MALIGNANT NEOPLASMS IN CYCLOSPORINE-A-INDUCED AUTOIMMUNITY (CYA-AI)

Lethally X-irradiated LEW rats reconstituted with syngeneic bone marro w and given low-dose Cyclosporine A (CyA) for 5 weeks develop, after w ithdrawal of CyA, symptoms of disease resembling graft-vs.-host diseas e (GVHD) as seen after allogeneic bone-marrow transplantation. Symptom s of disease may include acute dermatitis and chronic disease resembli ng scleroderma, Since anti-class II MHC cytotoxic lymphocytes are gene rated in this model, it has been proposed as an anti-tumor regimen in humans. We now report that LEW rats treated according to this protocol may, after cessation of CyA administration, paradoxically develop mal ignant neoplasms, Of 48 experimental animals, 31 developed rapidly pro gressive subcutaneous and/or intracutaneous tumors commencing at 6 wee ks, 13 weeks and 6 months after cessation of CyA. Tumors were of mesen chymal origin, usually high-grade sarcoma, adenocarcinoma or both mese nchymal and epithelial tumors, Such tumor incidence exceeded the incid ence of tumor growth in X-irradiated controls, and in rats subjected t o thymectomy prior to X-irradiation and CyA administration, CyA by its elf induced no tumors, Our results show that total body X-irradiation is required for tumor development but that the presence of CyA-induced autoimmune disease increases the incidence significantly. (C) 1997 Wi ley-Liss, Inc.