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Use of proliferation signal inhibitors in the management of post-transplant malignancies—clinical guidance

Identifieur interne : 009045 ( Main/Exploration ); précédent : 009044; suivant : 009046

Use of proliferation signal inhibitors in the management of post-transplant malignancies—clinical guidance

Auteurs : Josep M. Campistol [Australie] ; Joan Albanell [Australie] ; Wolfgang Arns [Australie] ; Ioannis Boletis [Australie] ; Jacques Dantal [Australie] ; J. W. De Fijter [Australie] ; Svend Aage Mortensen [Australie] ; Hans-Hellmut Neumayer [Australie] ; Ole Yen [Australie] ; Julio Pascual [Australie] ; Erich Pohanka [Australie] ; F. Paolo Schena [Australie] ; Daniel Ser N [Australie] ; Vito Sparacino [Australie] ; Jeremy R. Chapman [Australie]

Source :

RBID : ISTEX:24383F05F5180AD7BDCFDC71BA61D10504B9C3B4

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English descriptors

Abstract

Increasing success in renal transplantation and longer patient survival has meant that post-transplant malignancies are having an increasing impact on long-term graft and patient survival. Choice of the immunosuppressive agents provides one of the controllable risk factors for the development of malignancies in this population. Calcineurin inhibitors (CNIs) are associated with an increased incidence of cancers, whereas the proliferation signal inhibitors (PSIs), everolimus and sirolimus have demonstrated anti-oncogenic effects in pre-clinical models and are currently being investigated as anti-cancer agents in clinical trials. There is increasing evidence demonstrating a lower incidence of post-transplant malignancies in renal transplant recipients receiving PSI-based immunosuppression compared with those receiving CNIs. Conversion from CNIs to PSIs has been shown to lead to the regression of Kaposi's sarcoma in renal transplant recipients and is now part of accepted standard care for this tumour in this setting. The anti-cancer properties of PSI-based regimens have the potential to combine the dual benefits of immunosuppression without the use of CNIs and the direct anti-oncogenic effects through their inhibition of the mammalian target of rapamycin (mTOR) signalling pathway. In the absence of formal clinical trial evidence on the best way to use PSIs in this setting, a workshop was held to provide practical guidance on immunosuppressive strategies in the context of malignancy, given the current state of knowledge.

Url:
DOI: 10.1093/ndt/gfm090


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<wicri:regionArea>Servei de Nefrologia I Transplantament Renal, Renal Transplant Unit, Hospital Clinic, Universitat de Barcelona, 170, Villarroel, Jefe de Servico, Servico de Oncología Médica, Hospital del Mar-IMAS, Paseo Maritimo 25-29, Barcelona 08003, Spain, Cologne General Hospital, Merheim Medical Centre, Koeln-Merheim, Germany, Department of Nephrology and Transplantation, Laiko Hospital, Athens, Greece, ITERT, Department of Nephrology and Clinical Immunology, 30 Bd Jean Monnet, CHU Nantes, 44093 Nantes, Cedex 01, France, Department of Nephrology, Leiden University Medical Center, NL-2333ZA Leiden, The Netherlands, Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, University Clinic Charité, Campus Charité Mitte, Department of Nephrology, Berlin, Germany, Surgical Department, Rikshospitalet University Hospital, Oslo, Norway, Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Spain, Division of Nephrology and Dialysis, Internal Medicine III, Medizinische Universität Wien, Vienna, Austria, Division of Nephrology Dialysis and Transplantation, Policlinico, 70124 Bari, Italy, Nephrology Department, Hospital Universitario de Bellvitge, Barcelona, Spain, Renal Unit, Kidney Transplantation Center, ‘Leonardo Sciascia’ Civic Hospital, Palermo, Italy and Director of Renal and Urology, University of Sydney, Westmead Hospital, Westmead, NSW</wicri:regionArea>
<orgName type="university">Université de Barcelone</orgName>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Schena, F Paolo" sort="Schena, F Paolo" uniqKey="Schena F" first="F. Paolo" last="Schena">F. Paolo Schena</name>
<affiliation wicri:level="4">
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Servei de Nefrologia I Transplantament Renal, Renal Transplant Unit, Hospital Clinic, Universitat de Barcelona, 170, Villarroel, Jefe de Servico, Servico de Oncología Médica, Hospital del Mar-IMAS, Paseo Maritimo 25-29, Barcelona 08003, Spain, Cologne General Hospital, Merheim Medical Centre, Koeln-Merheim, Germany, Department of Nephrology and Transplantation, Laiko Hospital, Athens, Greece, ITERT, Department of Nephrology and Clinical Immunology, 30 Bd Jean Monnet, CHU Nantes, 44093 Nantes, Cedex 01, France, Department of Nephrology, Leiden University Medical Center, NL-2333ZA Leiden, The Netherlands, Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, University Clinic Charité, Campus Charité Mitte, Department of Nephrology, Berlin, Germany, Surgical Department, Rikshospitalet University Hospital, Oslo, Norway, Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Spain, Division of Nephrology and Dialysis, Internal Medicine III, Medizinische Universität Wien, Vienna, Austria, Division of Nephrology Dialysis and Transplantation, Policlinico, 70124 Bari, Italy, Nephrology Department, Hospital Universitario de Bellvitge, Barcelona, Spain, Renal Unit, Kidney Transplantation Center, ‘Leonardo Sciascia’ Civic Hospital, Palermo, Italy and Director of Renal and Urology, University of Sydney, Westmead Hospital, Westmead, NSW</wicri:regionArea>
<orgName type="university">Université de Barcelone</orgName>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Ser N, Daniel" sort="Ser N, Daniel" uniqKey="Ser N D" first="Daniel" last="Ser N">Daniel Ser N</name>
<affiliation wicri:level="4">
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Servei de Nefrologia I Transplantament Renal, Renal Transplant Unit, Hospital Clinic, Universitat de Barcelona, 170, Villarroel, Jefe de Servico, Servico de Oncología Médica, Hospital del Mar-IMAS, Paseo Maritimo 25-29, Barcelona 08003, Spain, Cologne General Hospital, Merheim Medical Centre, Koeln-Merheim, Germany, Department of Nephrology and Transplantation, Laiko Hospital, Athens, Greece, ITERT, Department of Nephrology and Clinical Immunology, 30 Bd Jean Monnet, CHU Nantes, 44093 Nantes, Cedex 01, France, Department of Nephrology, Leiden University Medical Center, NL-2333ZA Leiden, The Netherlands, Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, University Clinic Charité, Campus Charité Mitte, Department of Nephrology, Berlin, Germany, Surgical Department, Rikshospitalet University Hospital, Oslo, Norway, Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Spain, Division of Nephrology and Dialysis, Internal Medicine III, Medizinische Universität Wien, Vienna, Austria, Division of Nephrology Dialysis and Transplantation, Policlinico, 70124 Bari, Italy, Nephrology Department, Hospital Universitario de Bellvitge, Barcelona, Spain, Renal Unit, Kidney Transplantation Center, ‘Leonardo Sciascia’ Civic Hospital, Palermo, Italy and Director of Renal and Urology, University of Sydney, Westmead Hospital, Westmead, NSW</wicri:regionArea>
<orgName type="university">Université de Barcelone</orgName>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Sparacino, Vito" sort="Sparacino, Vito" uniqKey="Sparacino V" first="Vito" last="Sparacino">Vito Sparacino</name>
<affiliation wicri:level="4">
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Servei de Nefrologia I Transplantament Renal, Renal Transplant Unit, Hospital Clinic, Universitat de Barcelona, 170, Villarroel, Jefe de Servico, Servico de Oncología Médica, Hospital del Mar-IMAS, Paseo Maritimo 25-29, Barcelona 08003, Spain, Cologne General Hospital, Merheim Medical Centre, Koeln-Merheim, Germany, Department of Nephrology and Transplantation, Laiko Hospital, Athens, Greece, ITERT, Department of Nephrology and Clinical Immunology, 30 Bd Jean Monnet, CHU Nantes, 44093 Nantes, Cedex 01, France, Department of Nephrology, Leiden University Medical Center, NL-2333ZA Leiden, The Netherlands, Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, University Clinic Charité, Campus Charité Mitte, Department of Nephrology, Berlin, Germany, Surgical Department, Rikshospitalet University Hospital, Oslo, Norway, Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Spain, Division of Nephrology and Dialysis, Internal Medicine III, Medizinische Universität Wien, Vienna, Austria, Division of Nephrology Dialysis and Transplantation, Policlinico, 70124 Bari, Italy, Nephrology Department, Hospital Universitario de Bellvitge, Barcelona, Spain, Renal Unit, Kidney Transplantation Center, ‘Leonardo Sciascia’ Civic Hospital, Palermo, Italy and Director of Renal and Urology, University of Sydney, Westmead Hospital, Westmead, NSW</wicri:regionArea>
<orgName type="university">Université de Barcelone</orgName>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Chapman, Jeremy R" sort="Chapman, Jeremy R" uniqKey="Chapman J" first="Jeremy R." last="Chapman">Jeremy R. Chapman</name>
<affiliation wicri:level="4">
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Servei de Nefrologia I Transplantament Renal, Renal Transplant Unit, Hospital Clinic, Universitat de Barcelona, 170, Villarroel, Jefe de Servico, Servico de Oncología Médica, Hospital del Mar-IMAS, Paseo Maritimo 25-29, Barcelona 08003, Spain, Cologne General Hospital, Merheim Medical Centre, Koeln-Merheim, Germany, Department of Nephrology and Transplantation, Laiko Hospital, Athens, Greece, ITERT, Department of Nephrology and Clinical Immunology, 30 Bd Jean Monnet, CHU Nantes, 44093 Nantes, Cedex 01, France, Department of Nephrology, Leiden University Medical Center, NL-2333ZA Leiden, The Netherlands, Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, University Clinic Charité, Campus Charité Mitte, Department of Nephrology, Berlin, Germany, Surgical Department, Rikshospitalet University Hospital, Oslo, Norway, Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Spain, Division of Nephrology and Dialysis, Internal Medicine III, Medizinische Universität Wien, Vienna, Austria, Division of Nephrology Dialysis and Transplantation, Policlinico, 70124 Bari, Italy, Nephrology Department, Hospital Universitario de Bellvitge, Barcelona, Spain, Renal Unit, Kidney Transplantation Center, ‘Leonardo Sciascia’ Civic Hospital, Palermo, Italy and Director of Renal and Urology, University of Sydney, Westmead Hospital, Westmead, NSW</wicri:regionArea>
<orgName type="university">Université de Barcelone</orgName>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<country wicri:rule="url">Australie</country>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series>
<title level="j">Nephrology Dialysis Transplantation</title>
<idno type="ISSN">0931-0509</idno>
<imprint>
<publisher>Oxford University Press</publisher>
<date type="published" when="2007-05">2007-05</date>
<biblScope unit="volume">22</biblScope>
<biblScope unit="supplement">suppl_1</biblScope>
<biblScope unit="page" from="36">i36</biblScope>
<biblScope unit="page" to="41">i41</biblScope>
</imprint>
<idno type="ISSN">0931-0509</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<idno type="ISSN">0931-0509</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Clinical management</term>
<term>Extrarenal dialysis</term>
<term>Guidance</term>
<term>Hemodialysis</term>
<term>Immunosuppression</term>
<term>Malignant tumor</term>
<term>Renal failure</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Conduite à tenir</term>
<term>Epuration extrarénale</term>
<term>Guidage</term>
<term>Hémodialyse</term>
<term>Immunodépression</term>
<term>Insuffisance rénale</term>
<term>Tumeur maligne</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract">Increasing success in renal transplantation and longer patient survival has meant that post-transplant malignancies are having an increasing impact on long-term graft and patient survival. Choice of the immunosuppressive agents provides one of the controllable risk factors for the development of malignancies in this population. Calcineurin inhibitors (CNIs) are associated with an increased incidence of cancers, whereas the proliferation signal inhibitors (PSIs), everolimus and sirolimus have demonstrated anti-oncogenic effects in pre-clinical models and are currently being investigated as anti-cancer agents in clinical trials. There is increasing evidence demonstrating a lower incidence of post-transplant malignancies in renal transplant recipients receiving PSI-based immunosuppression compared with those receiving CNIs. Conversion from CNIs to PSIs has been shown to lead to the regression of Kaposi's sarcoma in renal transplant recipients and is now part of accepted standard care for this tumour in this setting. The anti-cancer properties of PSI-based regimens have the potential to combine the dual benefits of immunosuppression without the use of CNIs and the direct anti-oncogenic effects through their inhibition of the mammalian target of rapamycin (mTOR) signalling pathway. In the absence of formal clinical trial evidence on the best way to use PSIs in this setting, a workshop was held to provide practical guidance on immunosuppressive strategies in the context of malignancy, given the current state of knowledge.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Australie</li>
</country>
<region>
<li>Catalogne</li>
</region>
<settlement>
<li>Barcelone</li>
</settlement>
<orgName>
<li>Université de Barcelone</li>
</orgName>
</list>
<tree>
<country name="Australie">
<region name="Catalogne">
<name sortKey="Campistol, Josep M" sort="Campistol, Josep M" uniqKey="Campistol J" first="Josep M." last="Campistol">Josep M. Campistol</name>
</region>
<name sortKey=" Yen, Ole" sort=" Yen, Ole" uniqKey=" Yen O" first="Ole" last=" Yen">Ole Yen</name>
<name sortKey="Albanell, Joan" sort="Albanell, Joan" uniqKey="Albanell J" first="Joan" last="Albanell">Joan Albanell</name>
<name sortKey="Arns, Wolfgang" sort="Arns, Wolfgang" uniqKey="Arns W" first="Wolfgang" last="Arns">Wolfgang Arns</name>
<name sortKey="Boletis, Ioannis" sort="Boletis, Ioannis" uniqKey="Boletis I" first="Ioannis" last="Boletis">Ioannis Boletis</name>
<name sortKey="Chapman, Jeremy R" sort="Chapman, Jeremy R" uniqKey="Chapman J" first="Jeremy R." last="Chapman">Jeremy R. Chapman</name>
<name sortKey="Chapman, Jeremy R" sort="Chapman, Jeremy R" uniqKey="Chapman J" first="Jeremy R." last="Chapman">Jeremy R. Chapman</name>
<name sortKey="Dantal, Jacques" sort="Dantal, Jacques" uniqKey="Dantal J" first="Jacques" last="Dantal">Jacques Dantal</name>
<name sortKey="De Fijter, J W" sort="De Fijter, J W" uniqKey="De Fijter J" first="J. W." last="De Fijter">J. W. De Fijter</name>
<name sortKey="Mortensen, Svend Aage" sort="Mortensen, Svend Aage" uniqKey="Mortensen S" first="Svend Aage" last="Mortensen">Svend Aage Mortensen</name>
<name sortKey="Neumayer, Hans Hellmut" sort="Neumayer, Hans Hellmut" uniqKey="Neumayer H" first="Hans-Hellmut" last="Neumayer">Hans-Hellmut Neumayer</name>
<name sortKey="Pascual, Julio" sort="Pascual, Julio" uniqKey="Pascual J" first="Julio" last="Pascual">Julio Pascual</name>
<name sortKey="Pohanka, Erich" sort="Pohanka, Erich" uniqKey="Pohanka E" first="Erich" last="Pohanka">Erich Pohanka</name>
<name sortKey="Schena, F Paolo" sort="Schena, F Paolo" uniqKey="Schena F" first="F. Paolo" last="Schena">F. Paolo Schena</name>
<name sortKey="Ser N, Daniel" sort="Ser N, Daniel" uniqKey="Ser N D" first="Daniel" last="Ser N">Daniel Ser N</name>
<name sortKey="Sparacino, Vito" sort="Sparacino, Vito" uniqKey="Sparacino V" first="Vito" last="Sparacino">Vito Sparacino</name>
</country>
</tree>
</affiliations>
</record>

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