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


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.
Skribek
Henriette
H
Department of Microbiology, Tumor and Cell Biology and Center for Integrative Recognition in the Immune System, Karolinska Institute, Stockholm, Sweden.
Otvos
Rita
R
Flaberg
Emilie
E
Nagy
Noemi
N
Markasz
Laszlo
L
Eksborg
Staffan
S
Masszi
Tamas
T
Kozma
Andras
A
Adam
Emma
E
Miseta
Attila
A
Klein
Eva
E
Szekely
Laszlo
L
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D016000:Cluster Analysis; D003630:Daunorubicin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D011239:Prednisolone / Q000008:administration & dosage
D015251:Epirubicin; D004317:Doxorubicin; D011239:Prednisolone; D003630:Daunorubicin