Single Cycle of Arsenic Trioxide-Based Consolidation Chemotherapy Spares Anthracycline Exposure in the Primary Management of Acute Promyelocytic Leukemia
Single Cycle of Arsenic Trioxide-Based Consolidation Chemotherapy Spares Anthracycline Exposure in the Primary Management of Acute Promyelocytic Leukemia
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DOI：
10.1200/jco.2009.25.5158
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发表时间：
2010-02-20
影响因子：
45.3
通讯作者：
Gallagher, Robert E.
中科院分区：
文献类型：
--
作者：
Gore, Steven D.;Gojo, Ivana;Gallagher, Robert E.
目的基于全反式维甲酸 (ATRA) 的急性早幼粒细胞白血病 (APL) 治疗后 5 年无事件生存率平均为 70%。虽然三氧化二砷 (ATO) 可以诱导 95% 的复发患者缓解，但很少有研究探讨将 ATO 纳入 APL 的初级治疗。本研究检验了旨在减少与其他细胞毒性药物接触的治疗方案中基于 ATO 的单周期巩固治疗的疗效。患者和方法在使用 ATRA 和柔红霉素 (DRN) 诱导后，未经治疗的 APL 患者接受了 3 天的阿糖胞苷和 DRN，随后从第 8 天开始接受 30 剂 ATO。分子缓释者接受了 2 年的基于风险的维持治疗。结果 45 名接受治疗的患者中，有 41 名患者接受了基于风险的维持治疗。诱导治疗达到缓解；四名患者死亡（一名在治疗开始前死亡）。 37 名患者接受了巩固和维持治疗；其中一名患者复发（中枢神经系统），一名患者在维持治疗期间缓解后死亡（肝镰状细胞危象）。中位随访时间为 2.7 年，预计无病生存率为 90%；所有患者的总生存率为 88%。尽管蒽环类药物总剂量仅为 360 mg/m(2)，但 20% 的患者心脏射血分数下降了≥20%。结论这些数据与最近使用 ATO 进行 APL 初级治疗的其他研究相结合，证明了 ATO 在这种可治愈疾病的初级治疗中可以发挥的重要作用。未来的研究应继续关注降低治疗的毒性而不增加复发率。
PurposeEvent-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents.Patients and MethodsAfter induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy.ResultsForty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m(2), cardiac ejection fraction decreased by >= 20% in 20% of patients.ConclusionThese data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.