LOXORIBINE AFFECTS FLUDARABINE ACTIVITY ON FRESHLY ISOLATED B-CHRONICLYMPHOCYTIC-LEUKEMIA CELLS

Purine analogues like fludarabine have been shown to be superior to co nventional therapy for B-cell chronic lymphocytic leukemia (B-CLL). In order to improve the activity of fludarabine, we tested its combinati on with loxoribine, a guanine ribonucleotide derivative, known to enha nce the sensitivity of B-CLL cells to cytotoxic drugs. B-CLL cells fro m 6 patients were studied; co-incubation with loxoribine 100 mu M incr eased the activity of fludarabine by 12% to 48%, as demonstrated by XT T colorimetric assay; while 1000 mu M loxoribine exerted a protective effect. Accordingly, fludarabine-induced apoptosis was enhanced by the addition of loxoribine 100 mu M (39% increase). These results indicat e that the combination of loxoribine and fludarabine could be of inter est in B-CLL.