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.
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.