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一种新型流式细胞术检测方案,用于检测抗 CD19 治疗后 B 淋巴细胞白血病/淋巴瘤患者的残留病。

A novel flow cytometric assay for detection of residual disease in patients with B-lymphoblastic leukemia/lymphoma post anti-CD19 therapy.

机构信息

Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.

出版信息

Cytometry B Clin Cytom. 2018 Jan;94(1):112-120. doi: 10.1002/cyto.b.21482. Epub 2016 Sep 23.

Abstract

BACKGROUND

Residual disease detection following therapy is an important prognostic variable in B-lymphoblastic leukemia (B-LL). Most flow cytometric strategies for detecting B cell malignancy utilize CD19 to identify B cells. With growing use of anti-CD19 targeted therapies, alternative strategies are needed for residual disease detection. We describe an approach for residual disease detection in this setting.

METHODS

A novel combination was designed using expression of CD22 or CD24 (without CD66b) for B cell detection in combination with markers aberrantly expressed in B-LL (CD10, CD20, CD34, CD38, and CD45). The performance characteristics of this combination were evaluated and compared to a standard, validated B-LL MRD assay using 10 known negative samples, 10 overtly positive samples, and 11 post-therapy samples (prior therapy other than anti-CD19 therapy). Subsequently, results from the first 100 samples on which the new tube was performed were reviewed.

RESULTS

The described combination performed well in the initial analysis of 31 samples with all negative and positive samples correctly classified. In positive samples, the percentage of abnormal cells correlated well between the standard and new assay. Evaluation of the first 100 samples demonstrated good performance with adequate detection of CD19-positive and CD19-negative B-LL. Additionally, it was observed that patients receiving anti-CD19 therapies demonstrate an increased proportion of CD19-negative progenitors.

CONCLUSIONS

These preliminary findings describe a strategy that performs well for residual disease detection in B-LL post anti-CD19 therapy. Such alternative strategies will become more important as the use of targeted immunotherapies becomes more common. © 2016 International Clinical Cytometry Society.

摘要

背景

治疗后残留疾病的检测是 B 淋巴细胞白血病(B-LL)的一个重要预后变量。大多数用于检测 B 细胞恶性肿瘤的流式细胞术策略都利用 CD19 来鉴定 B 细胞。随着抗 CD19 靶向治疗的广泛应用,需要寻找替代策略来检测残留疾病。我们描述了在这种情况下检测残留疾病的一种方法。

方法

设计了一种新的组合,使用 CD22 或 CD24(无 CD66b)表达来检测 B 细胞,与在 B-LL 中异常表达的标志物(CD10、CD20、CD34、CD38 和 CD45)结合使用。评估了该组合的性能特征,并与使用 10 个已知阴性样本、10 个明显阳性样本和 11 个治疗后样本(除抗 CD19 治疗以外的其他治疗)的标准、经过验证的 B-LL MRD 测定进行比较。随后,回顾了新管进行的前 100 个样本的结果。

结果

在对 31 个样本的初始分析中,该组合表现良好,所有阴性和阳性样本均正确分类。在阳性样本中,标准和新检测之间的异常细胞百分比相关性良好。对前 100 个样本的评估表明,该方法性能良好,能够充分检测 CD19 阳性和 CD19 阴性 B-LL。此外,还观察到接受抗 CD19 治疗的患者中 CD19 阴性祖细胞的比例增加。

结论

这些初步结果描述了一种在接受抗 CD19 治疗后用于 B-LL 残留疾病检测的策略,该策略性能良好。随着靶向免疫疗法的应用越来越广泛,这种替代策略将变得更加重要。©2016 年国际临床细胞学会。

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