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急性髓系白血病中可测量残留病的临床应用。

Clinical Use of Measurable Residual Disease in Acute Myeloid Leukemia.

机构信息

Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Mølleparkvej 4, DK-9000, Aalborg, Denmark.

Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

出版信息

Curr Treat Options Oncol. 2019 Mar 14;20(4):28. doi: 10.1007/s11864-019-0627-4.

Abstract

Treatment of acute myeloid leukemia (AML) remains a high-risk venture for the patient suffering from the disease. There is a real risk of succumbing to the treatment rather than the disease, and even so, cure is much less than certain. Since the establishment of complete remission as a prerequisite for cure in the 1960s, a number of years passed before advanced techniques for detecting minute amounts of disease matured sufficiently for clinical implementation. The two main techniques for detection of measurable residual disease (MRD) remain qPCR and multicolor flow cytometry. When performed in expert laboratories, both these modalities offer treating physicians excellent opportunity to follow the amount of residual disease upon treatment and offer unparalleled prognostication. In some AML and age group subsets, evidence now exist to support the choice of both proceeding to allogeneic transplant and not doing so. In other AML subgroups, MRD has sufficient discriminative power to identify patients likely to benefit from allogeneic transplant and patients likely not to. After treatment or transplantation, follow-up by molecular techniques can, with high certainty, predict relapse months before bone marrow function deterioration. On the other hand, options upon so-called molecular relapse are less well tested but recent evidence supports the use of azacitidine both in transplanted patients and patients consolidated with chemotherapy. In conclusion, MRD testing during treatment is a superb prognosticator and a major tool when choosing whether a patient should be transplanted or not. The exact use of MRD testing after treatment is less well defined but evidence is mounting for the instigation of treatment upon rising MRD levels (pre-emptive treatment) before morphologically detectable relapse.

摘要

治疗急性髓系白血病 (AML) 对患者来说仍然是一项高风险的冒险。患者有因治疗而不是疾病而死亡的真正风险,即使如此,治愈的可能性也远不能确定。自 20 世纪 60 年代将完全缓解确立为治愈的前提以来,经过多年的发展,用于检测微量疾病的先进技术才成熟到足以进行临床应用。检测可测量残留疾病 (MRD) 的两种主要技术仍然是 qPCR 和多色流式细胞术。在专家实验室进行时,这两种方法都为治疗医生提供了极好的机会,可在治疗过程中跟踪残留疾病的数量,并提供无与伦比的预后。在某些 AML 和年龄组亚组中,现在有证据支持选择进行同种异体移植和不进行同种异体移植。在其他 AML 亚组中,MRD 具有足够的区分能力,可以识别可能受益于同种异体移植的患者和不太可能受益的患者。治疗或移植后,通过分子技术进行随访,可以在骨髓功能恶化前数月,非常确定地预测复发。另一方面,所谓分子复发后的选择方案的测试效果较差,但最近的证据支持在移植患者和接受化疗巩固的患者中使用阿扎胞苷。总之,治疗期间的 MRD 检测是一种出色的预后指标,也是选择是否进行移植的主要工具。治疗后 MRD 检测的确切用途定义不明确,但有越来越多的证据支持在形态学可检测到复发之前,根据 MRD 水平升高(抢先治疗)启动治疗。

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