Prolonged allogeneic marrow engraftment following nonmyeloablative conditioning using 100 cGy total body irradiation and pentostatin before and pharmacological immunosuppression after transplantation
In a canine model of dog leukocyte antigen (DLA)-identical nonmyeloablative marrow transplantation including postgrafting immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF), engraftment was only transient with 100 cGy total body irradiation (TBI) conditioning, indicating subop...
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| Veröffentlicht in: | Transplantation 2005-11, Vol.80 (10), p.1518-1521 |
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| creator | PANSE, Jens P STORB, Rainer STORER, Barry SANTOS, Erlinda B WENTZEL, Collette SANDMAIER, Brenda M |
| description | In a canine model of dog leukocyte antigen (DLA)-identical nonmyeloablative marrow transplantation including postgrafting immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF), engraftment was only transient with 100 cGy total body irradiation (TBI) conditioning, indicating suboptimal pretransplant immunosuppression. In contrast, grafts after 200 cGy TBI were durable in 11/12 recipients. We hypothesized that addition of pentostatin before transplantation could, in part, substitute for 100 cGy TBI. Pharmacokinetic studies showed pentostatin significantly inhibited adenosine deaminase in canine lymphocytes. Eight dogs were conditioned with 6x4 mg/m pentostatin and 100 cGy TBI, whereas two dogs received 3x4 mg/m pentostatin plus 100 cGy TBI. All were given MMF/CSP posttransplant. All showed initial engraftment; four remained stable mixed chimeras for >32 weeks. The median duration of engraftment was 13 (range 9 to >39) weeks, which was significantly longer than in six historical controls conditioned with 100 cGy TBI alone (median 10, range 3-12 weeks) (P=0.01). |
| doi_str_mv | 10.1097/01.tp.0000181168.42461.0b |
| format | Article |
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In contrast, grafts after 200 cGy TBI were durable in 11/12 recipients. We hypothesized that addition of pentostatin before transplantation could, in part, substitute for 100 cGy TBI. Pharmacokinetic studies showed pentostatin significantly inhibited adenosine deaminase in canine lymphocytes. Eight dogs were conditioned with 6x4 mg/m pentostatin and 100 cGy TBI, whereas two dogs received 3x4 mg/m pentostatin plus 100 cGy TBI. All were given MMF/CSP posttransplant. All showed initial engraftment; four remained stable mixed chimeras for >32 weeks. The median duration of engraftment was 13 (range 9 to >39) weeks, which was significantly longer than in six historical controls conditioned with 100 cGy TBI alone (median 10, range 3-12 weeks) (P=0.01).</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/01.tp.0000181168.42461.0b</identifier><identifier>PMID: 16340800</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Adenosine Deaminase Inhibitors ; Animals ; Biological and medical sciences ; Bone Marrow Transplantation - methods ; Cyclosporine - therapeutic use ; Dogs ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Graft Survival - drug effects ; Graft Survival - physiology ; Graft Survival - radiation effects ; Immunosuppressive Agents - therapeutic use ; Lymphopenia - chemically induced ; Medical sciences ; Mycophenolic Acid - analogs & derivatives ; Mycophenolic Acid - therapeutic use ; Pentostatin - therapeutic use ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tissue, organ and graft immunology ; Transplantation Chimera - immunology ; Transplantation Conditioning - methods ; Transplantation, Homologous ; Whole-Body Irradiation</subject><ispartof>Transplantation, 2005-11, Vol.80 (10), p.1518-1521</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-9364758b64f99229701d95bd3c3c467d3991271316593ce1bf4899e4f5ed48973</citedby><cites>FETCH-LOGICAL-c427t-9364758b64f99229701d95bd3c3c467d3991271316593ce1bf4899e4f5ed48973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17352926$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16340800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PANSE, Jens P</creatorcontrib><creatorcontrib>STORB, Rainer</creatorcontrib><creatorcontrib>STORER, Barry</creatorcontrib><creatorcontrib>SANTOS, Erlinda B</creatorcontrib><creatorcontrib>WENTZEL, Collette</creatorcontrib><creatorcontrib>SANDMAIER, Brenda M</creatorcontrib><title>Prolonged allogeneic marrow engraftment following nonmyeloablative conditioning using 100 cGy total body irradiation and pentostatin before and pharmacological immunosuppression after transplantation</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>In a canine model of dog leukocyte antigen (DLA)-identical nonmyeloablative marrow transplantation including postgrafting immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF), engraftment was only transient with 100 cGy total body irradiation (TBI) conditioning, indicating suboptimal pretransplant immunosuppression. In contrast, grafts after 200 cGy TBI were durable in 11/12 recipients. We hypothesized that addition of pentostatin before transplantation could, in part, substitute for 100 cGy TBI. Pharmacokinetic studies showed pentostatin significantly inhibited adenosine deaminase in canine lymphocytes. Eight dogs were conditioned with 6x4 mg/m pentostatin and 100 cGy TBI, whereas two dogs received 3x4 mg/m pentostatin plus 100 cGy TBI. All were given MMF/CSP posttransplant. All showed initial engraftment; four remained stable mixed chimeras for >32 weeks. The median duration of engraftment was 13 (range 9 to >39) weeks, which was significantly longer than in six historical controls conditioned with 100 cGy TBI alone (median 10, range 3-12 weeks) (P=0.01).</description><subject>Adenosine Deaminase Inhibitors</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Transplantation - methods</subject><subject>Cyclosporine - therapeutic use</subject><subject>Dogs</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Graft Survival - drug effects</subject><subject>Graft Survival - physiology</subject><subject>Graft Survival - radiation effects</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Lymphopenia - chemically induced</subject><subject>Medical sciences</subject><subject>Mycophenolic Acid - analogs & derivatives</subject><subject>Mycophenolic Acid - therapeutic use</subject><subject>Pentostatin - therapeutic use</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tissue, organ and graft immunology</subject><subject>Transplantation Chimera - immunology</subject><subject>Transplantation Conditioning - methods</subject><subject>Transplantation, Homologous</subject><subject>Whole-Body Irradiation</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc-OFCEQxonRuOPqKxg86K1baGgYjmazriab6EHPhIbqFtMNLdBu5gl9LZk_yXCAStXvKyr1IfSOkpYSJT8S2pa1JfXQPaVi3_KOC9qS4Rna0Z7xRpA9eY52hHDaUMbkDXqV8-_K90zKl-iGCsYrQnbo3_cU5xgmcNjMc5wggLd4MSnFJwxhSmYsC4SCx1jLTz5MOMSwHGCOZphN8X8B2xicLz6GY3XLx5sSgu3DAZdYzIyH6A7Yp2ScN0cOm-DwWrvGXGoi4AHGmOCc_mXSYmwdavK2av2ybCHmbV0T5HwSjwUSLsmEvM4mlFPL1-jFaOYMby7vLfr5-f7H3Zfm8dvD17tPj43lnSyNYoLLfj8IPirVdUoS6lQ_OGaZ5UI6phTtJGVU9IpZoMPI90oBH3twNZLsFn04911T_LNBLnrx2cJcB4G4ZU1ldUL0ooLqDNoUc04w6jX5uteDpkQfXdSE6rLqq4v65KImQ9W-vXyyDQu4q_JiWwXeXwCT65LGugvr85WTrO9UJ9h_oeesmA</recordid><startdate>20051127</startdate><enddate>20051127</enddate><creator>PANSE, Jens P</creator><creator>STORB, Rainer</creator><creator>STORER, Barry</creator><creator>SANTOS, Erlinda B</creator><creator>WENTZEL, Collette</creator><creator>SANDMAIER, Brenda M</creator><general>Lippincott</general><scope>IQODW</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>7T5</scope><scope>H94</scope></search><sort><creationdate>20051127</creationdate><title>Prolonged allogeneic marrow engraftment following nonmyeloablative conditioning using 100 cGy total body irradiation and pentostatin before and pharmacological immunosuppression after transplantation</title><author>PANSE, Jens P ; STORB, Rainer ; STORER, Barry ; SANTOS, Erlinda B ; WENTZEL, Collette ; SANDMAIER, Brenda M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-9364758b64f99229701d95bd3c3c467d3991271316593ce1bf4899e4f5ed48973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenosine Deaminase Inhibitors</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Transplantation - methods</topic><topic>Cyclosporine - therapeutic use</topic><topic>Dogs</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Graft Survival - drug effects</topic><topic>Graft Survival - physiology</topic><topic>Graft Survival - radiation effects</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Lymphopenia - chemically induced</topic><topic>Medical sciences</topic><topic>Mycophenolic Acid - analogs & derivatives</topic><topic>Mycophenolic Acid - therapeutic use</topic><topic>Pentostatin - therapeutic use</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tissue, organ and graft immunology</topic><topic>Transplantation Chimera - immunology</topic><topic>Transplantation Conditioning - methods</topic><topic>Transplantation, Homologous</topic><topic>Whole-Body Irradiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PANSE, Jens P</creatorcontrib><creatorcontrib>STORB, Rainer</creatorcontrib><creatorcontrib>STORER, Barry</creatorcontrib><creatorcontrib>SANTOS, Erlinda B</creatorcontrib><creatorcontrib>WENTZEL, Collette</creatorcontrib><creatorcontrib>SANDMAIER, Brenda M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PANSE, Jens P</au><au>STORB, Rainer</au><au>STORER, Barry</au><au>SANTOS, Erlinda B</au><au>WENTZEL, Collette</au><au>SANDMAIER, Brenda M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prolonged allogeneic marrow engraftment following nonmyeloablative conditioning using 100 cGy total body irradiation and pentostatin before and pharmacological immunosuppression after transplantation</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2005-11-27</date><risdate>2005</risdate><volume>80</volume><issue>10</issue><spage>1518</spage><epage>1521</epage><pages>1518-1521</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>In a canine model of dog leukocyte antigen (DLA)-identical nonmyeloablative marrow transplantation including postgrafting immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF), engraftment was only transient with 100 cGy total body irradiation (TBI) conditioning, indicating suboptimal pretransplant immunosuppression. In contrast, grafts after 200 cGy TBI were durable in 11/12 recipients. We hypothesized that addition of pentostatin before transplantation could, in part, substitute for 100 cGy TBI. Pharmacokinetic studies showed pentostatin significantly inhibited adenosine deaminase in canine lymphocytes. Eight dogs were conditioned with 6x4 mg/m pentostatin and 100 cGy TBI, whereas two dogs received 3x4 mg/m pentostatin plus 100 cGy TBI. All were given MMF/CSP posttransplant. All showed initial engraftment; four remained stable mixed chimeras for >32 weeks. The median duration of engraftment was 13 (range 9 to >39) weeks, which was significantly longer than in six historical controls conditioned with 100 cGy TBI alone (median 10, range 3-12 weeks) (P=0.01).</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>16340800</pmid><doi>10.1097/01.tp.0000181168.42461.0b</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine Deaminase Inhibitors Animals Biological and medical sciences Bone Marrow Transplantation - methods Cyclosporine - therapeutic use Dogs Fundamental and applied biological sciences. Psychology Fundamental immunology Graft Survival - drug effects Graft Survival - physiology Graft Survival - radiation effects Immunosuppressive Agents - therapeutic use Lymphopenia - chemically induced Medical sciences Mycophenolic Acid - analogs & derivatives Mycophenolic Acid - therapeutic use Pentostatin - therapeutic use Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tissue, organ and graft immunology Transplantation Chimera - immunology Transplantation Conditioning - methods Transplantation, Homologous Whole-Body Irradiation |
| title | Prolonged allogeneic marrow engraftment following nonmyeloablative conditioning using 100 cGy total body irradiation and pentostatin before and pharmacological immunosuppression after transplantation |
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