Immunosuppression and Malignancy

The increasing use over the past decade of powerful immunosuppressive drugs provides an opportunity for testing the validity of the theory that cancer results from a breakdown of the body's "immunological surveillance." This concept, first proposed by L. Thomas' and since developed by Sir Macfarlane Burnet,2 holds that such a breakdown allows the proliferation of abnormal cells, with the eventual result of overt malignancy. Some four years ago reports from widely separated centres in Scotland, New Zealand, and the U.S.A. of reticulum cell sarcomas in patients on immunosuppresive therapy after renal transplantation brought the issues to attention. The occurrence of several cases of so rare a disease in only a few recipients of transplants could not easily be attributed to chance. Largely owing to the efforts of I. Penn and his colleagues at Denver, Colorado, who have kept an informal registry of malignant neoplasms in the recipients of organ transplants, other similar cases have been documented. So far at least 17 reticulum cell sarcomas and two unclassified lymphomas have been reported in approximately 5,000 recipients of transplants and of immunosuppressive treatment.3-5 Full details of one case of reticulum cell sarcoma involving the meninges have not yet been published,5 but of the remaining 18 cases 13 occurred in males and 5 in females 5± to 73 months after transplantation (mean 24 months). Ten of these cases followed transplants from a living donor. All patients received immunosuppressive treatment with azathioprine and prednisone, while 11 patients received additional immunosuppressive measures in the form of splenectomy (eight cases), antilymphocytic serum (five cases), or thymectomy (one case). All but three of the 18 patients are dead. In view of the fact that reticulum cell sarcoma usually spares the brain,5 it is of great interest that in nine of these cases that organ was involved, in six cases exclusively, while the two unclassified lymphomas were both confined to the brain. Though the frequency of these lymphomas is undoubtedly increased in recipients of transplants, the extent of the increase is not yet known precisely. Some crude estimates have been made, and at a time when 14 lymphomas (12 reticulum cell sarcomas) had been recorded among approximately 4,000 recipients of transplants the incidence was estimated to be increased 50-fold over that for reticuloses other than Hodgkin's disease in the age group 2049.6 Published incidence rates for reticulum cell sarcomas in the general population are often combined with those for lymphosar-