In vitro improvement of chlorambucil-induced cytotoxicity by deflazacort and 6-methylprednisolone in B-cell chronic lymphocytic leukaemia

Eur J Haematol. 1997 May;58(5):301-6. doi: 10.1111/j.1600-0609.1997.tb01675.x.

Abstract

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.

MeSH terms

  • Analysis of Variance
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Agents, Alkylating / toxicity
  • Apoptosis / drug effects
  • Chlorambucil / therapeutic use*
  • Chlorambucil / toxicity
  • Drug Interactions
  • Drug Synergism
  • Humans
  • Lethal Dose 50
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Methylprednisolone / pharmacology*
  • Pregnenediones / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Alkylating
  • Pregnenediones
  • Chlorambucil
  • deflazacort
  • Methylprednisolone