Norsworthy Kelly J, Altman Jessica K
aJohns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland bNorthwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, USA.
Curr Opin Hematol. 2016 Mar;23(2):127-36. doi: 10.1097/MOH.0000000000000215.
Despite major advances in the treatment of acute promyelocytic leukemia (APL), high-risk APL still poses unique challenges. The purpose of this review is to outline current evidence for evaluation and management of high-risk APL and discuss areas of ongoing and future investigation.
With the changing treatment paradigm in APL and increasing use of arsenic trioxide (ATO), reports have questioned the relevance of classic prognostic factors. Despite advancements in therapy, early death remains a primary reason for treatment failure. A randomized, phase III trial demonstrated that all-trans retinoic acid + ATO is at least noninferior and may be superior to all-trans retinoic acid + chemotherapy in low/intermediate-risk APL. One phase III and multiple phase II trials have suggested a benefit of adding ATO to therapy of high-risk patients. Attempts at minimizing chemotherapy in high-risk disease have proven feasible with the use of gemtuzumab ozogamicin, but it is unlikely that cytotoxic chemotherapy will be completely eliminated in this patient population.
Treatment of high-risk APL has evolved significantly over the past 10 years and current scoring systems, management, and treatment regimens have been reviewed. There are as yet unresolved questions, including how to minimize early deaths and optimal therapy in an ATO era.
尽管急性早幼粒细胞白血病（APL）的治疗取得了重大进展，但高危APL仍然带来独特的挑战。本综述的目的是概述高危APL评估和管理的当前证据，并讨论正在进行和未来研究的领域。
随着APL治疗模式的改变以及三氧化二砷（ATO）使用的增加，有报告对经典预后因素的相关性提出质疑。尽管治疗取得了进展，但早期死亡仍然是治疗失败的主要原因。一项随机III期试验表明，在低/中危APL中，全反式维甲酸+ATO至少不差于且可能优于全反式维甲酸+化疗。一项III期试验和多项II期试验表明，在高危患者的治疗中添加ATO有益。使用吉妥珠单抗奥唑米星已证明在高危疾病中尽量减少化疗是可行的，但在该患者群体中不太可能完全消除细胞毒性化疗。
在过去10年中，高危APL的治疗有了显著进展，目前的评分系统、管理和治疗方案已得到综述。仍有未解决的问题，包括如何在ATO时代尽量减少早期死亡以及最佳治疗方案。
