Manipulation of the mitotic cycle in the treatment of acute myelogenous leukaemia.

A priming dose of cytosine arabinoside (Ara C) was given to 16 children and five adults with acute myelogenous leukaemia (AML) to synchronize leukaemia cells in the DNA synthesis (S) phase of the mitotic cycle. An infusion of this drug, which was continued for 12 h, was started at the time of partial synchronization and was repeated every 6-12 h until the bone marrow was very hypocellular. Complete remission was achieved in 12 of 16 children and in all adults. Two of the four children went into complete remission with the addition of two doses of daunorubicin or adriamycin. These results suggest that partial synchronization of cells in the S phase results in a therapeutic advanatage in the use of Ara C for induction of a remission of AML and that manipulation of the mitotic cycle, as monitored by kinetic studies, may be helpful in planning optimal schedules for drug administration.