Transplant-Associated Skin Cancer: Role of Reducing Immunosuppression

Author: Marcy Neuburg MD 1
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  • 1 From the Medical College of Wisconsin and Froedtert Memorial Lutheran Hospital, Milwaukee, Wisconsin.

This article explores the role of reducing immunosuppression as a therapeutic strategy for the problem of transplant-associated skin cancer. The specific issue of immunosuppression reduction is based on a brief historic review of the epidemiology of skin cancer in transplant patients, followed by a description of the role of immunosuppression as a cause of skin cancer. Finally, the literature pertaining to the hypothesis that reducing immunosuppression in solid organ transplant recipients favorably impacts both the incidence of cutaneous malignancy and outcomes relating to individual aggressive malignancies is presented.

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Correspondence: Marcy Neuburg, MD, Medical College of Wisconsin and Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, WI 53226. E-mail: mneuburg@mcw.edu
  • 1.

    Merrill JP, Murray JE, Harrison JH. Successful homotransplantation of the human kidney between identical twins. JAMA 1956;160:277282.

  • 2.

    Calne RY. The rejection of renal homografts. Inhibition in dogs by 6-mercaptopurine. Lancet 1960;1:417418.

  • 3.

    Penn I, Halgrimson CG, Starzl TE. De novo malignant tumors in organ transplant recipients. Transplant Proc 1971;3:773778.

  • 4.

    Sheil AG, Disney AP, Mathew TH, Amiss N. De novo malignancy emerges as a major cause of morbidity and late failure in renal transplantation. Transplant Proc 1993;25:13831384.

    • Search Google Scholar
    • Export Citation
  • 5.

    Bouwes Bavinck JN, Hardie DR, Green A. The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study. Transplantation 1996;61:715721

    • Search Google Scholar
    • Export Citation
  • 6.

    Ong CS, Keogh AM, Kossard S. Skin cancer in Australian heart transplant recipients. J Am Acad Dermatol 1999;40:2734.

  • 7.

    Veness MJ, Quinn DI, Ong CS. Aggressive cutaneous malignancies following cardiothoracic transplantation: the Australian experience. Cancer 1999;85:17581764.

    • Search Google Scholar
    • Export Citation
  • 8.

    Fortina AB, Caforio AL, Piaserico S. Skin cancer in heart transplant recipients: frequency and risk factor analysis. J Heart Lung Transplant 2000;19:249255.

    • Search Google Scholar
    • Export Citation
  • 9.

    Ramsay HM, Fryer AA, Reece S. Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. Am J Kidney Dis 2000;36:167176.

    • Search Google Scholar
    • Export Citation
  • 10.

    Penn I. Post-transplant malignancy: the role of immunosuppression. Drug Saf 2000;23:101113.

  • 11.

    Martinez JC, Otley CC, Stasko T. Transplant-skin cancer collaborative. Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study. Arch Dermatol 2003;139:301306.

    • Search Google Scholar
    • Export Citation
  • 12.

    Kasiske BL, Snyder JJ, Gilbertson DT. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4:905913.

  • 13.

    Moloney FJ, Comber H, O'Lorcain P. A population-based study of skin cancer incidence and prevalence in renal transplant recipients. Br J Dermatol 2006;154:498504.

    • Search Google Scholar
    • Export Citation
  • 14.

    Euvrard S, Kanitakis J, Decullier E. Subsequent skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma. Transplantation 2006;81:10931100.

    • Search Google Scholar
    • Export Citation
  • 15.

    US Transplant. OPTN/SRTR 2006 Annual Report, Table 1.14. People living with a functioning graft at year end by organ, 1996–2005 (slide 12). Available at: http://www.ustransplant.org/csr/current/fastfacts/ppt_slides.aspx. Accessed February 26, 2007.

    • Search Google Scholar
    • Export Citation
  • 16.

    Kelly GE, Meikle W, Sheil AG. Effects of immunosuppressive therapy on the induction of skin tumors by ultraviolet irradiation in hairless mice. Transplantation 1987;44:429434.

    • Search Google Scholar
    • Export Citation
  • 17.

    Sorensen HT, Mellemkjaer L, Skriver MV. Skin cancers and non-Hodgkin lymphoma among users of systemic glucocorticoids: a population-based cohort study. J Natl Cancer Inst 2004;96:709711.

    • Search Google Scholar
    • Export Citation
  • 18.

    Karagas MR, Cushing GL, Greenberg. Non-melanoma skin cancers and glucocorticoid therapy. Br J Cancer 2001;85:683686.

  • 19.

    Shuttleworth D, Marks R, Griffin PJ. Epidermal dysplasia and cyclosporine therapy in renal transplant patients: a comparison with azathioprine. Br J Dermatol 1989;120:551554.

    • Search Google Scholar
    • Export Citation
  • 20.

    Kehinde EO, Petermann A, Morgan JD. Triple therapy and incidence of de novo cancer in renal transplant recipients. Br J Surg 1994;81:985986.

    • Search Google Scholar
    • Export Citation
  • 21.

    Glover MT, Deeks JJ, Raftery MJ. Immunosuppression and risk of non-melanoma skin cancer in renal transplant recipients. Lancet 1997;349:398.

  • 22.

    Hiesse C, Rieu P, Kriaa F. Malignancy after renal transplantation: analysis of incidence and risk factors in 1,700 patients followed during a 25-year period. Transplant Proc 1997;29:831833.

    • Search Google Scholar
    • Export Citation
  • 23.

    Dantal J, Hourmant M, Cantarovich D. Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomized comparison of two cyclosporin regimens. Lancet 1998:351:623628.

    • Search Google Scholar
    • Export Citation
  • 24.

    Jensen P, Hansen S, Moller B. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol 1999;40:177186.

    • Search Google Scholar
    • Export Citation
  • 25.

    Mita MM, Mita A, Rowinsky EK. The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol Ther 2003;2(suppl 1):S169177.

    • Search Google Scholar
    • Export Citation
  • 26.

    Kahan BD, Knight R, Schoenberg L. Ten years of sirolimus therapy for human renal transplantation: the University of Texas at Houston experience. Transplant Proc 2003;35(suppl 3A):25S34S.

    • Search Google Scholar
    • Export Citation
  • 27.

    Mathew T, Kries H, Friend P. Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transplant 2004;18:446449.

    • Search Google Scholar
    • Export Citation
  • 28.

    Kahan BD, Yakupoglu YK, Schoenberg L. Low incidence of malignancy among sirolimus/cyclosporine-treated renal transplant recipients. Transplantation 2005;80:749758.

    • Search Google Scholar
    • Export Citation
  • 29.

    Kauffman HM, Cherikh W, Cheng Yulin. Maintenance Immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies. Transplantation 2005;80:883889.

    • Search Google Scholar
    • Export Citation
  • 30.

    Tiu J, Li H, Rassekh C. Molecular basis of posttransplant squamous cell carcinoma: the potential role of cyclosporine A in carcinogenesis. Laryngoscope 2006;116:762769.

    • Search Google Scholar
    • Export Citation
  • 31.

    Khariwala SS, Kjaergaard J, Lorenz R. Everolimus (RAD) inhibits in vivo growth of murine squamous cell carcinoma (SCC VII). Laryngoscope 2006;116:814820.

    • Search Google Scholar
    • Export Citation
  • 32.

    Mazariegos GV, Reyes J, Marino IR. Weaning of immunosuppression in liver transplant recipients. Transplantation 1997;63:243249.

  • 33.

    Oike F, Yokoi A, Nishimura E. Complete withdrawal of immunosuppression in living donor liver transplantation. Transplant Proc 2002;34:1521.

  • 34.

    Mozzanica N, Cattaneo A, Fracchiolla N. Posttransplantation cutaneous B-cell lymphoma with monoclonal Epstein-Barr virus infection, responding to acyclovir and reduction in immunosuppression. J Heart Lung Transplant 1997;16:964968.

    • Search Google Scholar
    • Export Citation
  • 35.

    Tsai DE, Hardy CL, Tomaszewski JE. Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients. Transplantation 2001;71:10761088.

    • Search Google Scholar
    • Export Citation
  • 36.

    Duman S, Toz H, Asci G. Successful treatment of post-transplant Kaposi's sarcoma by reduction of immunosuppression. Nephrol Dial Transplant 2002;17:892896.

    • Search Google Scholar
    • Export Citation
  • 37.

    Otley CC, Coldiron BM, Stasko T. Decreased skin cancer after cessation of therapy with transplant-associated immunosuppressants. Arch Dermatol 2001;137:459463.

    • Search Google Scholar
    • Export Citation
  • 38.

    Fortina AB, Piaserico S, Caforio AL. Immunosuppressive level and other risk factors for basal cell carcinoma and squamous cell carcinoma in heart transplant recipients. Arch Dermatol 2004;140:10791085.

    • Search Google Scholar
    • Export Citation
  • 39.

    Soulillou JP, Giral M. Controlling the incidence of infection and malignancy by modifying immunosuppression. Transplantation 2001;72(suppl 12):S8993.

    • Search Google Scholar
    • Export Citation
  • 40.

    Kirk AD, Mannon RB, Swanson SJ. Strategies for minimizing immunosuppression in kidney transplantation. Transplant Int 2005;18:214.

  • 41.

    Otley CC, Maragh SL. Reduction of immunosuppression for transplant-associated skin cancer: rationale and evidence of efficacy. Dermatol Surg 2005;31:163168.

    • Search Google Scholar
    • Export Citation
  • 42.

    EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: long-term management of the transplant recipient. IV.6.2. Cancer risk after renal transplantation. Skin cancers: prevention and treatment. Nephrol Dial Transplant 2002;17(suppl 4):3136.

    • Search Google Scholar
    • Export Citation
  • 43.

    Moloney FJ, Kelly PO, Kay EW. Maintenance versus reduction of immunosuppression in renal transplant recipients with aggressive squamous cell carcinoma. Dermatol Surg 2004;30:674678.

    • Search Google Scholar
    • Export Citation
  • 44.

    Otley CC, Berg D, Ulrich C. Reduction of immunosuppression for transplant-associated skin cancer: expert consensus survey. Br J Dermatol 2006;154:395400.

    • Search Google Scholar
    • Export Citation
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