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


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.
Schmidt-Hieber
M
M
Medizinische Klinik III (Hämatologie, Onkologie und Transfusionsmedizin), Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. martin.schmidt-hieber@charite.de
Busse
A
A
Reufi
B
B
Knauf
W
W
Thiel
E
E
Blau
I W
IW
D000970:Antineoplastic Agents / Q000633:toxicity*; D000069461:Bendamustine Hydrochloride; D001781:Blood Component Removal / Q000379:methods; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D009588:Nitrogen Mustard Compounds / Q000633:toxicity*; D012016:Reference Values; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000633:toxicity
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D016179:Granulocyte Colony-Stimulating Factor; D000069461:Bendamustine Hydrochloride; D014740:Vidarabine; C024352:fludarabine