Post-transplant malignancy: the role of immunosuppression

Immunosuppressed organ allograft recipients have a 3- to 4-fold increased risk of developing tumours, but the risk of developing certain cancers is increased several hundredfold. With the exception of skin and lip cancers, most of the common malignancies seen in the general population are not increased in incidence. Instead, there is a higher frequency of some relatively rare tumours, including post-transplant lymphomas and lymphoproliferative disorders (PTLD), Kaposi's sarcoma (KS), renal carcinomas, in situ carcinomas of the uterine cervix, hepatobiliary carcinomas, anogenital carcinomas and various sarcomas (excluding KS). Skin and lip cancers present some unusual features: a remarkable frequency of KS, reversal of the ratio of basal to squamous cell carcinomas seen in the general population, the young age of the patients, and the high incidence of multiple tumours (in 43% of the patients). Anogenital cancers occur at a much younger age than in the general population. Salient features of PTLD are the high frequency of Epstein-Barr virus-related lesions, frequent involvement of extranodal sites, a marked predilection for the brain and frequent allograft involvement. As the immunosuppressed state per se and various potentially oncogenic viruses play a major role in causing these cancers, preventative measures include reducing immunosuppression to the lowest level compatible with good allograft function and prophylactic measures against certain virus infections. Reduction of exposure to sunlight may also decrease the incidence of skin cancer. In addition to conventional treatments (resection, radiation therapy, chemotherapy) patients may receive antiviral drugs, interferon-alpha and various other manipulations of the immune system. A significant percentage of cases of PTLD and KS respond to reduction or cessation of immunosuppressive therapy.