Perturbation of Generation Cycle of Human Leukemic Blast Cells by Cytostatic Therapy In Vivo: Effect of Corticosteroids

The in vivo cell cycle effects of intensive short-term corticosteroid treatment on bone marrow lymphoblasts have been studied in five patients with acute lymphoblastic leukemia. In repeated bone marrow samples, the following parameters were determined: mitotic index, stathmokinetic index after vincristine, ³H-thymidine labeling index and single cell DNA content. It is concluded that prednisone has a general destructive effect both on actively proliferating and on quiescent leukemic lymphoblasts. Besides, prednisone has an additional effect on proliferating lymphoblasts which manifests itself by a decreased influx from G₁ phase into DNA synthesis phase. From the present data it cannot be decided whether this is due to a depopulation of the G₁ pool or results from an arrest of cells in G₁. No evidence has been found for selective cell death during DNA synthesis. Some implications of this cytokinetic perturbation for therapeutic combination of corticosteroids with methotrexate and vincristine are discussed.