Effects of cytosine arabinoside on DNA synthesis as predictor for acute myelocytic leukemia (AML) patients' response to chemotherapy

Abstract

Bone marrow cells from 25 AML patients were exposed to cytosine arabinoside and the effects of the drug on the incorporation of ³H-TdR by the cells were measured and compared to the response of the patients to antileukemia chemotherapy with ara C and an anthracycline. The majority of the leukemic cells of the patients in whom bone marrow hypoplasia was not achieved as a result of treatment were classified as resistant to the drugs administered. Incubation with 0.3 μg/ml ara C inhibited DNA synthesis in 11 of 12 resistant patients by 20–95%. Exposure to 3.0 μg/ml drug inhibited the incorporation of ³H-TdR in 10 of 11 resistant patients by 38–98%. The in vivo resistance of the leukemic cells to ara C was not reflected by the in vitro response of the synthesis of DNA by these cells to ara C. The effects of ara C on DNA synthesis were also not correlated to the drug's effects on the clonogenic cells in 21 bone marrow specimens. We conclude that the effects of ara C on DNA synthesis are not predictive to a patient's response to therapy, nor do they reflect the cytocidal effects of the drug on the clonogenic cells.