMI7tEIl1KdS2t-jSyRsy911tHTbkYjFL8JWNHQx6lS7e2MbhhoBryHPvkFxBCP6GLAO42LfgBhisd-SDHVZ-HFLaugEdOI3ksutG5-PY9wFjTNT97I6BNuKD_X6SvX_5Yjm_mCzevrqczxYTLQvOJpIXdQWihjqXABJBUGME1IJiBRx1UYoGOZdYGWEY0wZKU8maTlPClFznJ9n5Trcf6w4bnaoM0Ko-2A7CRnmw6s-Msyt17T8pwXlZSZ4Enu4Fgv84YhxUZ6PGNtWLfoyKScmmvOBU_AeaVwWtaEET-vgvdO3H4NJPbAVzVsiy3Ho_21E6-BgDmsO7GVXbaVBpGtSPaUjso98LPZA_25-AJ3sAoobWpK5pG39x5ZRWXBaJO9txN7bFzb8d1ez1cmf9HZTv0Do</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Kawai, T.</creator><creator>Sachs, D. H.</creator><creator>Sprangers, B.</creator><creator>Spitzer, T. R.</creator><creator>Saidman, S. L.</creator><creator>Zorn, E.</creator><creator>Tolkoff‐Rubin, N.</creator><creator>Preffer, F.</creator><creator>Crisalli, K.</creator><creator>Gao, B.</creator><creator>Wong, W.</creator><creator>Morris, H.</creator><creator>LoCascio, S. A.</creator><creator>Sayre, P.</creator><creator>Shonts, B.</creator><creator>Williams, W. W.</creator><creator>Smith, R.‐N.</creator><creator>Colvin, R. B.</creator><creator>Sykes, M.</creator><creator>Cosimi, A. 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Psychology</topic><topic>Fundamental immunology</topic><topic>Graft Survival - immunology</topic><topic>Humans</topic><topic>immunobiology</topic><topic>Immunosuppression Therapy</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Isoantibodies - blood</topic><topic>Kidney Diseases - immunology</topic><topic>Kidney Diseases - surgery</topic><topic>Kidney Transplantation</topic><topic>living donors</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Postoperative Complications</topic><topic>Prognosis</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>Tissue, organ and graft immunology</topic><topic>tolerance</topic><topic>Transfusions. Complications. Transfusion reactions. 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L.</au><au>Zorn, E.</au><au>Tolkoff‐Rubin, N.</au><au>Preffer, F.</au><au>Crisalli, K.</au><au>Gao, B.</au><au>Wong, W.</au><au>Morris, H.</au><au>LoCascio, S. A.</au><au>Sayre, P.</au><au>Shonts, B.</au><au>Williams, W. W.</au><au>Smith, R.‐N.</au><au>Colvin, R. B.</au><au>Sykes, M.</au><au>Cosimi, A. B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long‐Term Results in Recipients of Combined HLA‐Mismatched Kidney and Bone Marrow Transplantation Without Maintenance Immunosuppression</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2014-07</date><risdate>2014</risdate><volume>14</volume><issue>7</issue><spage>1599</spage><epage>1611</epage><pages>1599-1611</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4.5–11.4 years, while three required reinstitution of IS after 5–8 years due to recurrence of original disease or chronic antibody‐mediated rejection. Of the 10 renal allografts, three failed due to thrombotic microangiopathy or rejection. When compared with 21 immunologically similar living donor kidney recipients treated with conventional IS, the long‐term IS‐free survivors developed significantly fewer posttransplant complications. Although most recipients treated with none or two doses of rituximab developed donor‐specific antibody (DSA), no DSA was detected in recipients treated with four doses of rituximab. Although further revisions of the current conditioning regimen are planned in order to improve consistency of the results, this study shows that long‐term stable kidney allograft survival without maintenance IS can be achieved following transient mixed chimerism induction.
The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression.</abstract><cop>Hoboken, NJ</cop><pub>Wiley</pub><pmid>24903438</pmid><doi>10.1111/ajt.12731</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of transplantation, 2014-07, Vol.14 (7), p.1599-1611 |
| issn | 1600-6135 1600-6143 |
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| subjects | Adult Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences Bone marrow Bone Marrow Transplantation Bone marrow, stem cells transplantation. Graft versus host reaction Chimerism Female Follow-Up Studies Fundamental and applied biological sciences. Psychology Fundamental immunology Graft Survival - immunology Humans immunobiology Immunosuppression Therapy Immunosuppressive Agents - therapeutic use Isoantibodies - blood Kidney Diseases - immunology Kidney Diseases - surgery Kidney Transplantation living donors Male Medical sciences Middle Aged Postoperative Complications Prognosis Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system Tissue, organ and graft immunology tolerance Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation Chimera Transplantation Conditioning Transplantation Tolerance - immunology Transplantation, Homologous Transplants & implants Young Adult |
| title | Long‐Term Results in Recipients of Combined HLA‐Mismatched Kidney and Bone Marrow Transplantation Without Maintenance Immunosuppression |
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