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

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 C(2) 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-C(2) regimen. When age was considered, only patients < or =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 C(2) monitoring or in younger patients of < or =50 years is associated with a higher early de novo cancer risk after LTx.

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  • Authors+Show Affiliations

    ,

    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.

    , , , , , , , ,

    Source

    MeSH

    Adolescent
    Adult
    Age Factors
    Aged
    Cyclosporine
    Female
    Graft Rejection
    Humans
    Immunosuppression
    Immunosuppressive Agents
    Incidence
    Liver Transplantation
    Male
    Middle Aged
    Monitoring, Immunologic
    Monitoring, Physiologic
    Neoplasms
    Retrospective Studies
    Risk Factors
    Survival Rate
    Tacrolimus
    Young Adult

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20583092

    Citation

    Tjon, Angela S W., et al. "Increased Incidence of Early De Novo Cancer in Liver Graft Recipients Treated With Cyclosporine: an Association With C2 Monitoring and Recipient Age." Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, vol. 16, no. 7, 2010, pp. 837-46.
    Tjon AS, Sint Nicolaas J, Kwekkeboom J, et al. Increased incidence of early de novo cancer in liver graft recipients treated with cyclosporine: an association with C2 monitoring and recipient age. Liver Transpl. 2010;16(7):837-46.
    Tjon, A. S., Sint Nicolaas, J., Kwekkeboom, J., de Man, R. A., Kazemier, G., Tilanus, H. W., ... Metselaar, H. J. (2010). Increased incidence of early de novo cancer in liver graft recipients treated with cyclosporine: an association with C2 monitoring and recipient age. Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 16(7), pp. 837-46. doi:10.1002/lt.22064.
    Tjon AS, et al. Increased Incidence of Early De Novo Cancer in Liver Graft Recipients Treated With Cyclosporine: an Association With C2 Monitoring and Recipient Age. Liver Transpl. 2010;16(7):837-46. PubMed PMID: 20583092.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Increased incidence of early de novo cancer in liver graft recipients treated with cyclosporine: an association with C2 monitoring and recipient age. AU - Tjon,Angela S W, AU - Sint Nicolaas,Jerome, AU - Kwekkeboom,Jaap, AU - de Man,Robert A, AU - Kazemier,Geert, AU - Tilanus,Hugo W, AU - Hansen,Bettina E, AU - van der Laan,Luc J W, AU - Tha-In,Thanyalak, AU - Metselaar,Herold J, PY - 2010/6/29/entrez PY - 2010/6/29/pubmed PY - 2010/11/3/medline SP - 837 EP - 46 JF - Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society JO - Liver Transpl. VL - 16 IS - 7 N2 - 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 C(2) 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-C(2) regimen. When age was considered, only patients < or =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 C(2) monitoring or in younger patients of < or =50 years is associated with a higher early de novo cancer risk after LTx. SN - 1527-6473 UR - https://www.unboundmedicine.com/medline/citation/20583092/Increased_incidence_of_early_de_novo_cancer_in_liver_graft_recipients_treated_with_cyclosporine:_an_association_with_C2_monitoring_and_recipient_age_ L2 - https://doi.org/10.1002/lt.22064 DB - PRIME DP - Unbound Medicine ER -