Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China.
Cytometry B Clin Cytom. 2024 May;106(3):181-191. doi: 10.1002/cyto.b.22170. Epub 2024 Mar 27.
Measurable residual disease (MRD) is an important prognostic indicator of chronic lymphocytic leukemia (CLL). Different flow cytometric panels have been developed for the MRD assessment of CLL in Western countries; however, the application of these panels in China remains largely unexplored.
Owing to the requirements for high accuracy, reproducibility, and comparability of MRD assessment in China, we investigated the performance of a flow cytometric approach (CD45-ROR1 panel) to assess MRD in patients with CLL. The European Research Initiative on CLL (ERIC) eight-color panel was used as the "gold standard."
The sensitivity, specificity, and concordance rate of the CD45-ROR1 panel in the MRD assessment of CLL were 100% (87/87), 88.5% (23/26), and 97.3% (110/113), respectively. Two of the three inconsistent samples were further verified using next-generation sequencing. In addition, the MRD results obtained from the CD45-ROR1 panel were positively associated with the ERIC eight-color panel results for MRD assessment (R = 0.98, p < 0.0001). MRD detection at low levels (≤1.0%) demonstrated a smaller difference between the two methods (bias, -0.11; 95% CI, -0.90 to 0.68) than that at high levels (>1%). In the reproducibility assessment, the bias was smaller at three data points (within 24, 48, and 72 h) in the CD45-ROR1 panel than in the ERIC eight-color panel. Moreover, MRD levels detected using the CD45-ROR1 panel for the same samples from different laboratories showed a strong statistical correlation (R = 0.99, p < 0.0001) with trivial interlaboratory variation (bias, 0.135; 95% CI, -0.439 to 0.709). In addition, the positivity rate of MRD in the bone marrow samples was higher than that in the peripheral blood samples.
Collectively, this study demonstrated that the CD45-ROR1 panel is a reliable method for MRD assessment of CLL with high sensitivity, reproducibility, and reliability.
微小残留病（MRD）是慢性淋巴细胞白血病（CLL）的一个重要预后指标。西方国家已经开发出不同的流式细胞术检测面板用于 CLL 的 MRD 评估；然而，这些面板在中国的应用仍在很大程度上未被探索。
由于在中国对 MRD 评估的准确性、可重复性和可比性的要求很高，我们研究了流式细胞术方法（CD45-ROR1 面板）在 CLL 患者 MRD 评估中的性能。采用欧洲慢性淋巴细胞白血病研究倡议（ERIC）八色面板作为“金标准”。
CD45-ROR1 面板在 CLL 的 MRD 评估中的灵敏度、特异性和一致性率分别为 100%（87/87）、88.5%（23/26）和 97.3%（110/113）。三个不一致样本中的两个进一步使用下一代测序进行了验证。此外，CD45-ROR1 面板获得的 MRD 结果与 ERIC 八色面板的 MRD 评估结果呈正相关（R=0.98，p<0.0001）。低水平（≤1.0%）MRD 检测结果表明两种方法之间的差异较小（偏差，-0.11；95%CI，-0.90 至 0.68），而高水平（>1%）MRD 检测结果之间的差异较大。在重复性评估中，CD45-ROR1 面板的三个数据点（24、48 和 72 小时内）的偏差小于 ERIC 八色面板。此外，来自不同实验室的相同样本使用 CD45-ROR1 面板检测到的 MRD 水平具有很强的统计学相关性（R=0.99，p<0.0001），实验室间差异较小（偏差，0.135；95%CI，-0.439 至 0.709）。此外，骨髓样本的 MRD 阳性率高于外周血样本。
总的来说，这项研究表明 CD45-ROR1 面板是一种可靠的 CLL MRD 评估方法，具有高灵敏度、可重复性和可靠性。
