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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia.
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All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia.

机译：全反式维甲酸/ As2O3组合可在新诊断的急性早幼粒细胞白血病中获得高质量的缓解和生存。

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摘要

Both all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, As(2)O(3), and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RAR alpha (promyelocytic leukemia-retinoic acid receptor alpha) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high (> or =90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RAR alpha transcripts at CR decreased more significantly in combined therapy as compared with ATRA or As(2)O(3) mono-therapy (P < 0.01). This difference persisted after consolidation (P < 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed (P < 0.05) after a follow-up of 8-30 months (median: 18 months). Synergism of ATRA and As(2)O(3) on apoptosis and degradation of PML-RAR alpha oncoprotein might provide a plausible explanation for superior efficacy of combination therapy in clinic. In conclusion, the ATRA/As(2)O(3) combination for remission/maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival.
机译：全反式维甲酸（ATRA）和三氧化二砷（As（2）O（3））已被证明在急性早幼粒细胞白血病（APL）中获得高临床完全缓解（CR）率非常有效，但他们没有在综合治疗方案中联合使用，用于新诊断的APL患者的缓解诱导或维持。在这项研究中，将61名新诊断的APL受试者随机分为三个治疗组，即ATRA，As（2）O（3）以及两种药物的组合。通过血液学分析确定CR，通过实时定量RT-PCR检测PML-RARα（早幼粒细胞白血病-视黄酸受体α）融合转录本的肿瘤负荷，并通过临床检查评估副作用。还用细胞和分子生物学方法研究了可能涉及的机制。尽管三组的CR率均很高（>或= 90％），但达到CR的时间差异显着，而组合组的CR时间最短。该组还发现血小板计数较早恢复。与ATRA或As（2）O（3）单一疗法相比，联合疗法中CR的PML-RARα转录物倍数变化所反映的疾病负担显着降低（P <0.01）。合并后这种差异仍然存在（P <0.05）。重要的是，联合组中的所有20例均保留CR，而在接受8-30个月（中位数：18个月）的随访后，接受单药治疗的37例中有7例复发（P <0.05）。 ATRA和As（2）O（3）对PML-RARα癌蛋白的凋亡和降解的协同作用可能为临床联合治疗的优越疗效提供合理的解释。总之，就CR的质量和无病生存状况而言，用于APL缓解/维持治疗的ATRA / As（2）O（3）组合比单独使用两种药物中的任何一种都具有更好的效果。

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