Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, Chemnitzstrasse 33, Kiel, Germany.
Blood. 2012 Nov 29;120(23):4470-81. doi: 10.1182/blood-2012-06-379040. Epub 2012 Oct 2.
Significant improvements have been made in the treatment of acute lymphoblastic leukemia (ALL) during the past 2 decades, and measurement of submicroscopic (minimal) levels of residual disease (MRD) is increasingly used to monitor treatment efficacy. For a better comparability of MRD data, there are ongoing efforts to standardize MRD quantification using real-time quantitative PCR of clonal immunoglobulin and T-cell receptor gene rearrangements, real-time quantitative-based detection of fusion gene transcripts or breakpoints, and multiparameter flow cytometric immunophenotyping. Several studies have demonstrated that MRD assessment in childhood and adult ALL significantly correlates with clinical outcome. MRD detection is particularly useful for evaluation of treatment response, but also for early assessment of an impending relapse. Therefore, MRD has gained a prominent position in many ALL treatment studies as a tool for tailoring therapy with growing evidence that MRD supersedes most conventional stratification criteria at least for Ph-negative ALL. Most study protocols on adult ALL follow a 2-step approach with a first classic pretherapeutic and a second MRD-based risk stratification. Here we discuss whether and how MRD is ready to be used as main decisive marker and whether pretherapeutic factors and MRD are really competing or complementary tools to individualize treatment.
在过去的 20 年中，急性淋巴细胞白血病（ALL）的治疗取得了重大进展，并且越来越多地使用亚微观（微小）残留疾病（MRD）的测量来监测治疗效果。为了更好地比较 MRD 数据，正在努力使用克隆免疫球蛋白和 T 细胞受体基因重排的实时定量 PCR、基于实时定量的融合基因转录本或断点检测以及多参数流式细胞术免疫表型来标准化 MRD 定量。多项研究表明，儿童和成人 ALL 中的 MRD 评估与临床结果显著相关。MRD 检测特别有助于评估治疗反应，但也可用于早期评估即将发生的复发。因此，MRD 在许多 ALL 治疗研究中占据重要地位，作为一种调整治疗的工具，越来越多的证据表明 MRD 至少在 Ph-阴性 ALL 中取代了大多数常规分层标准。大多数成人 ALL 的研究方案采用两步法，首先是经典的治疗前，其次是基于 MRD 的风险分层。在这里，我们讨论了 MRD 是否以及如何准备好作为主要决定性标志物，以及治疗前因素和 MRD 是否真的是竞争还是互补的工具，用于个体化治疗。
