title: Failure of cyclosporine to induce graft-vs-host disease or graft-vs-leukemia after syngeneic bone marrow transplantation in mice.
abstract: Cyclosporine administration can result in graft-vs-host disease (GVHD) after syngeneic or autologous bone marrow transplantation (BMT). However, data on its anti-tumor effects are limited. We have tried to produce cyclosporine-induced GVHD or graft-vs-leukemia (GVL) against two Ia-bearing murine leukemias. BALB/c mice undergoing syngeneic BMT after total-body irradiation received 1 mg/kg or 10 mg/kg cyclosporine or dextrose intraperitoneally for 30 days post-transplant, followed by 5 x 10(3) BCL1 murine leukemia cells 1 or 3 weeks after stopping cyclosporine. Similarly, SJL/J mice undergoing syngeneic BMT received 10 mg/kg cyclosporine or dextrose intraperitoneally for 30 days post-transplant, and were inoculated with 5 x 10(3) or 10(5) murine acute myeloid leukemia (mAML) cells 3 weeks after stopping cyclosporine. No clinical or histological evidence of GVHD was seen, and leukemia-free and overall survival was similar with cyclosporine and dextrose. We conclude that under the experimental conditions used, it is not possible to induce syngeneic GVHD with cyclosporine in BALB/c or SJL/J mice. In the absence of GVHD, this approach is also not associated with any GVL effect against murine leukemias BCL1 and mAML.
authors.affiliation: Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: U
authors.initials: U
authors.lastname: Vourka-Karussis
authors.forename: J
authors.initials: J
authors.lastname: Mehta
authors.forename: S
authors.initials: S
authors.lastname: Slavin
authors.forename: L
authors.initials: L
authors.lastname: Weiss
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016572:Cyclosporine / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D011828:Radiation Chimera; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D014916:Whole-Body Irradiation
chemical_list: D016572:Cyclosporine