IN-VITRO IMPROVEMENT OF CHLORAMBUCIL-INDUCED CYTOTOXICITY BY DEFLAZACORT AND 6-METHYLPREDNISOLONE IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA

We examined whether CLL cell chemosensitivity to in vitro exposure to chlorambucil (CLB) might be improved by the presence of deflazacort (D FZ) in comparison to 6-methylprednisolone (PDN). The PDN lethal dose ( LD)(50) values were low in 5 samples, intermediate in 4 and high in 7. Low intermediate and high DFZ-LD50 values were detected in 3, 2 and 1 1 samples, respectively. The CBL-LD50 mean values were significantly r educed at all PDN and at the 4 highest DFZ concentrations. However, a dose-response effect was seen only in the DFZ group. Both CLB-DFZ and CLB-PDN interactions were analysed in 16 samples at 25 different dose- combinations, resulting in 400 comparisons between expected and observ ed leukaemic cell survival (LCS) values for each group. In particular, 45.75% and 40% dose combinations were synergistic in CLB-DFZ and CLB- PDN groups, respectively. A relatively higher number of antagonistic i nteractions were observed among CLB-PDN dose combinations, while analo gous number of additive interactions were detected. At concentrations of CLB x1 mu g/ml the phenomenon of synergism, regardless of the stero id concentration, did occur more frequently. On the other hand, a more elevated number of antagonistic interactions were counted at CLB 100 mu g/ml. In conclusion, both DFZ and PDN synergize in vitro with CLB, especially at low concentrations of the alkylating agent.