In vitro improvement of chlorambucil-induced cytotoxicity by deflazacort and 6-methylprednisolone in B-cell chronic lymphocytic leukaemia.
We examined whether CLL cell chemosensitivity to in vitro exposure to chlorambucil (CLB) might be improved by the presence of deflazacort (DFZ) 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 11 samples, respectively. The CBL-LD50 mean values were significantly reduced 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 observed 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 interactions were observed among CLB-PDN dose combinations, while analogous number of additive interactions were detected. At concentrations of CLB x1 microgram/ml the phenomenon of synergism, regardless of the steroid concentration, did occur more frequently. On the other hand, a more elevated number of antagonistic interactions were counted at CLB 100 micrograms/ ml. In conclusion, both DFZ and PDN synergize in vitro with CLB, especially at low concentrations of the alkylating agent.
Morabito
F
F
Hematology-Oncology Department, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. sp00404@relay.it.net
Callea
I
I
Irrera
G
G
Cartisano
G
G
Dattola
A
A
Rodinò
A
A
Brugiatelli
M
M
D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002699:Chlorambucil / Q000627:therapeutic use* / Q000633:toxicity; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D007928:Lethal Dose 50; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008775:Methylprednisolone / Q000494:pharmacology*; D011282:Pregnenediones / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D018906:Antineoplastic Agents, Alkylating; D011282:Pregnenediones; D002699:Chlorambucil; C021988:deflazacort; D008775:Methylprednisolone