Influence of Induction Therapy, Immunosuppressive Regimen and Anti-viral Prophylaxis on Development of Lymphomas After Heart Transplantation: Data From the Spanish Post–Heart Transplant Tumour Registry
Background Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods This study was a retrospective review of 3,393 patients...
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| Veröffentlicht in: | The Journal of heart and lung transplantation 2007-11, Vol.26 (11), p.1105-1109 |
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| creator | Crespo-Leiro, Maria G., MD Alonso-Pulpón, Luis, MD Arizón, José M., MD Almenar, Luis, MD Delgado, Juan F., MD Palomo, Jesús, MD Manito, Nicolás, MD Rábago, Gregorio, MD Lage, Ernesto, MD Diaz, Beatriz, MD Roig, Eulalia, MD Pascual, Domingo, MD Blasco, Teresa, MD de la Fuente, Luis, MD Campreciós, Marta, MD Vázquez de Prada, José A., MD Muñiz, Javier, MD |
| description | Background Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively. |
| doi_str_mv | 10.1016/j.healun.2007.08.010 |
| format | Article |
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It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.</description><identifier>ISSN: 1053-2498</identifier><identifier>EISSN: 1557-3117</identifier><identifier>DOI: 10.1016/j.healun.2007.08.010</identifier><identifier>PMID: 18022075</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Acyclovir - therapeutic use ; Adult ; Antilymphocyte Serum - adverse effects ; Antilymphocyte Serum - therapeutic use ; Antiviral Agents - therapeutic use ; Biological and medical sciences ; Female ; Ganciclovir - therapeutic use ; Heart Transplantation - adverse effects ; Hematologic and hematopoietic diseases ; Humans ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - therapeutic use ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymphoma - etiology ; Lymphoma - prevention & control ; Male ; Medical sciences ; Middle Aged ; Multivariate Analysis ; Muromonab-CD3 - adverse effects ; Muromonab-CD3 - therapeutic use ; Registries - statistics & numerical data ; Retrospective Studies ; Risk Factors ; Spain ; Surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart ; Virus Diseases - complications</subject><ispartof>The Journal of heart and lung transplantation, 2007-11, Vol.26 (11), p.1105-1109</ispartof><rights>International Society for Heart and Lung Transplantation</rights><rights>2007 International Society for Heart and Lung Transplantation</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-c5445367af3ec7c8fc39a825a2cb21ab01818db7ccdb752c84d7c620c583f463</citedby><cites>FETCH-LOGICAL-c491t-c5445367af3ec7c8fc39a825a2cb21ab01818db7ccdb752c84d7c620c583f463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.healun.2007.08.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19896404$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18022075$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crespo-Leiro, Maria G., MD</creatorcontrib><creatorcontrib>Alonso-Pulpón, Luis, MD</creatorcontrib><creatorcontrib>Arizón, José M., MD</creatorcontrib><creatorcontrib>Almenar, Luis, MD</creatorcontrib><creatorcontrib>Delgado, Juan F., MD</creatorcontrib><creatorcontrib>Palomo, Jesús, MD</creatorcontrib><creatorcontrib>Manito, Nicolás, MD</creatorcontrib><creatorcontrib>Rábago, Gregorio, MD</creatorcontrib><creatorcontrib>Lage, Ernesto, MD</creatorcontrib><creatorcontrib>Diaz, Beatriz, MD</creatorcontrib><creatorcontrib>Roig, Eulalia, MD</creatorcontrib><creatorcontrib>Pascual, Domingo, MD</creatorcontrib><creatorcontrib>Blasco, Teresa, MD</creatorcontrib><creatorcontrib>de la Fuente, Luis, MD</creatorcontrib><creatorcontrib>Campreciós, Marta, MD</creatorcontrib><creatorcontrib>Vázquez de Prada, José A., MD</creatorcontrib><creatorcontrib>Muñiz, Javier, MD</creatorcontrib><title>Influence of Induction Therapy, Immunosuppressive Regimen and Anti-viral Prophylaxis on Development of Lymphomas After Heart Transplantation: Data From the Spanish Post–Heart Transplant Tumour Registry</title><title>The Journal of heart and lung transplantation</title><addtitle>J Heart Lung Transplant</addtitle><description>Background Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.</description><subject>Acyclovir - therapeutic use</subject><subject>Adult</subject><subject>Antilymphocyte Serum - adverse effects</subject><subject>Antilymphocyte Serum - therapeutic use</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Ganciclovir - therapeutic use</subject><subject>Heart Transplantation - adverse effects</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymphoma - etiology</subject><subject>Lymphoma - prevention & control</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Muromonab-CD3 - adverse effects</subject><subject>Muromonab-CD3 - therapeutic use</subject><subject>Registries - statistics & numerical data</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Spain</subject><subject>Surgery</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><subject>Virus Diseases - complications</subject><issn>1053-2498</issn><issn>1557-3117</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9u1DAQxiMEoqXwBgj5Aiey-E-ceDkgrVpKV6pERffAzfI6E-IlsVPbWZEb78Bj8RY8CQ67UqVeuHh8-M03o--bLHtJ8IJgUr7bLVpQ3WgXFONqgcUCE_woOyWcVzkjpHqc_piznBZLcZI9C2GHMaaM06fZCRGYUlzx0-z32jbdCFYDcg1a23rU0TiLNi14NUxv0brvR-vCOAweQjB7QF_gm-nBImVrtLLR5HvjVYduvBvaqVM_TEBJ4AL20LkhgXFWvp76oXW9CmjVRPDoCpSPaOOVDUOnbFTz1PfoQkWFLr3rUWwB3Q7KmtCiGxfin5-_Hvagzdi70f9bKEQ_Pc-eNKoL8OJYz7LN5cfN-VV-_fnT-nx1netiSWKueVFwVlaqYaArLRrNlkpQrqjeUqK2mAgi6m2ldXo41aKoK11SrLlgTVGys-zNQXbw7m6EEGVvgoYurQRuDLIUnBFesgQWB1B7F4KHRg7e9MpPkmA5Zyh38pChnDOUWMiUYWp7ddQftz3U903H0BLw-giooFXXJEO0CffcUizLAheJ-3DgIJmxN-Bl0GaOujYedJS1M__b5KGA7ow1aeZ3mCDskvk2GS2JDFRieTvf23xuuMK4LKqv7C_RGNd7</recordid><startdate>20071101</startdate><enddate>20071101</enddate><creator>Crespo-Leiro, Maria G., MD</creator><creator>Alonso-Pulpón, Luis, MD</creator><creator>Arizón, José M., MD</creator><creator>Almenar, Luis, MD</creator><creator>Delgado, Juan F., MD</creator><creator>Palomo, Jesús, MD</creator><creator>Manito, Nicolás, MD</creator><creator>Rábago, Gregorio, MD</creator><creator>Lage, Ernesto, MD</creator><creator>Diaz, Beatriz, MD</creator><creator>Roig, Eulalia, MD</creator><creator>Pascual, Domingo, MD</creator><creator>Blasco, Teresa, MD</creator><creator>de la Fuente, Luis, MD</creator><creator>Campreciós, Marta, MD</creator><creator>Vázquez de Prada, José A., MD</creator><creator>Muñiz, Javier, MD</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7X8</scope></search><sort><creationdate>20071101</creationdate><title>Influence of Induction Therapy, Immunosuppressive Regimen and Anti-viral Prophylaxis on Development of Lymphomas After Heart Transplantation: Data From the Spanish Post–Heart Transplant Tumour Registry</title><author>Crespo-Leiro, Maria G., MD ; Alonso-Pulpón, Luis, MD ; Arizón, José M., MD ; Almenar, Luis, MD ; Delgado, Juan F., MD ; Palomo, Jesús, MD ; Manito, Nicolás, MD ; Rábago, Gregorio, MD ; Lage, Ernesto, MD ; Diaz, Beatriz, MD ; Roig, Eulalia, MD ; Pascual, Domingo, MD ; Blasco, Teresa, MD ; de la Fuente, Luis, MD ; Campreciós, Marta, MD ; Vázquez de Prada, José A., MD ; Muñiz, Javier, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-c5445367af3ec7c8fc39a825a2cb21ab01818db7ccdb752c84d7c620c583f463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acyclovir - therapeutic use</topic><topic>Adult</topic><topic>Antilymphocyte Serum - adverse effects</topic><topic>Antilymphocyte Serum - therapeutic use</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Ganciclovir - therapeutic use</topic><topic>Heart Transplantation - adverse effects</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymphoma - etiology</topic><topic>Lymphoma - prevention & control</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Muromonab-CD3 - adverse effects</topic><topic>Muromonab-CD3 - therapeutic use</topic><topic>Registries - statistics & numerical data</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Spain</topic><topic>Surgery</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><topic>Virus Diseases - complications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crespo-Leiro, Maria G., MD</creatorcontrib><creatorcontrib>Alonso-Pulpón, Luis, MD</creatorcontrib><creatorcontrib>Arizón, José M., MD</creatorcontrib><creatorcontrib>Almenar, Luis, MD</creatorcontrib><creatorcontrib>Delgado, Juan F., MD</creatorcontrib><creatorcontrib>Palomo, Jesús, MD</creatorcontrib><creatorcontrib>Manito, Nicolás, MD</creatorcontrib><creatorcontrib>Rábago, Gregorio, MD</creatorcontrib><creatorcontrib>Lage, Ernesto, MD</creatorcontrib><creatorcontrib>Diaz, Beatriz, MD</creatorcontrib><creatorcontrib>Roig, Eulalia, MD</creatorcontrib><creatorcontrib>Pascual, Domingo, MD</creatorcontrib><creatorcontrib>Blasco, Teresa, MD</creatorcontrib><creatorcontrib>de la Fuente, Luis, MD</creatorcontrib><creatorcontrib>Campreciós, Marta, MD</creatorcontrib><creatorcontrib>Vázquez de Prada, José A., MD</creatorcontrib><creatorcontrib>Muñiz, Javier, MD</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>MEDLINE - Academic</collection><jtitle>The Journal of heart and lung transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crespo-Leiro, Maria G., MD</au><au>Alonso-Pulpón, Luis, MD</au><au>Arizón, José M., MD</au><au>Almenar, Luis, MD</au><au>Delgado, Juan F., MD</au><au>Palomo, Jesús, MD</au><au>Manito, Nicolás, MD</au><au>Rábago, Gregorio, MD</au><au>Lage, Ernesto, MD</au><au>Diaz, Beatriz, MD</au><au>Roig, Eulalia, MD</au><au>Pascual, Domingo, MD</au><au>Blasco, Teresa, MD</au><au>de la Fuente, Luis, MD</au><au>Campreciós, Marta, MD</au><au>Vázquez de Prada, José A., MD</au><au>Muñiz, Javier, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of Induction Therapy, Immunosuppressive Regimen and Anti-viral Prophylaxis on Development of Lymphomas After Heart Transplantation: Data From the Spanish Post–Heart Transplant Tumour Registry</atitle><jtitle>The Journal of heart and lung transplantation</jtitle><addtitle>J Heart Lung Transplant</addtitle><date>2007-11-01</date><risdate>2007</risdate><volume>26</volume><issue>11</issue><spage>1105</spage><epage>1109</epage><pages>1105-1109</pages><issn>1053-2498</issn><eissn>1557-3117</eissn><abstract>Background Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18022075</pmid><doi>10.1016/j.healun.2007.08.010</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of heart and lung transplantation, 2007-11, Vol.26 (11), p.1105-1109 |
| issn | 1053-2498 1557-3117 |
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| subjects | Acyclovir - therapeutic use Adult Antilymphocyte Serum - adverse effects Antilymphocyte Serum - therapeutic use Antiviral Agents - therapeutic use Biological and medical sciences Female Ganciclovir - therapeutic use Heart Transplantation - adverse effects Hematologic and hematopoietic diseases Humans Immunosuppressive Agents - adverse effects Immunosuppressive Agents - therapeutic use Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphoma - etiology Lymphoma - prevention & control Male Medical sciences Middle Aged Multivariate Analysis Muromonab-CD3 - adverse effects Muromonab-CD3 - therapeutic use Registries - statistics & numerical data Retrospective Studies Risk Factors Spain Surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart Virus Diseases - complications |
| title | Influence of Induction Therapy, Immunosuppressive Regimen and Anti-viral Prophylaxis on Development of Lymphomas After Heart Transplantation: Data From the Spanish Post–Heart Transplant Tumour Registry |
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