Loxoribine affects fludarabine activity on freshly isolated B-chronic lymphocytic leukemia cells

Purine analogues like fludarabine have been shown to be superior to conventional therapy for B-cell chronic lymphocytic leukemia (B-CLL). In order to improve the activity of fludarabine, we tested its combination with loxoribine, a guanine ribonucleotide derivative, known to enhance the sensitivity of B-CLL cells to cytotoxic drugs. B-CLL cells from 6 patients were studied; co-incubation with loxoribine 100 mu M increased the activity of fludarabine by 12% to 48%, as demonstrated by XTT 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 indicate that the combination of loxoribine and fludarabine could be of interest in B-CLL.