Lithium and hematopoietic toxicity. III. In vivo recovery of hematopoiesis following single-dose administration of cyclophosphamide.

Studies are described that demonstrate the ability of lithium (Li) to enhance total peripheral blood neutrophil, platelet and stem cell (CFU-S, CFU-MIX, CFU-GM and CFU-MEG) populations from mice administered cyclophosphamide (CTX). Mice were preinjected on each of 3 consecutive days with ultrapure lithium carbonate (Li2CO3, 35 micrograms/kg b.w.) before receiving CTX (200 mg/kg, b.w.). Control groups were preinjected with phosphate-buffered saline (PBS) before receiving CTX. On days 1, 5, 7, 14, 21, and 28 following CTX, 3 mice from each group were sacrificed. Peripheral blood was obtained and examined for their packed red cell volume, white blood cell differential and platelet counts. Bone marrow and spleen cells were harvested and assayed for their stem cell content (CFU-S, CFU-MIX, CFU-GM, and CFU-MEG). Mice receiving Li prior to CTX did not develop thrombocytopenia and their absolute granulocyte counts recovered more rapidly when compared to CTX-PBS controls. Li-CTX bone marrow CFU-S and CFU-MIX were not as severely depressed when compared to the CTX-PBS controls. Li-CTX splenic-derived CFU-GM and CFU-MEG were increased significantly when compared to CTX-PBS controls and their rate of recovery was greater than that observed from bone marrow. These results demonstrate and confirm the capability of Li to accelerate hematopoietic recovery following the use of agents known to suppress hematopoiesis.