Malignancy in renal transplantation: opportunities with proliferation signal inhibitors
Guest editors’ introduction
1Director of Renal and Urology, Westmead Hospital, Westmead, NSW 2145, Australia and 2Director of the Nephrology and Urology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
Correspondence and offprint requests to: J.R. Chapman, Centre for Transplant and Renal Research, Millennium Institute, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. Tel: +61 2 9845 6349; Fax: +61 2 9845 8300 Email: Jeremy_Chapman{at}wsahs.nsw.gov.au
Keywords: immunosuppression; malignancy; proliferation signal inhibitors/mTOR inhibitors; renal transplantation
Patient survival after renal transplantation has improved considerably over the past 30 years [1]. Currently, patient survival rates of 95% at 1 year and 
90% at 5 years are realistic [2]; however, life expectancy remains far worse than in the general population [2].
Cardiovascular disease is the leading cause of death following renal transplantation in most countries, accounting for around 40–55% of all deaths [1], but post-transplant malignancies are becoming increasingly common and are fast becoming a major burden affecting long-term survival (Figure 1). The increasing incidence of post-transplant malignant tumours was first noted almost three decades ago [3,4]. Data show that, overall, there is a 3–5-fold increased incidence of malignant tumours after renal transplantation when compared with the age- and sex-matched general population [3,5–7] and the United States Renal Data System (USRDS), reports that 7.5% of deaths post-renal transplantation are attributed to malignancy [8].
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Compared with the general population, several types of malignancy occur more commonly in transplant recipients, are often more aggressive and offer worse prognosis [1]. In renal transplant recipients, skin cancers and lymphomas are among the most prevalent malignancies [2,3,9]. According to the USRDS database, the incidence of common malignancies, such as colon, lung and stomach, is approximately 2-fold higher after renal transplantation than in the general population [9,10]. These data are also observed in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), which reports that the incidence of more transplant-specific malignancies, such as Kaposi's sarcoma, can be as great as nearly 40-fold [2].
A variety of risk factors contribute to the incidence of cancer, including both conventional risk factors and those specific to transplant recipients. In transplant recipients, commonly known risk factors, such as oncogenic viruses, exposure to ultraviolet light, total sun burden, previous exposure to carcinogens, cigarette smoking, advanced age, geographical location and genetic predisposition, all contribute to cancer incidence. Immunosuppression, increasing recipient age and history of malignancy are also specific risk factors for the transplant population (Figure 2) [3,11–14]. The duration of immunosuppressive therapy, the intensity of therapy and the type of immunosuppressive agent all have an impact on the development of post-transplant malignancy, making the immunosuppressive regimen an important risk factor requiring consideration. The role of particular immunosuppressive agents on the outcome of post-transplant malignancies is controversial [15]. The use of immunosuppressive regimens that combine a variety of agents makes it difficult to isolate the effects of individual agents on post-transplant malignancies, thereby limiting the data available.
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The rising incidence of post-transplant malignancies has provoked both practical and academic interest. Specifically, the potential role of new immunosuppressive agents, the proliferation signal inhibitors (PSIs)/mammalian target of rapamycin (mTOR) inhibitors, in the prevention, modification and perhaps even treatment of post-transplant malignancies is both exciting and beneficial for this at-risk patient population [11].
The articles that constitute this supplement address the importance of malignancies following transplantation. The first article, by Dr Jacques Dantal (Nantes, France) and Dr Erich Pohanka (Vienna, Austria), provides a review of the current literature on the impact of post-transplant malignancies and the consequent effect on long-term organ survival. This review also describes risk factors for the development of malignancies, considering both conventional and transplant-specific factors. As previously mentioned, patient immunosuppression plays an important role in the development of post-transplant malignancy. Dr Alex Gutierrez-Dalmau and Dr Josep M. Campistol (Barcelona, Spain) addresses how the introduction of a new class of anti-proliferative immunosuppressants, PSIs, has affected the incidence and treatment of post-transplant malignancy. Promising data so far have demonstrated the benefits of PSI use, in both the prevention of post-transplant malignancy and advanced solid tumour management. Specific types of malignancy are more common in transplant recipients compared with the general population. The following articles briefly review the incidence and impact of three particularly relevant malignancies. Dr Josep M. Campistol (Barcelona, Spain) and Dr F. Paolo Schena (Bari, Italy) discuss Kaposi's sarcoma, highlighting the benefits of conversion to a PSI-based immunosuppressive regimen in these patients. Dr Hans de Fijter (Leiden, Netherlands) reviews non-melanoma skin cancer in renal transplant recipients, including clinical experience in the use of PSIs. To conclude this section, Dr Julio Pascual (Madrid, Spain) provides a brief overview of post-transplant lymphoproliferative disorders (PTLDs). The clinical experience of the use of PSIs discussed in the brief reviews on Kaposi's sarcoma, non-melanoma skin cancer and PTLD are combined from a number of centres across Europe and Australia.
Finally, clinical guidelines, developed at a workshop of transplant nephrologists, based on current data for the use of PSIs in the management of post-transplant malignancies after renal transplantation, are reported. Specifically, this article addresses questions such as how, when, in which patients and for which types of cancer PSI therapy could be beneficial in improving malignancy outcomes.
It is clear that malignancy represents one of the three major targets that must be tackled to reduce transplant patient mortality rates—notably, cardiovascular disease, infection and malignancy. Developing knowledge about the role of different immunosuppressive strategies thus remains a priority for clinical transplant programmes and their patients.
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Acknowledgement |
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 Top Acknowledgement References |
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Editorial assistance was provided by Ogilvy 4D.
Conflict of interest statement. The authors received an honorarium from Novartis Pharma AG for participation in the workshop in Rome, March 2006, on the role of everolimus in the management of post-transplant malignancies in renal transplantation.
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References |
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TopAcknowledgementReferences |
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- Ulrich C, Schmook T, Sachse MM, et al. (2004) Comparative epidemiology and pathogenic factors for nonmelanoma skin cancer in organ transplant patients. Dermatol Surg 30:622–627.[CrossRef][ISI][Medline]
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