MRD in AML: does it already guide therapy decision-making?
MRD in AML: does it already guide therapy decision-making?
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DOI：
10.1182/asheducation-2016.1.356
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发表时间：
2016-12-01
影响因子：
3
通讯作者：
Schuurhuis, Gerrit Jan
中科院分区：
文献类型：
--
作者：
Ossenkoppele, Gert;Schuurhuis, Gerrit Jan
诊断时确定的预后因素可预测预后，而形态完全缓解（CR）的实现仍然是治疗期间的重要终点。治疗后残留病可能反映所有诊断和诊断后耐药机制/因素的总和；假设它的测量对指导治疗非常有用。将残留疾病（最小残留疾病[MRD]）定义为远低于5%胚细胞水平的可能性正在改变风险分类的格局。在这份手稿中，各种方法，所有不同的敏感性，特异性和发展阶段，以评估MRD进行了讨论。目前，最常用的两种方法是基于流式细胞术的免疫MRD （multiparameter flow cytometry [MPFC]）和实时定量聚合酶链反应评估的分子MRD。两者都有优点和缺点，并进行了详细的总结。许多针对儿童和成人的研究已经证明，通过MPFC或分子MRD检测急性髓性白血病（AML）在诱导和巩固后提供了强有力的预后信息。本文就这些研究进行综述。本综述的总体结论是，目前正在出现一种比形态学CR更好的疾病负担定义。流式或分子技术评估的MRD应成为AML临床试验的标准。抗体小组的统一、单细胞管系统的引入（用于确定残留的白血病干细胞）和标准化的分析程序将为个体风险评估铺平道路，并成为新药研究中生存的替代终点，有望加快AML药物的批准。
Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [ MRD]) far below the level of 5% blast cells is changing the landscape of risk classification. In this manuscript, the various methods, all different in sensitivity, specificity, and phase of development, to assess MRD are discussed. Currently, the 2 methods mostly used are flow cytometry-based immune MRD (multiparameter flow cytometry [MPFC]) and molecular MRD assessed by real-time quantitative polymerase chain reaction. Both have advantages and disadvantages that are summarized in detail. Many studies in children as well as adults already demonstrated that MRD detection by MPFC or molecular MRD provides strong prognostic information in acute myeloid leukemia (AML) after both induction and consolidation. These studies are summarized in this review. The general conclusion of this review is that a better definition of disease burden than morphological CR is now emerging. MRD assessed by flow or molecular techniques should become standard in every clinical trial in AML. Harmonization of antibody panels, introduction of single-cell tube systems (for determination of residual leukemic stem cells), and standardized analytical programs will pave the way for individual risk assessment and become a surrogate end point for survival in studies investigating new drugs, hopefully resulting in faster drug approval in AML.