In vitro chemo-sensitivity of B-chronic lymphocytic leukaemia to ara-G

Abstract 

In vitro sensitivity to ara-G of peripheral blood B-CLL lymphocytes from 23 patients was assessed using the flow cytometric TdT assay. All patients had typical B-CLL, according to immunophenotype and morphology, and none had received treatment within 1 year of testing. A wide range of spontaneous apoptosis was recorded. Exposure of the cells to a concentration of ara-G, comparable to plasma levels achieved in a phase I trial, produced significant increases in the rate of apoptosis in 21 out of 23 patients. Prior treatment, stage or lymphocyte doubling time did not influence the effect of ara-G. Ten patients’ samples tested, in parallel, for sensitivity to fludarabine demonstrated a good correlation of response to both drugs. This in vitro evidence of activity against B-CLL suggests that the spectrum of clinically useful action may be broader than previously demonstrated.

Keywords:  CLL, Chemosensitivity, Ara-G, Purine analogues

Abbreviations:  Ara-G, guanine arabinoside, B-CLL, B-chronic lymphocytic leukaemia, CdA, 2-chlorodeoxyadenosine, PB, peripheral blood, TdT, terminal deoxynucleotidyl transferase