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High activity and incomplete cross resistance of nucleoside analogues cladribine and fludarabine versus ara-C on leukemic cells from patients with AML
Löfgren, C., Department of Clinical Hematology, Karolinska University Hospital, Stockholm, Sweden, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, Hematology Center Karolinska, M 54 Huddinge, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology .
Department of Clinical Hematology, Karolinska University Hospital, Stockholm, Sweden, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
2005 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 27, no 5, 641-646 p.Article in journal (Refereed) Published
Abstract [en]

The in vitro activity and cross-resistance pattern of the purine analogues cladribine and fludarabine and the pyrimidine analogue cytarabine on leukemic cells from 170 patients with AML was evaluated using a bioluminescence assay. In in vivo mimicking concentrations, cladribine (50 nmol/L) and fludarabine (2 µmol/L) were more cytotoxic than cytarabine (0.5 µmol/L). The cytotoxic effect of fludarabine correlated weakly to cytarabine (r = 0.37, P < 0.001). The cytotoxic effect of cladribine correlated better to cytarabine (r = 0.49, P = 0.0002) but best to fludarabine (r = 0.82, P < 0.001). There was an absence of correlation between either cladribine or fludarabine and daunorubicin (0.2 µmol/L). Of 45 highly Ara-C-resistant samples, cladribine exerted high or intermediate effect in 54% and fludarabine in 52%. These in vitro data indicate that cladribine and fludarabine are active drugs in the treatment of AML. The cross resistance to cytarabine was not complete, and the drugs can be valuable either as alternatives to Ara-C or in combination therapy for treatment of leukemia resistant to standard therapy. Copyright © 2005 by Lippincott Williams & Wilkins.

Place, publisher, year, edition, pages
2005. Vol. 27, no 5, 641-646 p.
Keyword [en]
Acute myeloid leukemia, Cladribine, Cytarabine, Cytotoxicity, Fludarabine, In vitro chemosensitivity
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-50414DOI: 10.1097/01.ftd.0000175157.94192.dcOAI: oai:DiVA.org:liu-50414DiVA: diva2:271310
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12

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