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使用博纳吐单抗清除儿童B细胞急性淋巴细胞白血病微小残留病阳性:来自微滴式数字PCR和流式细胞术的见解

Clearing MRD positivity with blinatumomab in pediatric B-cell acute lymphoblastic leukemia: insights from droplet digital PCR and flow cytometry.

作者信息

Tang Xue, Liu Siyu, Hu Yanni, Chen Fen, Wang Lulu, Li Tonghui, Liu Yi, Zhou Guichi, Liu Shilin, Liu Sixi, Wen Feiqiu, Wang Ying, Mai Huirong, Xiao Jianwen

机构信息

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.

Department of Hematology and Oncology, Shenzhen Children's Hospital of China Medical University, Shenzhen, China.

出版信息

Ann Hematol. 2025 Jan;104(1):559-564. doi: 10.1007/s00277-024-06126-8. Epub 2024 Dec 13.

DOI:10.1007/s00277-024-06126-8
PMID:39668199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11868138/
Abstract

Blinatumomab has shown to improve survival outcomes in B-cell acute lymphoblastic leukemia (B-ALL) patients with measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC). However, data on blinatumomab clearing MRD with high sensitivity remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating low levels of MRD, as detected by droplet digital PCR (ddPCR) but undetectable by MFC, in children with B-ALL. Patients (n = 9) whose MRD was undetectable by MFC but detectable by ddPCR after chemotherapy and followed by blinatumomab consolidation were included retrospectively. After the administration of blinatumomab, 5 out of 9 patients (55.56%) successfully achieved undetectable levels of ddPCR-MRD. Notably, among the 4 patients with BCR::ABL1 gene-positive acute lymphoblastic leukemia (ALL), only one achieved gene negativity. Starting from the initiation of blinatumomab treatment, with a median follow-up of 12 months, all patients remained in complete remission. Our study was the first to demonstrate that blinatumomab could further eradicate ddPCR MRD after patients achieve MFC-MRD undetectable status in B-ALL patients.

摘要

博纳吐单抗已被证明可改善通过多参数流式细胞术(MFC)检测到有可测量残留病(MRD)的B细胞急性淋巴细胞白血病(B-ALL)患者的生存结局。然而,关于博纳吐单抗以高灵敏度清除MRD的数据仍然很少。本研究评估了博纳吐单抗在根除B-ALL儿童中低水平MRD的有效性,这些低水平MRD通过液滴数字PCR(ddPCR)检测到,但MFC检测不到。回顾性纳入了9例患者,这些患者在化疗后MFC检测不到MRD,但ddPCR可检测到,随后接受博纳吐单抗巩固治疗。给予博纳吐单抗后,9例患者中有5例(55.56%)成功实现ddPCR-MRD检测不到水平。值得注意的是,在4例BCR::ABL1基因阳性急性淋巴细胞白血病(ALL)患者中,只有1例实现了基因阴性。从开始使用博纳吐单抗治疗起,中位随访12个月,所有患者均保持完全缓解。我们的研究首次证明,在B-ALL患者达到MFC-MRD检测不到状态后,博纳吐单抗可进一步根除ddPCR MRD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3c4/11868138/95ff160964b8/277_2024_6126_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3c4/11868138/95ff160964b8/277_2024_6126_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3c4/11868138/95ff160964b8/277_2024_6126_Fig1_HTML.jpg

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Haematologica. 2024 Dec 1;109(12):4089-4094. doi: 10.3324/haematol.2024.285119.
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3
Ultrasensitive NGS MRD assessment in Ph+ ALL: Prognostic impact and correlation with RT-PCR for BCR::ABL1.Ph+ 阳性急性淋巴细胞白血病中超敏 NGS MRD 评估:与 BCR::ABL1 的 RT-PCR 检测的相关性及其预后意义。
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PAX5 epigenetically orchestrates CD58 transcription and modulates blinatumomab response in acute lymphoblastic leukemia.PAX5 通过表观遗传调控 CD58 的转录,调节急性淋巴细胞白血病中blinatumomab 的反应。
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