Kinetics of normal hemopoietic stem cells during leukemia growth before and after induction of a complete remission. Studies in a rat model for acute myelocytic leukemia (BNML).

During the invasion of leukemic cells of the rat acute myelocytic leukemia model BNML in the bone marrow, the number of normal bone marrow stem cells (CFU-S) decreased while simultaneously an increase of CFU-S in the leukemic spleen was observed. A small reduction in the tumor load by low dose cyclophosphamide treatment (10 mg/kg) caused a temporary CFU-S recovery in the bone marrow. After a therapeutic dose of cyclophosphamide (100 mg/kg), the CFU-S numbers in femur and spleen decreased to low levels but they rapidly increased immediately thereafter. In the spleen, however, the CFU-S increase halted when femoral CFU-S numbers reached normal levels. Splenectomy following cyclophosphamide treatment revealed that the splenic CFU-S population does not play a role in regeneration of hemopoiesis. During the subsequent leukemia relapse, CFU-S in the femur decreased again while spleen CFU-S tended to rise. It is concluded that the bone marrow CFU-S, which survive both the leukemia and the remission-induction treatment, and not the migrated, extramedullary localized stem cells are the major source for the restoration of normal hemopoiesis.