Malignant tumors arising de novo in immuno-suppressed organ transplant recipients

Abstract

SUMMARYDe novo malignant tumors have been observed throughout the world in 75 chronic survivors of organ transplantation, including 16 of our own patients. The incidence of tumors was approximately 80 times greater than in the average population in a comparable age range. Chronic uremia may have predisposed to the development of some of the tumors, but this has not yet been proved. It seems clear that the predominant etiology was chronic immunosuppression post-transplantation. Forty-four of the patients had epithelial tumors and in 31 the lesions were of mesenchymal origin. On the average the malignancies appeared 29 months after transplantation. Lymphomas showed an unusual predilection for involvement of the central nervous system. Carcinomas of the skin, lip, and uterine cervix were successfully treated by conventional techniques. On the other hand, carcinomas of the thoracic or abdominal organs and mesenchymal tumors led or contributed to early death in most cases. For this reason drastic reduction or even discontinuance of immunosuppression should be considered in the management of these , latter tumors.

Combination Chemotherapy of Rauscher Leukemia and Ascites Tumors by Narcissus Alkaloid with Standard Drugs and Effect on Cellular Immunity

“…In cancer chemotherapy, the immunosuppres- 13 (11)(12)(13)(14)(15) 0/12 0 a The lo5 cells were inoculated ip to BALB/c inbred mice. The treatment schedule was the same as shown in Table 11.…”

“…sive activity of various anticancer drugs is one of the most unfavorable side effects (12). The narcissus alkaloid at the therapeutic dose was not inhibitory to humoral antibody production (1).…”

“…Many standard drugs possess strong or moderate immunosuppressive activity not only on humoral but also on cellular immunity which plays an important role in preventing the progression of tumor growth (12,14). The alkaloid has now been found to have no adverse effects on the cellular immunity as demonstrated by tests of PHA reactivity and allogeneic tumor rejection.…”

Conformational basis for the activation of adenylate cyclase by adenosine

“…The inhibition of rat liver 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) in rapidly proliferating tissue such as Yoshida sarcoma (73), of lymphocyte 5'-nucleotidase in chronic lymphocytic leukemia patients (74), and of 5'-nucleotidase in rat brain by methylxanthines (75) will act to decrease cAMP levels by decreasing the concentration of adenosine. There is an increased incidence of de novo tumors in individuals with primary immune deficiency diseases (76) and in patients whose immune system has been deliberately suppressed (77). The variations in adenosine deaminase activity, which disposes of adenosine and blocks the stimulation of adenylate cyclase by adenosine to increase cAMP levels and modify immune responses, seems to be correlated in leukemias (78,79) with the formation of adenosine by 5'-nucleotidase.…”

Suppression of Mixed Lymphocyte Culture by Uremic Adherent Spleen Cells and Peritoneal Macrophages Is Dependent on a Cyclophosphamide-Sensitive Cell

“…Delayed hypersensi tivity has been shown to be diminished in uremic pa tients [9,11,25], homograft survival is prolonged [9,19,28], and the antibody response of uremic patients to various antigens is diminished [9,II], Chronic uremic patients also have a higher incidence of malig nancies [16][17][18]23]. More recently, results from our laboratory indicate that the reactivity of spleen cells from uremic rats to mitogens is significantly sup pressed [3,6,7] and that this suppression is mediated by macrophages present in the spleen, the perito neum, and the lung of these animals [1,2].…”