Abstract | BACKGROUND AND OBJECTIVES: DESIGN AND METHODS: 2 lines (DOHH-2, WSU-NHL) and mononuclear cells (MNC) from patients with leukemic low-grade B- non-Hodgkin's lymphoma (NHL) (n=10), T-NHL (n=7) and chronic lymphocytic leukemia (CLL) (n=12). Apoptosis (7-AAD), depolarization of mitochondrial membrane potential (MMP, JC-1), caspase-3-activity (FIENA) and cell proliferation (XTT/WST-1) were determined. Several incubation times and drug dosages (for IC(30/50/75/90)) were studied. Synergistic, additive or antagonistic effects were calculated by a median plot effect and the combination index (CI) method. RESULTS: In general, combinations of bendamustine with mitoxantrone or doxorubicin resulted in antagonistic effects in the tested cell lines and the MNC from the patients. CI-calculation failed in these cases since there was not a sufficient dose response. On the other hand, the combination of bendamustine with 2-CdA showed synergistic in vitro activity on the tested cell lines, neoplastic lymphocytes from patients with peripheral T-cell lymphomas and partially on MNC from patients with CLL and B-NHL. The antagonism of the combination of bendamustine and anthracyclines appeared to be due to inhibition of depolarization of mitochondrial-membrane potential and caspase-3-activity during apoptosis of the studied cell lines. INTERPRETATION AND CONCLUSIONS: In conclusion, our results suggest that schedules using combinations of bendamustine and anthracyclines should not be recommended for the treatment of low-grade NHL, whereas bendamustine combined with 2-CdA could be considered for the development of future treatment strategies.
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Authors | K U Chow, S Boehrer, K Geduldig, A Krapohl, D Hoelzer, P S Mitrou, E Weidmann |
Journal | Haematologica
(Haematologica)
Vol. 86
Issue 5
Pg. 485-93
(May 2001)
ISSN: 0390-6078 [Print] Italy |
PMID | 11410411
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Nitrogen Mustard Compounds
- Bendamustine Hydrochloride
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Bendamustine Hydrochloride
- Drug Interactions
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell
(drug therapy, pathology)
- Lymphoma, Non-Hodgkin
(drug therapy, pathology)
- Nitrogen Mustard Compounds
(pharmacology, therapeutic use)
- Tumor Cells, Cultured
(drug effects)
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