Sequential vincristine, arabinosylcytosine and adriamycin in acute leukemia: Cytologic and cytokinetic studies

Cytokinetic and cytocidal effects exerted on peripheral blood blasts by sequential administration of vincristine (VCR) 2 mg on day 1, arabinosylcytosine (Ara-c) 50-60 mg/m ²/12 hr from day 2-4), and adriamycin (ADM, Farmitalia, Milan, Italy, 40-60 mg/m ² on day 5) have been examined in 22 courses of treatment performed on 12 patients with nonlymphoblastic and in 4 with lymphoblastic acute leukemia. In 4 patients, the bone marrow blasts were examined before and also after VCR-Ara-c administration. In vitro tritiated thymidine autoradiography and propidium iodide-DNA flow cytometry were employed for kinetic studies. Blasts disappeared from blood with a median half time of 35 hr. After VCR-Ara-c administration, a significant increase in labeling index (LI) and in the aliquot of cells with DNA content between the diploid (2n) and the tetraploid (4n) values was observed in 80% of the courses in peripheral blood blasts and in all courses in bone marrow blasts. The median grain count over the labeled nuclei was decreased, and the 4n cell percentage and the bone marrow blast mitotic index did not increase. These findings suggest that the increase in the S phase fraction of blast population is due to cell synchronization. Increase in the S phase appears to heighten the cytocidal effect of ADM. The aliquot of the blasts cleared from blood after ADM were in fact related directly to the degree of labeling index increase observed during the previous administration of VCR and Ara-c.