Drug effect in acute leukemia

Abstract

The in vivo therapeutic effect of vincristine, cytosine arabinoside, and corticosteroids on leukemic blast cells in the bone marrow was evaluated. 24 studies were done in 21 children with acute leukemia. 19 children had acute lymphoblastic leukemia, and two children had acute myeloblastic leukemia. Direct cytotoxicity or lysis of blast cells after drug administration was looked for by serial measurements of the volume of marrow buffy coat. Changes in proliferative capacity were evaluated by serial measurements of number of cells in mitosis and the per cent of cells in deoxyribonucleic acid (DNA) synthesis, as indicated by tritiated thymidine incorporation. Corticosteroid administration caused lysis of leukemic blast cells. Each drug affected the proliferative capacity of the leukemic cells by an action at a different part of the mitotic cycle. Corticosteroids suppressed the entry of cells into DNA synthesis. Vincristine arrested cells in mitosis. Cytosine arabinoside inhibited DNA synthesis. After the inhibitory effect of cytosine arabinoside, an increased number of cells began to synthesize DNA, a phenomenon indicating that partial synchronization of the mitotic cycle had been achieved in the leukemic cell population. The action of these drugs at different parts of the mitotic cycle might be important in designing treatment regimens where in two or more of these drugs are used.