THE EFFECTS OF 13-CIS RETINOIC ACID AND INTERFERON-ALPHA IN CHRONIC MYELOGENOUS LEUKEMIA-CELLS IN-VIVO IN PATIENTS

The effects of the administration of a 3-day course of 13-cis retinoic acid in combination with interferon a [RA/IFN] on the leukemia cells was measured in vivo in 43 patients with chronic myelogenous leukemia. The administration of RA/IFN was associated with a significant fall i n the white blood cell count of patients with chronic-phase disease an d with a fall in the percentage S-phase cells in CML patients regardle ss of the stage of their leukemia. In two thirds of the patients studi ed the administration of RA/IFN was also associated with an increase i n marrow apoptosis. The cytokine combination also suppressed bcl-2 and myc expression in a minority of patients and such expression appears to be associated with response to a treatment regimen which includes R A/IFN. These studies are the first to directly assess the effects of t he combination of RA/IFN on chronic myelogenous leukemia cells in vivo in patients. These effects, if seen in other malignant diseases, coul d account for the therapeutic benefit which has been associated with t he administration of this combination of biological agents to patients with malignant disease. (C) 1997 Elsevier Science Ltd. All rights res erved.