Highly sensitive single tube B-lymphoblastic leukemia/lymphoma minimal/measurable residual disease test robust to surface antigen directed therapy

IF 2.3 3区医学 Q3 MEDICAL LABORATORY TECHNOLOGY

Cytometry Part B: Clinical Cytometry Pub Date : 2023-03-30 DOI:10.1002/cyto.b.22120

Qi Gao, Ying Liu, Umut Aypar, Jeeyeon Baik, Dory Londono, Xiaotian Sun, Jingping Zhang, Yanming Zhang, Mikhail Roshal

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引用次数: 4

Abstract

Background

Measurement of minimal/measurable residual disease (MRD) in B-lymphoblastic leukemia/lymphoma (B-ALL) has become a routine clinical evaluation tool and remains the strongest predictor of treatment outcome. In recent years, new targeted anti-CD19 and anti-CD22 antibody-based and cellular therapies have revolutionized the treatment of the high-risk B-ALL. The new treatments raise challenges for diagnostic flow cytometry, which relies on the presence of specific surface antigens to identify the population of interest. So far, reported flow cytometry-based assays are developed to either achieve a deeper MRD level or to accommodate the loss of surface antigens post-target therapies, but not both.

Methods

We developed a single tube flow cytometry assay (14-color-16-parameters). The method was validated using 94 clinical samples as well as spike-in and replicate experiments.

Results

The assay was well suited for monitoring response to targeted therapies and reached a sensitivity below 10⁻⁵ with acceptable precision (coefficient of variation < 20%), accuracy, and interobserver variability (κ = 1).

Conclusions

The assay allows for sensitive disease detection of B-ALL MRD independent of CD19 and CD22 expression and allows uniform analysis of samples regardless of anti-CD19 and CD22 therapy.

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高度敏感的单管B淋巴细胞白血病/淋巴瘤最小/可测量的残留疾病测试，对表面抗原导向治疗具有稳健性。

背景：测量B淋巴细胞白血病/淋巴瘤（B-ALL）的最小/可测量残留疾病（MRD）已成为常规临床评估工具，并且仍然是治疗结果的最强预测因素。近年来，新的靶向抗CD19和抗CD22抗体和细胞疗法彻底改变了高危B-ALL的治疗。新的治疗方法对诊断性流式细胞术提出了挑战，流式细胞仪依赖于特定表面抗原的存在来识别感兴趣的人群。到目前为止，已报道的基于流式细胞术的检测方法是为了达到更深的MRD水平或适应靶向治疗后表面抗原的损失，但不是两者兼而有之。方法：我们开发了一种单管流式细胞仪测定法（14个颜色16个参数）。该方法使用94个临床样本以及刺入和重复实验进行了验证。结果：该测定法非常适合监测对靶向治疗的反应，并达到10-5以下的灵敏度和可接受的精度（变异系数）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytometry Part B: Clinical Cytometry 医学-病理学

CiteScore

6.80

自引率

32.40%

发文量

审稿时长

>12 weeks

期刊介绍： Cytometry Part B: Clinical Cytometry features original research reports, in-depth reviews and special issues that directly relate to and palpably impact clinical flow, mass and image-based cytometry. These may include clinical and translational investigations important in the diagnostic, prognostic and therapeutic management of patients. Thus, we welcome research papers from various disciplines related [but not limited to] hematopathologists, hematologists, immunologists and cell biologists with clinically relevant and innovative studies investigating individual-cell analytics and/or separations. In addition to the types of papers indicated above, we also welcome Letters to the Editor, describing case reports or important medical or technical topics relevant to our readership without the length and depth of a full original report.