Residual marrow damage following therapy with cyclophosphamide

Studies were performed to determine the type of residual marrow damage which occurs after injecting mice with 200 mg/kg of cyclophosphamide every 2 weeks for 5 courses. Mice treated with cyclophosphamide, and controls injected with normal saline, were studied 6 weeks after the last injection. Complete blood counts, and total nuclear cell counts from femoral marrow revealed no differences between the 2 groups. The number of CFUs in the marrow of cyclophosphamide treated mice was slightly, but significantly, lower than of controls. Cyclophosphamide treated and control mice were then exposed to 300 rad, and the rate of marrow CFUs recovery was determined. That of cyclophosphamide treated mice was significantly slower than that of controls. Stromal function of marrows from cyclophosphamide treated mice was significantly impaired. Also, however, the proliferative potential of marrow CFUs of cyclophosphamide treated mice was modestly reduced relative to that of controls. We conclude that cyclophosphamide treatment of mice results in significant residual marrow damage, due primarily to "stromal" damage, but also to decrease in the proliferative potential of CFUs.