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强化急性髓系白血病治疗——利用残留病检测监测反应以指导治疗决策

Enhancing acute myeloid leukemia therapy - monitoring response using residual disease testing as a guide to therapeutic decision-making.

作者信息

Tomlinson Benjamin, Lazarus Hillard M

机构信息

a Department of Medicine , University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center , Cleveland , OH , USA.

出版信息

Expert Rev Hematol. 2017 Jun;10(6):563-574. doi: 10.1080/17474086.2017.1326811. Epub 2017 May 12.

Abstract

Current standards for monitoring the response of acute myeloid leukemia (AML) are based on morphologic assessments of the bone marrow and recovery of peripheral blood counts. A growing experience is being developed to enhance the detection of small amounts of AML, or minimal residual disease (MRD). Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD. Expert commentary: While MRD monitoring is standard of care in some leukemia subsets such as acute promyelocytic leukemia, this approach for the broader AML population does not universally predict outcomes as some patients may experience relapse in the setting of undetectable leukemia while others show no obvious disease progression despite MRD positivity. However, there are instances where MRD can identify patients at increased risk for relapse that may change recommended therapy. Currently, prospective investigations to define clinically relevant MRD thresholds are ongoing. Risk-adapted trials are needed to best define the use of MRD in the follow up of AML patients after initial induction therapy.

摘要

目前监测急性髓系白血病(AML)缓解情况的标准基于骨髓形态学评估和外周血细胞计数的恢复。为提高对少量AML(即微小残留病,MRD)的检测,相关经验正在不断积累。涵盖领域:可用技术包括白血病相关免疫表型(LAIP)的多色流式细胞术(MFC)、用于检测融合基因和突变基因(RUNX1-RUNX1T1、CBFB-MYH11和NPM1)的定量逆转录聚合酶链反应(QRT-PCR)、WT1等基因的过表达检测以及用于MRD检测的下一代测序(NGS)。专家评论:虽然MRD监测在某些白血病亚组(如急性早幼粒细胞白血病)中是标准治疗手段,但对于更广泛的AML患者群体,这种方法并不能普遍预测预后,因为一些患者在白血病检测不到的情况下可能会复发,而另一些患者尽管MRD呈阳性但并未出现明显的疾病进展。然而,在某些情况下,MRD可以识别出复发风险增加的患者,这可能会改变推荐的治疗方案。目前,确定临床相关MRD阈值的前瞻性研究正在进行中。需要进行风险适应性试验,以最好地确定MRD在AML患者初始诱导治疗后的随访中的应用。

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