Chemotherapy of autochthonous myeloid leukemias (Chloroleukemias) in Wistar rats

Abstract

After injection of 15 mg/kg ethylnitrosourea (ENU) weekly for 15 weeks to adult male Wistar rats (total dose: 225 mg/kg) about 10% of the animals developed myeloid leukemias (chloroleukemias), which resemble the chronic myeloid leukemia in man (CML) (peripheral blood picture, tissue infiltration, chronic course as compared to immature-cell rat leukemias). Monotherapy with busulfan effected no remissions. The median survival time after daily treatment with busulfan was 29.5 days (range: 7-70); it was significantly shorter than that of untreated controls (median: 47.5 days, range: 22-81). After weekly application of 20 mg/kg and 50 mg/kg Cyclophosphamide the median survival time increased to 69.5 (range: 26-114) and 61.5 (range: 20-92) days, respectively. Rate and duration of remissions after repeated weekly single doses of cyclophosphamide were positively correlated with the increase in single dose; the high dose-intermittent treatment with 50 mg/kg CPA/week yielded complete remissions in all treated animals. Despite these remissions however, no significant increase in survival time could be observed in comparison with untreated controls. The comparability of autochthonous chloroleukemias in the rat with human CML is discussed.