Hassan H T, Zyada L E, Ragab M H, Rees J K
Department of Haematology, University of Alexandria, Egypt.
Eur J Clin Pharmacol. 1991;41(6):531-6. doi: 10.1007/BF00314980.
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 microM 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.
双重和三重组合的分化诱导剂可诱导部分急性髓系白血病（AML）患者原代培养中80%以上的原始细胞发生分化。在本研究中，利用贝伦鲍姆的通用代数解法分析了这些分化诱导剂之间的相互作用，并确定了三种新的、可能具有临床应用价值的协同组合：全反式维甲酸（RA）+六甲撑双乙酰胺（HMBA）、阿糖胞苷（Ara-C）+HMBA以及RA+Ara-C+HMBA。这些组合有效性的一个衡量标准是，与1微摩尔RA联合使用时，诱导50%分化所需的Ara-C和HMBA剂量分别降低了约10倍和5倍。新的协同组合不仅对于限制毒性很重要，而且因为多种药物组合可能更好地克服AML患者分化缺陷所固有的分子异质性。它们值得在不适合或对传统细胞毒性化疗无反应的AML患者中进行临床试验。
