title: 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.
  
  
  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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology and Center for Integrative Recognition in the Immune System, Karolinska Institute, Stockholm, Sweden.
authors.forename: Henriette
authors.initials: H
authors.lastname: Skribek
authors.forename: Rita
authors.initials: R
authors.lastname: Otvos
authors.forename: Emilie
authors.initials: E
authors.lastname: Flaberg
authors.forename: Noemi
authors.initials: N
authors.lastname: Nagy
authors.forename: Laszlo
authors.initials: L
authors.lastname: Markasz
authors.forename: Staffan
authors.initials: S
authors.lastname: Eksborg
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.forename: Andras
authors.initials: A
authors.lastname: Kozma
authors.forename: Emma
authors.initials: E
authors.lastname: Adam
authors.forename: Attila
authors.initials: A
authors.lastname: Miseta
authors.forename: Eva
authors.initials: E
authors.lastname: Klein
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szekely
mesh_terms: 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
chemical_list: D015251:Epirubicin; D004317:Doxorubicin; D011239:Prednisolone; D003630:Daunorubicin