Decreased retention of vinca alkaloids in chronic lymphatic leukemia cells from refractory patients

Uptake and retention of vincristine (VCR), vinblastine (VB), and vindesine (VD) in isolated mononuclear cells from six healthy donors and in leukemic cells from 12 patients with chronic lymphatic leukemia (CLL) were studied: Three patients responded to VCR-containing regimens, whereas 4 patients were or became refractory and five patients did not receive VCR. Incubation of leukemic or normal cells with 1 microgram/ml vinca alkaloid for 1-24 h showed a steady state level after 1-2 h. Normal cells both took up and retained significantly more drug than those from patients, both responding and refractory. Cells from VCR-refractory patients had a significantly (P less than 0.01) lower drug retention than those from patients responding to or not receiving VCR. In contrast, the difference in uptake was not statistically significant.