Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia
Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia
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DOI：
10.1200/jco.2003.01.149
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发表时间：
2003-06-15
影响因子：
45.3
通讯作者：
Dombret, H
中科院分区：
文献类型：
--
作者：
Raffoux, E;Rousselot, P;Dombret, H
目的：三氧化二砷（ATO）能够诱导复发性急性早幼粒细胞白血病（APL）患者的高血液学应答率。临床前观察表明，全反式维甲酸（ATRA）可以强烈增强对ATO的应答。1998年至2001年，我们对20例复发性APL患者进行了一项单用ATO与ATO + ATRA的随机研究，所有患者之前均接受过含ATRA的化疗。主要目的是证明与ATO组相比，ATO/ATRA组获得完全缓解（CR）所需的时间显著缩短。结果：一个ATO加或不加ATRA诱导周期后的CR率为80%。临床和药代动力学观察表明，ATO在体内的主要作用机制是诱导APL细胞分化。两个治疗组的血液学和分子学缓解、达到CR所需的时间和结局相当。在16例CR患者中，3例在一个诱导周期后达到分子缓解的患者均接受了治疗诱导的高白细胞血症化疗。三个额外的患者接受进一步的额外ATO与或不ATRA周期转换后，以分子negativity.Conclusion：ATRA似乎没有显着改善ATO的反应，从APL复发的患者其他潜在的组合，包括ATO加化疗，必须进行测试。
Purpose: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL) Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO.Patients and methods: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response.Results: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity.Conclusion: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL Other potential combinations, including ATO plus chemotherapy, have to be tested.