Chronic lymphoid leukemia cells are highly sensitive to the combination of prednisolone and daunorubicin, but much less to doxorubicin or epirubicin

Abstract

Objective: To generate a comprehensive map of the drug sensitivity of chronic lymphoid leukemia cells (CLL) using a newly developed in vitro drug-sensitivity assay based on automated evaluation of cell viability on single-cell level.

Materials and methods: Primary CLL cells from 77 patients were tested using automated digital fluorescence microscopy. The effect of 27 frequently used chemotherapeutic agents was measured in short-term fluorescence survival assay. To avoid typical in vitro artifacts such as growth factor depletion and oxidative damage, the cell were cultured in a novel, total human blood lysate-based medium (OmniSanguine) in order to preserve the composition of growth factor flora and redox conditions of the in vivo environment.

Results: CLL cells from different patients showed considerable heterogeneity in their drug-sensitivity patterns. This pattern was stable even after in vitro activation of cell proliferation. Half of the samples were sensitive to fludarabine and chlorambucil. Daunorubicin was the most potent drug. It was effective in 75 of 77 cases. In addition, daunorubicin and prednisolone showed a strong synergistic effect.

Conclusions: We suggest that the combination of low-dose daunorubicin and prednisolone might be an additional treatment option for therapy-resistant cases of CLL.