Increased incidence of early de novo cancer in liver graft recipients treated with cyclosporine: An association with C2 monitoring and recipient age

Authors

  • Angela S. W. Tjon,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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    • A.S.W. Tjon was financially supported by Biotest Pharma, Dreieich, Germany

  • Jerome Sint Nicolaas,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Jaap Kwekkeboom,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Robert A. de Man,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Geert Kazemier,

    1. Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Hugo W. Tilanus,

    1. Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Bettina E. Hansen,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
    2. Department of Biostatistics, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Luc J. W. van der Laan,

    1. Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Thanyalak Tha-In,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
    2. Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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  • Herold J. Metselaar

    Corresponding author
    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
    • Erasmus MC University Medical Centre, Department of Gastroenterology and Hepatology, Room Hs-514, 3015 CE Rotterdam, The Netherlands
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    • Telephone: +3110-703 29 63; FAX: +3110-703 51 72


  • See Editorial on Page 809

Abstract

The goal of this study was to determine the risk factors for de novo cancer after liver transplantation (LTx). Retrospective analyses were performed in 385 LTx patients who underwent transplantation between 1986 and 2007. In total, 50 (13.0%) recipients developed de novo malignancy. The cumulative incidence of de novo cancer at 1, 5, 10, and 15 years after LTx was 2.9% ± 0.9%, 10.5% ± 1.8%, 19.4% ± 3.0%, and 33.6% ± 6.8%, respectively. The standardized incidence ratio of malignancy in LTx patients compared to the general population was 2.2 (95% confidence interval: 1.6-2.8). After excluding posttransplant lymphoproliferative disorder and skin cancer, patients with de novo cancer had a significantly lower survival rate compared to recipients who remained cancer-free. The identified univariate risk factors for de novo cancer were cyclosporine A (CsA) treatment, time period of LTx, and recipient age. In multivariate analysis, only CsA treatment emerged as an independent risk factor for de novo cancer, which was attributed to more aggressive cancer types. A surprising finding was that CsA treatment specifically enhanced cancer risk in patients who underwent transplantation after 2004, when C2 monitoring (blood concentration at 2 hours postdose) was introduced. In addition, these patients showed a significantly lower acute rejection rate, which might reflect a more robust immunosuppressive status caused by the CsA-C2 regimen. When age was considered, only patients ≤50 years had a higher cancer rate when treated with CsA compared to treatment with tacrolimus. Our data suggest that, compared to tacrolimus treatment, CsA treatment with C2 monitoring or in younger patients of ≤50 years is associated with a higher early de novo cancer risk after LTx. Liver Transpl 16:837–846, 2010. © 2010 AASLD.

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