Long-term survivors of mice bearing a transplanted leukemia have been obtained following treatment with a combination of amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea. The proportion of mice surviving at 28 days depended upon the order and timing of drug administration. Optimal results were obtained when 0.5 mg amphotericin B was given 24 hr before 0.2 mg 1,3-bis(2-chloroethyl)-1-nitrosourea.

Spleen colony assays showed that the survivors harbored viable leukemic cells for a number of days following treatment. Nevertheless, with the most effective regimen, about 75% of the survivors appeared healthy and had no detectable leukemic cells at the end of the 28-day period of observation. The survivors were resistant to further rechallenge with 106 leukemic cells, a dose that caused fatal leukemia by Day 6 in all untreated controls. About 25% of the surviving mice became paralyzed and died 4 to 6 weeks after treatment, with leukemic cells assayable in their femoral marrow and widespread leukemic involvement of their central nervous system.

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This work was supported by USPHS Grants AI 10622 and AM 05611; Grants CA 14656 and 1P02CA13053 from the National Cancer Institute; and a grant from the John A. Hartford Foundation.

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