Literature DB >> 32605413

The impact of switching to mTOR inhibitor-based immunosuppression on long-term non-melanoma skin cancer incidence and renal function in kidney and liver transplant recipients.

Susan L Murray1,2, Fergus E Daly1, Patrick O'Kelly1, Eamonn O'Leary3, Sandra Deady3, James P O'Neill4, Alexander Dudley5, Nicholas R Rutledge5, Aiden McCormick5, Diarmuid D Houlihan5, Yvonne Williams1, Patrick G Morris6, Siona Ni Raghallaigh7, Fergal J Moloney8, Donal J Sexton1, Peter J Conlon1,2.   

Abstract

Background: Solid organ transplantation is associated with increased risk of non-melanoma skin cancer. Studies with short follow up times have suggested a reduced occurrence of these cancers in recipients treated with mammalian target of rapamycin inhibitors as maintenance immunosuppression. We aimed to describe the occurrence of skin cancers in renal and liver transplant recipients switched from calcineurin inhibitor to sirolimus-based regimes.
Methods: We performed a retrospective study of sirolimus conversion within the Irish national kidney and liver transplant programs. These data were linked with the National Cancer Registry Ireland to determine the incidence of NMSC among these recipients. The incidence rate ratio (IRR) for post versus pre-conversion NMSC rates are referred in this study as an effect size with [95% confidence interval].
Results: Of 4,536 kidney transplants and 574 liver transplants functioning on the 1 January 1994 or transplanted between 1 January 1994 and 01 January 1994 and 01 January 2015, 85 kidney and 88 liver transplant recipients were transitioned to sirolimus-based immunosuppression. In renal transplants, the rate of NMSC was 131 per 1000 patient years pre-switch to sirolimus, and 68 per 1000 patient years post switch, with adjusted effect size of 0.48 [0.31 - 0.74] (p = .001) following the switch. For liver transplant recipients, the rate of NMSC was 64 per 1,000 patient years pre-switch and 30 per 1,000 patient years post switch, with an adjusted effect size of 0.49 [0.22 - 1.09] (p .081). Kidney transplant recipients were followed up for a median 3.4 years. Liver transplants were followed for a median 6.6 years.Conclusions: In this study, the conversion of maintenance immunosuppression from calcineurin inhibitors to mTOR inhibitors for clinical indications did appear to reduce the incidence of NMSC in kidney and liver transplant recipients.

Entities:  

Keywords:  Immunosuppression; cancer; liver transplant; mTOR inhibitor; renal transplant; skin cancer

Mesh:

Substances:

Year:  2020        PMID: 32605413      PMCID: PMC7946013          DOI: 10.1080/0886022X.2020.1785499

Source DB:  PubMed          Journal:  Ren Fail        ISSN: 0886-022X            Impact factor:   2.606


  22 in total

Review 1.  Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

Authors:  A C Webster; V W Lee; J R Chapman; J C Craig
Journal:  Cochrane Database Syst Rev       Date:  2006-04-19

2.  Long-term results of conversion from calcineurin inhibitors to sirolimus in 150 maintenance kidney transplant patients.

Authors:  Cyril Garrouste; Nassim Kamar; Céline Guilbeau-Frugier; Joëlle Guitard; Laure Esposito; Laurence Lavayssière; Marie-Béatrice Nogier; Olivier Cointault; David Ribes; Lionel Rostaing
Journal:  Exp Clin Transplant       Date:  2012-04       Impact factor: 0.945

3.  Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States.

Authors:  Giorgia L Garrett; Paul D Blanc; John Boscardin; Amanda Abramson Lloyd; Rehana L Ahmed; Tiffany Anthony; Kristin Bibee; Andrew Breithaupt; Jennifer Cannon; Amy Chen; Joyce Y Cheng; Zelma Chiesa-Fuxench; Oscar R Colegio; Clara Curiel-Lewandrowski; Christina A Del Guzzo; Max Disse; Margaret Dowd; Robert Eilers; Arisa Elena Ortiz; Caroline Morris; Spring K Golden; Michael S Graves; John R Griffin; R Samuel Hopkins; Conway C Huang; Gordon Hyeonjin Bae; Anokhi Jambusaria; Thomas A Jennings; Shang I Brian Jiang; Pritesh S Karia; Shilpi Khetarpal; Changhyun Kim; Goran Klintmalm; Kathryn Konicke; Shlomo A Koyfman; Charlene Lam; Peter Lee; Justin J Leitenberger; Tiffany Loh; Stefan Lowenstein; Reshmi Madankumar; Jacqueline F Moreau; Rajiv I Nijhawan; Shari Ochoa; Edit B Olasz; Elaine Otchere; Clark Otley; Jeremy Oulton; Parth H Patel; Vishal Anil Patel; Arpan V Prabhu; Melissa Pugliano-Mauro; Chrysalyne D Schmults; Sarah Schram; Allen F Shih; Thuzar Shin; Seaver Soon; Teresa Soriano; Divya Srivastava; Jennifer A Stein; Kara Sternhell-Blackwell; Stan Taylor; Allison Vidimos; Peggy Wu; Nicholas Zajdel; Daniel Zelac; Sarah T Arron
Journal:  JAMA Dermatol       Date:  2017-03-01       Impact factor: 10.282

4.  Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial.

Authors:  Josefina Alberú; Michael D Pascoe; Josep M Campistol; Francesco P Schena; Maria Del Carmen Rial; Martin Polinsky; John F Neylan; Joan Korth-Bradley; Robert Goldberg-Alberts; Eric S Maller
Journal:  Transplantation       Date:  2011-08-15       Impact factor: 4.939

5.  Inhibition of calcineurin by FK506 protects against polyglutamine-huntingtin toxicity through an increase of huntingtin phosphorylation at S421.

Authors:  Raúl Pardo; Emilie Colin; Etienne Régulier; Patrick Aebischer; Nicole Déglon; Sandrine Humbert; Frédéric Saudou
Journal:  J Neurosci       Date:  2006-02-01       Impact factor: 6.167

6.  Aggressive behavior of nonmelanotic skin cancers in solid organ transplant recipients.

Authors:  David G Lott; Ryan Manz; Carl Koch; Robert R Lorenz
Journal:  Transplantation       Date:  2010-09-27       Impact factor: 4.939

7.  Subsequent squamous- and basal-cell carcinomas in kidney-transplant recipients after the first skin cancer: cumulative incidence and risk factors.

Authors:  Hermina C Wisgerhof; Jeroen R J Edelbroek; Johan W de Fijter; Geert W Haasnoot; Frans H J Claas; Rein Willemze; Jan N Bouwes Bavinck
Journal:  Transplantation       Date:  2010-05-27       Impact factor: 4.939

8.  Association of Sirolimus Use With Risk for Skin Cancer in a Mixed-Organ Cohort of Solid-Organ Transplant Recipients With a History of Cancer.

Authors:  Pritesh S Karia; Jamil R Azzi; Eliot C Heher; Victoria M Hills; Chrysalyne D Schmults
Journal:  JAMA Dermatol       Date:  2016-05-01       Impact factor: 10.282

9.  Variation in Nonmelanoma Skin Cancer Incidence by Treatment Modality Among Patients Receiving Multiple Kidney Transplants.

Authors:  Donal J Sexton; Patrick O'Kelly; Eamonn O'Leary; Susan Murray; Sandra Deady; Fergus Daly; Jim Egan; Diarmaid D Houlihan; P Aiden McCormick; Patrick G Morris; Siona Ni Raghallaigh; Fergal J Moloney; James Paul O'Neill; Peter J Conlon
Journal:  JAMA Dermatol       Date:  2019-05-01       Impact factor: 10.282

Review 10.  Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data.

Authors:  Greg A Knoll; Madzouka B Kokolo; Ranjeeta Mallick; Andrew Beck; Chieny D Buenaventura; Robin Ducharme; Rashad Barsoum; Corrado Bernasconi; Tom D Blydt-Hansen; Henrik Ekberg; Claudia R Felipe; John Firth; Lorenzo Gallon; Marielle Gelens; Denis Glotz; Jan Gossmann; Markus Guba; Ahmed Ali Morsy; Rebekka Salgo; Earnst H Scheuermann; Helio Tedesco-Silva; Stefan Vitko; Christopher Watson; Dean A Fergusson
Journal:  BMJ       Date:  2014-11-24
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  1 in total

Review 1.  Oh, the Mutations You'll Acquire! A Systematic Overview of Cutaneous Squamous Cell Carcinoma.

Authors:  Stephenie Droll; Xiaomin Bao
Journal:  Cell Physiol Biochem       Date:  2021-09-22
  1 in total

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