In vitro drug testing in patients with acute leukemia with incubations mimicking in vivo intracellular drug concentrations.

European Journal of Haematology
U TidefeltC Paul

Abstract

The differential staining cytotoxicity (DiSC) assay was evaluated as a predictive test for response to therapy in patients with acute non-lymphoblastic leukemia. Incubations were designed in such a way that the intracellular concentrations of cytostatic drugs in vitro paralleled those in vivo. Leukemic cells were isolated from 53 patients with acute non-lymphocytic leukemia. 13 of these patients died early due to supportive care failure and were not evaluable for the predictive drug testing. Of the remaining 40 patients, 25 entered a complete remission (CR) and 15 had a resistant disease (RD). According to the patients randomization to therapy the cells were incubated with anthracyclines and Ara-C separately and in combination. After 4 days of culturing in liquid medium the in vitro cytotoxicity was determined by dye exclusion according to Weisenthal. The cytotoxic effect in vitro was significantly higher on cells from patients who achieved a CR compared to patients with RD after incubations with anthracyclines 0.2 mumol/l (p less than or equal to 0.005), Ara-C 0.5 mumol/l (p less than or equal to 0.05) and with the combination of anthracyclines with Ara-C (p less than or equal to 0.0005). The best predictive value was achieved...Continue Reading

References

Jan 1, 1979·Cancer Chemotherapy and Pharmacology·C PaulD Lockner
Jul 29, 1977·Science·A W Hamburger, S E Salmon
Jan 1, 1985·Hematological Oncology·M C BirdE D Gilby
Jan 1, 1980·Advances in Pharmacology and Chemotherapy·D D Von Hoff, L Weisenthal

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Citations

Jan 1, 1996·European Journal of Haematology·B Sundman-EngbergC Paul
Jun 14, 2003·Leukemia & Lymphoma·Lars MöllgårdUlf Tidefelt
May 27, 2003·Therapeutic Drug Monitoring·Kerstin Jönsson-VidesäterChrister Paul
Jan 1, 1994·Annals of Hematology·A J VeermanR Pieters
Oct 26, 2007·Cancer Chemotherapy and Pharmacology·Lars MöllgårdSören Lehmann
Jan 1, 1997·Critical Reviews in Oncology/hematology·R PietersA J Veerman
Apr 1, 1993·Leukemia Research·B Sundman-EngbergC Paul

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