Laboratory Medicine Program, Hematopathology, University Health Network, Toronto, ON M5G 2C4, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Curr Oncol. 2021 Mar 30;28(2):1376-1387. doi: 10.3390/curroncol28020131.
Measurable (minimal) residual disease (MRD) is an established, key prognostic factor in adult B-cell acute lymphoblastic leukemia (B-ALL), and testing for MRD is known to be an important tool to help guide treatment decisions. The clinical value of MRD testing depends on the accuracy and reliability of results. Currently, there are no Canadian provincial or national guidelines for MRD testing in adult B-ALL, and consistent with the absence of such guidelines, there is no uniform Ontario MRD testing consensus. Moreover, there is great variability in Ontario in MRD testing with respect to where, when, and by which technique, MRD testing is performed, as well as in how the results are interpreted. To address these deficiencies, an expert multidisciplinary working group was convened to define consensus recommendations for improving the provision of such testing. The expert panel recommends that MRD testing should be implemented in a centralized manner to ensure expertise and accuracy in testing for this low volume indication, thereby to provide accurate, reliable results to clinicians and patients. All adult patients with B-ALL should receive MRD testing after induction chemotherapy. Philadelphia chromosome (Ph)-positive patients should have ongoing monitoring of MRD during treatment and thereafter, while samples from Ph-negative B-ALL patients should be tested at least once later during treatment, ideally at 12 to 16 weeks after treatment initiation. In Ph-negative adult B-ALL patients, standardized, ideally centralized, protocols must be used for MRD testing, including both flow cytometry and immunoglobulin () heavy chain and T-cell receptor () gene rearrangement analysis. For Ph-positive B-ALL patients, MRD testing using a standardized protocol for reverse transcription real-time quantitative PCR (RT-qPCR) for the gene fusion transcript is recommended, with gene rearrangement analysis done in parallel likely providing additional clinical information.
可测量（最小）残留病（MRD）是成人 B 细胞急性淋巴细胞白血病（B-ALL）的既定关键预后因素，检测 MRD 已知是帮助指导治疗决策的重要工具。MRD 检测的临床价值取决于结果的准确性和可靠性。目前，加拿大省级或全国范围内均没有成人 B-ALL 患者的 MRD 检测指南，而且与缺乏此类指南一致的是，安大略省也没有统一的 MRD 检测共识。此外，安大略省在 MRD 检测方面存在很大的差异，包括检测地点、时间、采用的技术以及对结果的解释方式。为了解决这些不足，召集了一个专家多学科工作组来制定改善此类检测的共识建议。专家组建议应集中进行 MRD 检测，以确保在这种低容量指征的检测中具有专业知识和准确性，从而为临床医生和患者提供准确、可靠的结果。所有成人 B-ALL 患者在诱导化疗后都应接受 MRD 检测。费城染色体（Ph）阳性患者在治疗期间和之后应持续监测 MRD，而 Ph 阴性 B-ALL 患者的样本应在治疗过程中至少再检测一次，理想情况下在治疗开始后 12 至 16 周。在 Ph 阴性成人 B-ALL 患者中，必须使用标准化的、理想的集中式方案进行 MRD 检测，包括流式细胞术和免疫球蛋白（Ig）重链和 T 细胞受体（TCR）基因重排分析。对于 Ph 阳性 B-ALL 患者，建议使用标准化方案进行逆转录实时定量聚合酶链反应（RT-qPCR）检测 基因融合转录本的 MRD 检测，同时并行进行基因重排分析可能会提供更多的临床信息。
