Bendamustine, but not fludarabine, exhibits a low stem cell toxicity in vitro.

Journal of Cancer Research and Clinical Oncology
M Schmidt-HieberI W Blau

Abstract

We investigated the in vitro toxicity of bendamustine and fludarabine to hematopoietic progenitors and stem cells from healthy donors. Clonogenic agar colony assays, non-clonogenic long-term liquid cultures (LTC) and apoptosis assays were used to assess the cytotoxicity of both the agents. Total colony-forming units (CFU) were more sensitive to fludarabine than to bendamustine in agar colony assays (IC(50) 0.7 microM/L and 8.5 microM/L, respectively). Using the Bliss independence model and combining the two agents yielded additive inhibition of progenitors. Non-clonogenic assays, including LTC and an apoptosis assay detecting activated caspases showed that stem cells are characterized by low sensitivity to bendamustine. In contrast, fludarabine strongly inhibited the viability and growth of stem cells in LTC. Our data show that bendamustine is characterized by lower in vitro toxicity to hematopoietic progenitors and stem cells than fludarabine and might thus be preferable in regimens prior to stem cells apheresis.

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Citations

Jul 26, 2012·Blood Cancer Journal·M KaiserC D Baldus
Jan 1, 2009·Cancer Management and Research·Ibrahim T AldossPhilip J Bierman
Jul 14, 2011·Investigational New Drugs·Martin Schmidt-HieberIgor Wolfgang Blau
Jul 16, 2009·Leukemia & Lymphoma·Julie M VoseJohn Dipersio
Jun 6, 2012·Expert Opinion on Pharmacotherapy·Julie Elizabeth Chang, Brad Steven Kahl
Jun 11, 2011·Best Practice & Research. Clinical Haematology·Emmanuel Bachy, Gilles Salles
Oct 1, 2010·Advanced Materials·Matthias P Lutolf, Helen M Blau
Apr 18, 2013·Nature Reviews. Clinical Oncology·Stephane Doucet, Leo I Gordon
May 22, 2010·HEC Forum : an Interdisciplinary Journal on Hospitals' Ethical and Legal Issues·Roberta M BerryLeslie E Wolf

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