Role of Arsenic Trioxide in Acute Promyelocytic Leukemia
Role of Arsenic Trioxide in Acute Promyelocytic Leukemia
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DOI：
10.1007/s11864-012-0223-3
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发表时间：
2013-06-01
影响因子：
4.3
通讯作者：
Seymour, John F.
中科院分区：
文献类型：
--
作者：
Iland, Harry J.;Seymour, John F.
急性早幼粒细胞白血病（APL）是急性髓细胞白血病的一种独特亚型，其特征在于不同的临床、形态学、细胞遗传学和分子异常。它与由于弥散性血管内凝血和纤维蛋白溶解亢进引起的早期出血性死亡的显著风险相关。APL的预后已显着改善后，全反式维甲酸（ATRA）的介绍，并结合蒽环类药物为基础的化疗在诱导和巩固。诊断时白色细胞计数> 10 x 10（9）/L的高危APL患者，在巩固治疗期间加入中等或高剂量阿糖胞苷似乎也有益处。三氧化二砷（ATO）已被证明是更有效的比ATRA作为一个单一的代理，现在是常规用于治疗20%-30%的患者谁表现出疾病复发后，初步治疗ATRA和化疗。ATO的毒性特征与ATRA和细胞毒性化疗的毒性特征有很大不同，因此在治疗期间存在其自身的特定挑战。优化将ATO纳入初始治疗的策略是目前几个合作组试验的重点，重点是最大限度地减少甚至消除化疗的使用。对于标准风险APL患者，在诱导和巩固期间，ATRA加ATO无化疗似乎是足够的，但对于高风险APL患者，在诱导期间需要三联疗法，包括有限的蒽环类抗生素或吉妥珠单抗（GO）。关于化疗的最小量和所需的巩固周期数、ATO的最佳时间表和口服ATO给药的潜在效用，仍然存在不确定性。尽管目前APL治疗方案中通常包括长期口服维持治疗，但其价值仍存在争议，基于ATO的治疗的上级抗白血病疗效可能有助于其在未来的消除。
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia that is characterized by distinct clinical, morphological, cytogenetic, and molecular abnormalities. It is associated with a striking risk of early hemorrhagic death due to disseminated intravascular coagulation and hyperfibrinolysis. The prognosis of APL has improved dramatically following the introduction of all-trans retinoic acid (ATRA) and its combination with anthracycline-based chemotherapy during induction and consolidation. Patients with high-risk APL, defined by a white cell count > 10 x 10(9)/L at diagnosis, also appear to benefit from the addition of intermediate- or high-dose cytarabine during consolidation. Arsenic trioxide (ATO) has proved to be even more effective than ATRA as a single agent, and is now routinely used for the treatment of the 20%-30% of patients who manifest disease relapse after initial treatment with ATRA and chemotherapy. ATO has a toxicity profile that differs considerably from that of both ATRA and cytotoxic chemotherapy, and accordingly presents its own specific challenges during treatment. Optimizing a strategy for the incorporation of ATO into initial therapy is currently the focus of several cooperative group trials, with an emphasis on minimizing or even eradicating the use of chemotherapy. ATRA plus ATO without chemotherapy appears to be adequate during induction and consolidation for patients with standard-risk APL, but triple therapy that includes limited anthracycline or gemtuzumab ozogamicin (GO) during induction is required for high-risk APL. Uncertainty still exists regarding the minimum amount of chemotherapy and number of consolidation cycles necessary, the optimal scheduling of ATO, and the potential utility of oral ATO administration. Although prolonged oral maintenance therapy is usually included in most current APL treatment protocols, its value remains controversial, and the superior anti-leukemic efficacy of ATO-based therapy may facilitate its elimination in the future.