Cell differentiation and therapeutic effect of low doses of cytosine arabinoside in human myeloid leukemia.
Bone marrow cells from 2 patients over 60 years of age with acute myeloblastic (AML) or monoblastic (AMoL) leukemia were cultured in the presence of a low dose of cytosine arabinoside. In the cells from the AML patient this treatment induced differentiation to metamyelocytes and a decrease in the number of blasts, so that there was an 11-fold increase in the ratio of differentiated myeloid cells to blasts. In the patient with AMoL there was differentiation to monocytes and macrophages and only a 3-fold increase in the ratio of differentiated myeloid cells to blasts. In the latter patient actinomycin D was a more potent inducer of differentiation than cytosine arabinoside, daunomycin was similar to cytosine arabinoside and adriamycin showed the lowest response. Four courses of low dose treatment with cytosine arabinoside produced remission in the patient with AML and in another patient with AMoL whose cells were not tested in culture. No remission was induced by this low dose treatment in the patient with AMoL whose cells showed only a small decrease in blast cells in culture with cytosine arabinoside. It is suggested that prescreening for effective compounds in patients with myeloid leukemias and the use of low dose therapy can be of help in obtaining remission without serious side effects. This could be especially useful in patients where there may be severe toxic effects after high dose chemotherapy.
D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male
D003561:Cytarabine