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

Abstract

Abstract 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.