Autologous bone marrow grafts in dogs treated with lethal doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

Hematological and immunosuppressive effects of various single doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) were evaluated in the preclinical canine model. Immune function appeared not to be impaired by treatment with CCNU, but severe myelotoxicity contributed to the death of 3 of 4 dogs given 10 mg CCNU per kg and 5 of 5 dogs given 15 mg CCNU per kg within 10 days after drug administration. Infusions of autologous bone marrow protected 6 of 6 dogs receiving 15 mg CCNU per kg and 6 of 6 dogs receiving 20 mg CCNU per kg from lethal marrow failure. Dogs given 30 mg CCNU per kg and autologous marrow died within 7 days from severe gastrointestinal toxicity. We conclude that autologous bone marrow support may allow the use of high-dose CCNU regimens and thereby increase its therapeutic efficacy in the treatment of advanced cancer.