Kinetic response of human leukemic and lymphoma cells in vivo to combination chemotherapy using flow microfluorometry

Two patients with acute leukemia and one with a presumptive diagnosis of diffuse histiocytic lymphoma were treated with vinca alkaloids (vincristine or the new chemotherapeutic agent desacetyl vinblastine amide [vindesine]); two patients were also given prednisone and one received adriamycin. Kinetic responses of the tumor cells to treatment were measured by sampling bone marrow or peripheral blood prior to and at intervals after the administration of the drugs. Differential counts, mitotic and ³HTdR pulse-labeling indices, and the distribution of cells among the phases of the mitotic cycle by flow microfluorometry were determined. In the patient diagnosed as having lymphoma there was an initial increase in the mitotic index and in the percentage of S-phase cells, but these decreased after prednisone administration. The patient subsequently went into remission. Another patient (with acute myelomonocytic leukemia), who received vincristine together with prednisone and adriamycin, showed little apparent kinetic or clinical response to the treatment except for a small increase in the percentage of cells in G ₂ and a moderate decrease in the percentage of blast cells. Although his leukemic cells were affected by subsequent administration of cytosine arabinoside, remission was not achieved. The third patient, who had acute lymphoblastic leukemia and who had been treated extensively with other drugs prior to the present study, was given vindesine in a single iv injection. There was a transient increase in the mitotic index and a decrease in the percentage of S-phase cells, but the changes were not striking.