Synchronization with phase-specific agents in leukemia and correlation with clinical response to chemotherapy

Mitotic indices, labeling indices (LI), and tritiated thymidine incorporation into DNA of marrow cells were conducted in patients with leukemia to determine if correlations existed between kinetic measurements, clinical features, and response to chemotherapy. Higher proliferative activity was observed in chronic granulocytic leukemia (CGL) and blastic phase of CGL than in acute leukemia. In acute myelogenous leukemia there was no correlation with various clinical features studied. Those patients demonstrating greater than 60% reduction in circulating leukemia cells within 7 days had a higher initial LI than those with less than 60% reduction. Cytosine arabinoside, methotrexate, and hydroxyurea were investigated to determine their synchronizing capability; cytosine arabinoside and methotrexate were superior to hydroxyurea. In a cycle-sensitive schedule specifically designed to synchronize cells, responses occurred more frequently in patients who increased thier LI 48 hours after priming doses of cytosine arabinoside. In an intensive-chemotherapy schedule which produced more remissions than the cycle-sensitive schedule, there was no relationship between initial kinetic measurements and response. Kinetic values increased as patients achieved remissions.