A cellular analysis of long-term haematopoietic damage in mice after repeated treatment with cyclophosphamide

Following repeated treatment of mice with cyclophosphamide (5 X 200 mg/kg) it was found that slight, but significant, residual marrow damage persisted for at least half the lifespan of the animals. This long-term damage occurred despite preferential sparing of those multi-potential haematopoietic cells (CFU-S) that had a high self-renewal capacity after each step of the multistep regimen and despite a smaller CFU-S kill after each successive dose. The damage was characterized by low mean numbers of CFU-S and stromal colony-forming cells (CFU-F) which were around 70% of control values. Examination of individual animals revealed that the majority had slightly subnormal numbers of CFU-S and CFU-F, with only a few suffering a more severe injury, including 8% of mice with clinical hypoplasia or myelodysplasia.