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流式细胞术检测可测量残留病:385例急性髓系白血病连续病例的检测验证与特征分析

Measurable Residual Disease Analysis by Flow Cytometry: Assay Validation and Characterization of 385 Consecutive Cases of Acute Myeloid Leukemia.

作者信息

Jum'ah Husam A, Otteson Gregory E, Timm Michael M, Weybright Matthew J, Shi Min, Horna Pedro, Jevremovic Dragan, Reichard Kaaren K, Olteanu Horatiu

机构信息

Division of Hematopathology, Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Cancers (Basel). 2025 Mar 29;17(7):1155. doi: 10.3390/cancers17071155.

Abstract

: Acute myeloid leukemia (AML) is a biologically heterogeneous malignancy with a variable prognosis. Despite many patients achieving complete remission, relapse remains common, underscoring the need for effective prognostic markers. Measurable residual disease (MRD) has emerged as a critical prognostic indicator, associated with higher relapse risk and shorter survival. This study reports on our initial experience of MRD detection by flow cytometry in 385 bone marrow samples from 126 AML patients. : The flow cytometry MRD assay, validated according to stringent consensus recommendations, consists of a 3-tube, 10-color panel incorporating a broad spectrum of lineage differentiation markers. Analytical specificity, sensitivity, precision, and reproducibility were evaluated, demonstrating the assay's robustness. : The results reveal distinct immunophenotypic aberrancies in all AML cases, with consistent identification of aberrant immunophenotypes in follow-up specimens. AML MRD was detected in 32 out of 126 patients (25%) and in 77 out of 385 analyses (20%), with a median aberrant blast percentage of 1.87% (range, 0.01-12). A change in immunophenotype was documented in 21% of the MRD-positive cases. MRD positivity detected in the first sample studied was associated with reduced overall survival (HR: 5.153; < 0.0001). : Our findings support the integration of flow cytometric MRD analysis into routine clinical practice to enhance risk stratification and treatment planning for AML patients, as currently recommended by professional guidelines.

摘要

急性髓系白血病(AML)是一种生物学上异质性的恶性肿瘤,预后各不相同。尽管许多患者实现了完全缓解,但复发仍然很常见,这突出了对有效预后标志物的需求。可测量残留病(MRD)已成为一个关键的预后指标,与更高的复发风险和更短的生存期相关。本研究报告了我们通过流式细胞术检测126例AML患者385份骨髓样本中MRD的初步经验。

流式细胞术MRD检测方法根据严格的共识建议进行了验证,由一个包含广泛谱系分化标志物的3管10色检测板组成。对分析特异性、敏感性、精密度和可重复性进行了评估,证明了该检测方法的稳健性。

结果显示,所有AML病例均存在明显的免疫表型异常,在后续样本中能一致识别出异常免疫表型。126例患者中有32例(25%)检测到AML MRD,385次分析中有77次(20%)检测到,异常原始细胞百分比中位数为1.87%(范围为0.01 - 12)。21%的MRD阳性病例记录到免疫表型发生了变化。在首个研究样本中检测到的MRD阳性与总生存期缩短相关(HR:5.153;P < 0.0001)。

我们的研究结果支持将流式细胞术MRD分析纳入常规临床实践,以加强AML患者的风险分层和治疗规划,正如专业指南目前所推荐的那样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2804/11987847/a94ce850e663/cancers-17-01155-g001.jpg

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