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Comparative Cytotoxicity of Various Drug Combinations for Human Leukemic Cells and Normal Hematopoietic Precursors¹

Hematology/Lymphoma Service, Department of Medicine [T. T. C., S. C. G., B. C.] and Pharmacology Laboratory [T-C. C.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and the Department of Pharmacology, Johns Hopkins University Oncology Center, Baltimore, Maryland 21205 [M. C.]

The development of suitable methods for purging the malignant cells contaminating the bone marrow of patients with cancer may offer a better chance of success for autologous bone marrow transplantation. In this paper, we further describe our efforts at purging acute myelogenous leukemia cells. HL-60, a promyelocytic leukemia cell line, was used as a model. 4-Hydroperoxycyclophosphamide (4-HC), VP-16-213 (VP-16), and Adriamycin were used alone or in combination to develop the best method to purge HL-60 cells. The cytotoxicity of 29.2 µg/ml (100 µM) of 4-HC was 99.8 ± 0.12% (SD) on HL-60 cells and 82.5% on colony forming units-granulocyte, macrophage. Ninety-nine % of HL-60 cells and 72.7% of colony forming units-granulocyte, macrophage were inhibited by VP-16 at a concentration of 25 µg/ml (42.5 µM). The cytotoxicity of 1.5 µg/ml (2.76 µM) of Adriamycin on HL-60 cells was 98.6 ± 0.8% and inhibited colony forming units-granulocyte, macrophage by 50.8%. The cytotoxicity and interactions of any two drug combinations at different combination ratios and the different effect levels were quantitatively determined by median effect plot and the multiple drug effect equation (T-C. Chou and P. Talalay. Adv. Enzyme Regul. 22: 27–55, 1984). The combination of 4-HC and VP-16 at a 4-HC:VP-16 drug ratio of 1:0.342 was found to be the best for selective toxicity towards HL-60 cells and was superior to the 4-HC-Adriamycin or VP-16 Adriamycin combination for usefulness in purging bone marrow.

¹ This work was supported in part by the American Cancer Society and by NIH Grants CA-19117, and CA-27569, and CA-18856.

² Visiting fellow at Memorial Sloan-Kettering Cancer Center supported by Chung-Ho Memorial Hospital, Kaohsiung Medical College, Kaohsiung, Taiwan, Republic of China.

³ American Cancer Society Clinical Oncology Career Development Awardee. To whom requests for reprints should be addressed, at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 2/19/86. Revised 7/16/86. Accepted 9/25/86.

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