Epstein-Barr Virus—Associated Posttransplantation Lymphoproliferative Disorder With Tacrolimus Metabolism Deterioration in Infants After Living-Donor Liver Transplantation
BACKGROUNDPosttransplantation lymphoproliferative disorder (PTLD) in infants after liver transplantation is strongly associated with tacrolimus (Tac) administration and primary Epstein-Barr virus (EBV) transmission. METHODSFrom 1991 to 2012, 32 survivors younger than 2 years who had undergone living...
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| Veröffentlicht in: | Transplantation 2015-01, Vol.99 (1), p.114-119 |
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| creator | Fukushima, Daizo Sato, Kazushige Kawagishi, Naoki Ohuchi, Noriaki Satomi, Susumu |
| description | BACKGROUNDPosttransplantation lymphoproliferative disorder (PTLD) in infants after liver transplantation is strongly associated with tacrolimus (Tac) administration and primary Epstein-Barr virus (EBV) transmission.
METHODSFrom 1991 to 2012, 32 survivors younger than 2 years who had undergone living-donor liver transplantation using Tac for primary immunosuppression were retrospectively investigated for changes in Tac trough levels before and at the onset of posttransplantation viral infection episodes.
RESULTSTwenty-one recipients experienced 33 viral infection episodes associated with EBV-related PTLD (n=5), symptomatic EBV infection without development of PTLD (n=8), and other viral infections (n=20). Although the average Tac trough levels during the 2 months before the onset of viral infection episodes were similar among the 33 episodes (9.0±2.8 ng/mL), the Tac trough levels at the onset were significantly higher in the episodes with PTLD than in those with EBV infection without the development of PTLD and with other viral infections (19.2±9.0 ng/mL vs. 9.3±5.2 ng/mL and 10.6±5.1 ng/mL, respectively) (P |
| doi_str_mv | 10.1097/TP.0000000000000255 |
| format | Article |
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METHODSFrom 1991 to 2012, 32 survivors younger than 2 years who had undergone living-donor liver transplantation using Tac for primary immunosuppression were retrospectively investigated for changes in Tac trough levels before and at the onset of posttransplantation viral infection episodes.
RESULTSTwenty-one recipients experienced 33 viral infection episodes associated with EBV-related PTLD (n=5), symptomatic EBV infection without development of PTLD (n=8), and other viral infections (n=20). Although the average Tac trough levels during the 2 months before the onset of viral infection episodes were similar among the 33 episodes (9.0±2.8 ng/mL), the Tac trough levels at the onset were significantly higher in the episodes with PTLD than in those with EBV infection without the development of PTLD and with other viral infections (19.2±9.0 ng/mL vs. 9.3±5.2 ng/mL and 10.6±5.1 ng/mL, respectively) (P<0.05). Tacrolimus trough levels at the onset of PTLD were significantly higher during the 2 months before the onset (median, 1.83 times higher than average) compared with EBV infection (1.14 times higher) and other viral infections (1.06 times higher) (P<0.05). The Tac blood concentration-to-dose ratio at the onset of PTLD was more than twice as high as the average value during the 2 months before the onset.
CONCLUSIONDeteriorated Tac metabolism accompanied by a positive change in the blood EBV DNA load may enable us to predict the development of PTLD in liver-transplanted infants with viral infection.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/TP.0000000000000255</identifier><identifier>PMID: 24846306</identifier><language>eng</language><publisher>United States: by Lippincott Williams & Wilkins</publisher><subject>Age Factors ; Biomarkers - blood ; DNA, Viral - blood ; Drug Monitoring ; Epstein-Barr virus ; Epstein-Barr Virus Infections - blood ; Epstein-Barr Virus Infections - diagnosis ; Epstein-Barr Virus Infections - virology ; Female ; Herpesvirus 4, Human - genetics ; Humans ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacokinetics ; Infant ; Liver Transplantation - adverse effects ; Living Donors ; Lymphoproliferative Disorders - blood ; Lymphoproliferative Disorders - diagnosis ; Lymphoproliferative Disorders - virology ; Male ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Tacrolimus - blood ; Tacrolimus - pharmacokinetics ; Viral Load</subject><ispartof>Transplantation, 2015-01, Vol.99 (1), p.114-119</ispartof><rights>2015 by Lippincott Williams & Wilkins</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5015-ff29efdfef9f3ae771a211e028df28f9dcf42146ddc14141ba9d96a9d2f6f9d23</citedby><cites>FETCH-LOGICAL-c5015-ff29efdfef9f3ae771a211e028df28f9dcf42146ddc14141ba9d96a9d2f6f9d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24846306$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fukushima, Daizo</creatorcontrib><creatorcontrib>Sato, Kazushige</creatorcontrib><creatorcontrib>Kawagishi, Naoki</creatorcontrib><creatorcontrib>Ohuchi, Noriaki</creatorcontrib><creatorcontrib>Satomi, Susumu</creatorcontrib><title>Epstein-Barr Virus—Associated Posttransplantation Lymphoproliferative Disorder With Tacrolimus Metabolism Deterioration in Infants After Living-Donor Liver Transplantation</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>BACKGROUNDPosttransplantation lymphoproliferative disorder (PTLD) in infants after liver transplantation is strongly associated with tacrolimus (Tac) administration and primary Epstein-Barr virus (EBV) transmission.
METHODSFrom 1991 to 2012, 32 survivors younger than 2 years who had undergone living-donor liver transplantation using Tac for primary immunosuppression were retrospectively investigated for changes in Tac trough levels before and at the onset of posttransplantation viral infection episodes.
RESULTSTwenty-one recipients experienced 33 viral infection episodes associated with EBV-related PTLD (n=5), symptomatic EBV infection without development of PTLD (n=8), and other viral infections (n=20). Although the average Tac trough levels during the 2 months before the onset of viral infection episodes were similar among the 33 episodes (9.0±2.8 ng/mL), the Tac trough levels at the onset were significantly higher in the episodes with PTLD than in those with EBV infection without the development of PTLD and with other viral infections (19.2±9.0 ng/mL vs. 9.3±5.2 ng/mL and 10.6±5.1 ng/mL, respectively) (P<0.05). Tacrolimus trough levels at the onset of PTLD were significantly higher during the 2 months before the onset (median, 1.83 times higher than average) compared with EBV infection (1.14 times higher) and other viral infections (1.06 times higher) (P<0.05). The Tac blood concentration-to-dose ratio at the onset of PTLD was more than twice as high as the average value during the 2 months before the onset.
CONCLUSIONDeteriorated Tac metabolism accompanied by a positive change in the blood EBV DNA load may enable us to predict the development of PTLD in liver-transplanted infants with viral infection.</description><subject>Age Factors</subject><subject>Biomarkers - blood</subject><subject>DNA, Viral - blood</subject><subject>Drug Monitoring</subject><subject>Epstein-Barr virus</subject><subject>Epstein-Barr Virus Infections - blood</subject><subject>Epstein-Barr Virus Infections - diagnosis</subject><subject>Epstein-Barr Virus Infections - virology</subject><subject>Female</subject><subject>Herpesvirus 4, Human - genetics</subject><subject>Humans</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Infant</subject><subject>Liver Transplantation - adverse effects</subject><subject>Living Donors</subject><subject>Lymphoproliferative Disorders - blood</subject><subject>Lymphoproliferative Disorders - diagnosis</subject><subject>Lymphoproliferative Disorders - virology</subject><subject>Male</subject><subject>Predictive Value of Tests</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Tacrolimus - blood</subject><subject>Tacrolimus - pharmacokinetics</subject><subject>Viral Load</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctu1DAUtRAVHQpfgIS8ZJPiRxIny6HTQqWpmEWAZeSJrxlDEgdfp1V3fAS_wU_1S-oyBQELsCU_7jn3XPseQp5xdsxZrV42m2P2-xBF8YAseCHzrGQVe0gWjOU841KqQ_IY8VPiFFKpR-RQ5FVeSlYuyPfTCSO4MXulQ6DvXZjx5uu3JaLvnI5g6MZjjEGPOPV6jDo6P9L19TDt_BR87yyEFLsEunLog4FAP7i4o43u7tBhRnoBUW_TGQe6ggjB-bBXcSM9H20SRbq0CaBrd-nGj9nKj_7HJYWaPys_IQdW9whP7_cj8u7stDl5k63fvj4_Wa6zrmC8yKwVNVhjwdZWalCKa8E5MFEZKypbm87mguelMR3P09zq2tRlWoQtEyrkEXmx101__DIDxnZw2EGfHgJ-xpYrnrpdFoL9n1rKOq9qxlSiyj019QYxgG2n4AYdrlvO2jtL22bT_m1pynp-X2DeDmB-5fz0MBHUnnDl-9RG_NzPVxDaHeg-7v4pfQvFGbOI</recordid><startdate>201501</startdate><enddate>201501</enddate><creator>Fukushima, Daizo</creator><creator>Sato, Kazushige</creator><creator>Kawagishi, Naoki</creator><creator>Ohuchi, Noriaki</creator><creator>Satomi, Susumu</creator><general>by Lippincott Williams & Wilkins</general><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>7T5</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>201501</creationdate><title>Epstein-Barr Virus—Associated Posttransplantation Lymphoproliferative Disorder With Tacrolimus Metabolism Deterioration in Infants After Living-Donor Liver Transplantation</title><author>Fukushima, Daizo ; Sato, Kazushige ; Kawagishi, Naoki ; Ohuchi, Noriaki ; Satomi, Susumu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5015-ff29efdfef9f3ae771a211e028df28f9dcf42146ddc14141ba9d96a9d2f6f9d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Age Factors</topic><topic>Biomarkers - blood</topic><topic>DNA, Viral - blood</topic><topic>Drug Monitoring</topic><topic>Epstein-Barr virus</topic><topic>Epstein-Barr Virus Infections - blood</topic><topic>Epstein-Barr Virus Infections - diagnosis</topic><topic>Epstein-Barr Virus Infections - virology</topic><topic>Female</topic><topic>Herpesvirus 4, Human - genetics</topic><topic>Humans</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Infant</topic><topic>Liver Transplantation - adverse effects</topic><topic>Living Donors</topic><topic>Lymphoproliferative Disorders - blood</topic><topic>Lymphoproliferative Disorders - diagnosis</topic><topic>Lymphoproliferative Disorders - virology</topic><topic>Male</topic><topic>Predictive Value of Tests</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Tacrolimus - blood</topic><topic>Tacrolimus - pharmacokinetics</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fukushima, Daizo</creatorcontrib><creatorcontrib>Sato, Kazushige</creatorcontrib><creatorcontrib>Kawagishi, Naoki</creatorcontrib><creatorcontrib>Ohuchi, Noriaki</creatorcontrib><creatorcontrib>Satomi, Susumu</creatorcontrib><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>Immunology Abstracts</collection><collection>Virology and AIDS 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>Fukushima, Daizo</au><au>Sato, Kazushige</au><au>Kawagishi, Naoki</au><au>Ohuchi, Noriaki</au><au>Satomi, Susumu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epstein-Barr Virus—Associated Posttransplantation Lymphoproliferative Disorder With Tacrolimus Metabolism Deterioration in Infants After Living-Donor Liver Transplantation</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2015-01</date><risdate>2015</risdate><volume>99</volume><issue>1</issue><spage>114</spage><epage>119</epage><pages>114-119</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><abstract>BACKGROUNDPosttransplantation lymphoproliferative disorder (PTLD) in infants after liver transplantation is strongly associated with tacrolimus (Tac) administration and primary Epstein-Barr virus (EBV) transmission.
METHODSFrom 1991 to 2012, 32 survivors younger than 2 years who had undergone living-donor liver transplantation using Tac for primary immunosuppression were retrospectively investigated for changes in Tac trough levels before and at the onset of posttransplantation viral infection episodes.
RESULTSTwenty-one recipients experienced 33 viral infection episodes associated with EBV-related PTLD (n=5), symptomatic EBV infection without development of PTLD (n=8), and other viral infections (n=20). Although the average Tac trough levels during the 2 months before the onset of viral infection episodes were similar among the 33 episodes (9.0±2.8 ng/mL), the Tac trough levels at the onset were significantly higher in the episodes with PTLD than in those with EBV infection without the development of PTLD and with other viral infections (19.2±9.0 ng/mL vs. 9.3±5.2 ng/mL and 10.6±5.1 ng/mL, respectively) (P<0.05). Tacrolimus trough levels at the onset of PTLD were significantly higher during the 2 months before the onset (median, 1.83 times higher than average) compared with EBV infection (1.14 times higher) and other viral infections (1.06 times higher) (P<0.05). The Tac blood concentration-to-dose ratio at the onset of PTLD was more than twice as high as the average value during the 2 months before the onset.
CONCLUSIONDeteriorated Tac metabolism accompanied by a positive change in the blood EBV DNA load may enable us to predict the development of PTLD in liver-transplanted infants with viral infection.</abstract><cop>United States</cop><pub>by Lippincott Williams & Wilkins</pub><pmid>24846306</pmid><doi>10.1097/TP.0000000000000255</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age Factors Biomarkers - blood DNA, Viral - blood Drug Monitoring Epstein-Barr virus Epstein-Barr Virus Infections - blood Epstein-Barr Virus Infections - diagnosis Epstein-Barr Virus Infections - virology Female Herpesvirus 4, Human - genetics Humans Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacokinetics Infant Liver Transplantation - adverse effects Living Donors Lymphoproliferative Disorders - blood Lymphoproliferative Disorders - diagnosis Lymphoproliferative Disorders - virology Male Predictive Value of Tests Retrospective Studies Risk Factors Tacrolimus - blood Tacrolimus - pharmacokinetics Viral Load |
| title | Epstein-Barr Virus—Associated Posttransplantation Lymphoproliferative Disorder With Tacrolimus Metabolism Deterioration in Infants After Living-Donor Liver Transplantation |
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