Immunosuppressive therapy and post-transplant malignancy

Abstract

Organ transplantation is a well-established method for the therapy of end-stage organ failure. The emergence of novel immunosuppressive regimens has reduced the risk of rejection and extended the life expectancy of organ recipients. The long-term outcome of these patients is now challenged by life-threatening complications such as cardiovascular disease, infections and post-transplant malignancies. Malignancy is a well-recognized complication of transplantation and can manifest as de novo cancer, as a recurrence of a pre-existing malignancy or from transmission of malignancy from the donor. Recent studies show that tumour incidence increases with time after organ transplantation and is related to the intensity of immunosuppression [1,2]. Overall, a 3to 4-fold increased incidence of cancer has been observed in transplant patients compared with age-matched controls in the general population. During immunosuppressive therapy, there is a higher frequency of some relatively rare tumours that tend to be biologically more aggressive than those that occur in the general population [3]. The relative risk for developing skin cancer in allografted patients is increased up to 70% in regions with high sun exposure [4]. Post-transplantation lymphoproliferative disorder (PTLD) occurs in up to 11% of renal transplant recipients and holds the major cause for cancer-related mortality. There is a 400to 500-fold increase in Kaposi sarcoma compared with controls of the same ethnic origin and a 100-fold increase in vulval and anal carcinomas in transplant recipients [5]. The aetiology of post-transplant malignancy is believed to be multifactorial in nature and probably involves impaired immunosurveillance of the host, direct carcinogenic effects of some immunosuppressive agents and de-