In vitro activity of vinorelbine on human leukemia cells

Vinorelbine (VNR) is a semi-synthetic Vinca rosea alkaloid that has been em ployed both as a single agent and in combination, and has shown significant antitumor activity. As little is known about VNR activity on human leukemi a, we studied its in vitro cytotoxic effect on human leukemia cell lines (F LG 29.1, HL60, K562, Balm 4, CEM and Daudi) and on fresh leukemia cells fro m 28 patients: 2 acute myeloid leukemia (AML); 3 chronic myeloid leukemia i n blastic phase (CML-BP); 5 acute lymphoblastic leukemia (ALL); 18 B-chroni c lymphatic leukemia (B-CLL), employing the colorimetric INT assay and dete rmining the IC50. We observed that VNR exerts its cytotoxic activity on leukemic cell lines i n a dose-dependent fashion. The lymphoid cell lines appear more sensitive t han the myeloid ones to the VNR-dependent growth inhibition. A similar pattern was noticed for leukemia cells in primary cultures. VNR i s not effective on CML-BP cells, shows variable activity on the AML and ALL cells and is very effective against B-CLL cells. VNR inhibited the growth of fresh B-CLL cells from 15 of 18 patients, the IC50 doses ranging from 4 ng/ml to 83 mug/ml (doses coinciding with the plasma levels obtained in cli nics). These observations strongly suggest that VNR could be useful in clin ics for the treatment of B-CLL.