Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710
Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710
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DOI：
10.1182/blood-2010-02-269621
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发表时间：
2010-11-11
期刊：
影响因子：
20.3
通讯作者：
Larson, Richard A.
中科院分区：
文献类型：
--
作者：
Powell, Bayard L.;Moser, Barry;Larson, Richard A.
三氧化二砷（As 2 O3）是治疗复发性急性早幼粒细胞白血病（APL）的一种高效治疗方法;其作为首次缓解患者的巩固治疗的作用尚未确定。我们将481例年龄>= 15岁的APL患者随机分为两组，一组接受维甲酸、阿糖胞苷和柔红霉素的标准诱导方案，随后接受维甲酸加柔红霉素的2个疗程的巩固治疗，另一组接受相同的诱导和巩固方案，诱导后立即接受2个疗程的As 2 O3巩固治疗。巩固治疗后，患者被随机分配到维甲酸单独或联合甲氨蝶呤和巯基嘌呤维持治疗一年。每组90%的患者达到缓解，并有资格接受分配的巩固治疗。三氧化二砷巩固治疗组患者的主要终点无事件生存率明显优于三氧化二砷巩固治疗组，3年时为80%，而三氧化二砷巩固治疗组为63%（分层对数秩检验，P <0.0001）。作为次要终点，As 2 O3组的生存率更高，3年时为86%，而As 2 O3组为81%（P = 0.059）。作为次要终点，As 2 O3组的无病生存率明显更好，3年时为90%，而As 2 O3组为70%（P < .0001）。在标准诱导和巩固治疗基础上加用As 2 O3巩固治疗可显著提高新诊断APL成人患者的无事件和无病生存率。本试验在clinicaltrials.gov（NCT 00003934）上注册。（血。2010;116（19）：3751-3757）
Arsenic trioxide (As2O3) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age >= 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As2O3 consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine. Ninety percent of patients on each arm achieved remission and were eligible to receive their assigned consolidation therapy. Event-free survival, the primary end point, was significantly better for patients assigned to receive As2O3 consolidation, 80% compared with 63% at 3 years (stratified log-rank test, P < .0001). Survival, a secondary end point, was better in the As2O3 arm, 86% compared with 81% at 3 years (P = .059). Disease-free survival, a secondary end point, was significantly better in the As2O3 arm, 90% compared with 70% at 3 years (P < .0001). The addition of As2O3 consolidation to standard induction and consolidation therapy significantly improves event-free and disease-free survival in adults with newly diagnosed APL. This trial was registered at clinicaltrials.gov (NCT00003934). (Blood. 2010;116(19):3751-3757)