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New synergistic combinations of differentiation inducing agents in the treatment of acute myeloid leukaemia

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Summary

Differentiation inducing agents in double and triple combinations can induce differentiation in primary culture of more than 80% of blast cells from some AML patients. In the present study, the interactions between these differentiating agents have been analysed using Berenbaum's general algebraic solution and three new, potentially clinically useful synergistic combinations: have been identified all trans retinoic acid (RA) + hexamethylene bisacetamide (HMBA), cytosine arabinoside (Ara-C) + HMBA and RA + Ara-C + HMBA.

A measure of the effectiveness of these combinations was that the doses of Ara-C and HMBA required to induce 50% differentiation were decreased about 10-fold and 5-fold, respectively, in combination with 1 μM RA.

The new synergistic combinations are important not only to limit toxicity but also because multiple drug combinations may better overcome the inherent molecular heterogeneity of the differentiation defect in AML patients. They warrant clinical trial in AML patients who are either unsuitable for or are unresponsive to conventional cytotoxic chemotherapy.

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  1. H. T. Hassan

    Present address: Institut für Pharmazie, Freie Universität Berlin, Kelchstraße 31, 1000, Berlin 41, Federal Republic of Germany

Authors and Affiliations

  1. Department of Haematology, Medical Research Institute, University of Alexandria, Alexandria, Egypt

    H. T. Hassan, L. E. Zyada & M. H. Ragab

  2. Department of Haematology, University of Cambridge Clinical School, Cambridge, England

    H. T. Hassan & J. K. H. Rees

Authors
  1. H. T. Hassan
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  2. L. E. Zyada
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  3. M. H. Ragab
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  4. J. K. H. Rees
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Hassan, H.T., Zyada, L.E., Ragab, M.H. et al. New synergistic combinations of differentiation inducing agents in the treatment of acute myeloid leukaemia. Eur J Clin Pharmacol 41, 531–536 (1991). https://doi.org/10.1007/BF00314980

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  • DOI: https://doi.org/10.1007/BF00314980

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