In vitro reappearance of myeloid progenitors killed by mafosfamide

Cyclophosphamide derivatives active in vitro, such as mafosfamide, are potentially capable of reducing the number of leukemic cells remaining in marrow explanted for autografting. Although this treatment kills nearly all the committed hemopoietic progenitors, it does not prevent the reinstatement of hemopoiesis after chemoradiotherapy. This points to the persistence of more immature hemopoietic progenitors not detectable with current semi-solid culture techniques and resistant to cytotoxic treatment. Treatment of normal marrow with 80-140 micrograms/ml mafosfamide is followed in medium-term cultures by a gradual and dose-dependent reduction in total cellularity, whereas granulomonocyte progenitors (CFU-GM), virtually absent at the start of the culture, progressively reappear. The quantity of progenitors present after day 14 in liquid culture is, however, less in the treated marrows than in the controls, and the reappearance of CFU-GM is inversely related to the mafosfamide dose. In addition, the recovery of the more immature (day-14) CFU-GM is greater than that of the more mature (day 7) CFU-GM.