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Further Development of a Successful Protocol of Graft versus Leukemia without Fatal Graft-versus-Host Disease in AKR Mice¹

Division of Clinical Hematology, Department of Medicine [S. J. C., L. J. F., J. D. S., R. J. K., M. M. A.], and Department of Pathology [A. R. E.], Rhode Island Hospital, Providence, Rhode Island 02902

We previously reported a successful model for treatment of BW 5147 leukemia in AKR mice by adoptive immunotherapy using allogeneic spleen cells from C57BL/6 mice. The leukemia cells were given 3 days before initiation of therapy. Graft-versus-host reaction was prevented by treatment with spleen cells from a second allogeneic strain (CBA), followed by cyclophosphamide and syngeneic spleen cells. We now show that it is not necessary to use syngeneic spleen cells in the final transplant since H-2-compatible, allogeneic CBA cells are as effective. In addition, it is possible to initiate successful therapy 5 days after leukemia implantation providing that the initial cyclophosphamide, given in two doses of 100 mg/kg each and spaced 7 days apart, is administered prior to establishment of graft-versus-host reaction. Higher single doses of drug were followed by fatal graft-versus-host disease.

¹ This research was supported in part by the George V. Meehan Fund-Clinical Research in Blood Diseases, the Phyllis Kimball Johnstone and H. Earie Kimball Foundation, and the Louis and Goldie Chester Memorial Fund.

Received 9/12/75. Accepted 7/ 6/77.