In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia
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- 作者：Aleksandar Radujkovic (1)
Thomas Luft (1)
Peter Dreger (1)
Anthony D. Ho (1)
W. Jens Zeller (2)
Stefan Fruehauf (3)
Julian Topaly (4) - 关键词：CML ; Combination treatment ; Nilotinib ; Synergism ; Alkylating agents ; Conditioning
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：2014
- 出版时间：August 2014
- 年：2014
- 卷：74
- 期：2
- 页码：427-432
- 全文大小：381 KB
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21. Radujkovic A, Dreger P, Hegenbart U, Buss EC, Luft T, Ho AD, Fruehauf S, Topaly J (2014) Imatinib-supplemented myeloablative total-body irradiation/cyclophosphamide conditioning prior to allogeneic stem cell transplantation as consolidation treatment in patients with blast crisis of chronic myeloid leukemia. Eur J Haematol 92:546-49 CrossRef - 作者单位：Aleksandar Radujkovic (1)
Thomas Luft (1)
Peter Dreger (1)
Anthony D. Ho (1)
W. Jens Zeller (2)
Stefan Fruehauf (3)
Julian Topaly (4)
1. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
2. Research Group Pharmacology of Cancer Treatment, German Cancer Research Center, Heidelberg, Germany
3. Klinik fuer Haematologie und Onkologie, Palliativmedizin, Klinikum Bad Hersfeld, Bad Hersfeld, Germany
4. MVZ, Klinikum Osnabrueck, Am Finkenhuegel 1-, 49076, Osnabrueck, Germany - ISSN：1432-0843
文摘
Purpose The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Methods Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR–ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Results Treatment of imatinib-sensitive, BCR–ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI??1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI? Conclusions Our in vitro data warrant further investigation and may provide the basis for nilotinib-supplemented conditioning regimens for allo-SCT in advanced-phase CML.