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Journal of Cancer Research and Clinical Oncology

Published in:

01-02-2009 | Original Paper

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

Authors: M. Schmidt-Hieber, A. Busse, B. Reufi, W. Knauf, E. Thiel, I. W. Blau

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2009

Abstract

Purpose

We investigated the in vitro toxicity of bendamustine and fludarabine to hematopoietic progenitors and stem cells from healthy donors.

Methods

Clonogenic agar colony assays, non-clonogenic long-term liquid cultures (LTC) and apoptosis assays were used to assess the cytotoxicity of both the agents.

Results

Total colony-forming units (CFU) were more sensitive to fludarabine than to bendamustine in agar colony assays (IC₅₀ 0.7 μM/L and 8.5 μM/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.

Conclusions

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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Title: Bendamustine, but not fludarabine, exhibits a low stem cell toxicity in vitro
Authors: M. Schmidt-Hieber
A. Busse
B. Reufi
W. Knauf
E. Thiel
I. W. Blau
Publication date: 01-02-2009
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 2/2009
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-008-0453-8

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