LIPOSOMAL VINCRISTINE FOR THE TREATMENT OF HUMAN ACUTE LYMPHOBLASTIC-LEUKEMIA IN SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE

Non-obese diabetic NOD/SCID mice have been used to grow human leukaemi a as a systemic disease. The animals were inoculated with leukaemic ce lls obtained from a 36-year-old male with early B-cell precursor acute lymphoblastic leukaemia and on day 15 were given the first of three w eekly injections of 1 mg/kg vincristine or equimolar liposomal vincris tine. The development of leukaemia in the mice was monitored by taking weekly blood samples and measuring the cell content by flow cytometry . The median time to 50% human cells in the peripheral blood of mice t reated with free vincristine was 41 d from the start of treatment comp ared with 49 d for mice treated with liposomal vincristine (P < 0.01). The median day of death for mice treated with free vincristine was 47 d from the start of treatment and 57 d for mice receiving liposomal v incristine (P < 0.01), thus providing a 21% increase in lifespan for a nimals treated with the liposomal preparation. There was slightly grea ter weight loss in mice treated with free vincristine than those given liposomal vincristine. Measurement of in vitro colony forming bone ma rrow progenitor cells in similarly treated, tumour-free mice, showed n o difference in progenitor cell survival between mice that received ei ther type of vincristine. We conclude that encapsulating vincristine i n liposomes improves the therapeutic index of this drug measured in mi ce bearing human leukaemia. This may lead to use of the drug in conven tional combination chemotherapy with greater safety or, in this settin g, at higher dosage.