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.