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移植前流式细胞术、WT1表达和二代测序相结合用于微小残留病监测,在预测接受异基因移植的急性髓系白血病患者的预后方面很有效。

Combination of pre-transplant flow cytometry, WT1 expression, and NGS for MRD monitoring is potent in predicting the prognosis of AML receiving allogeneic transplantation.

作者信息

Liu Jie, Guo Dan, Lian Hanxi, Ding Peiwen, Liu Xin, Zhao Yanqiu, Li Huibo, Fan Shengjin

机构信息

Division of Hematology, Department of Medicine, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nan Gang District, Harbin, 150001, Heilongjiang Province, China.

NHC Key Laboratory of Cell Transplantation, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China.

出版信息

Ann Hematol. 2025 Apr 28. doi: 10.1007/s00277-025-06384-0.

DOI:10.1007/s00277-025-06384-0
PMID:40293465
Abstract

Minimal residual disease (MRD) monitoring has been demonstrated to important in predicting prognosis in acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the ideal time point and method remain unclear. Our study compared the prognostic value of multiparameter flow cytometry (MFC)-based and WT1 expression-based MRD a month before allo-HSCT [HSCT(-1 m)] and after allo-HSCT [HSCT(+ 1 m)], as well as next generation sequencing (NGS)-based MRD at HSCT(-1 m), HSCT(+ 1 m), 3 and 6 months after allo-HSCT [HSCT(+ 3 m) and HSCT(+ 6 m)] among 47 AML patients undergoing allo-HSCT. The MRD status by all the methods at HSCT(-1 m) was proved as a superior indicator with prognostic significance for disease progression, compared to that at HSCT(+ 1 m). For the NGS-based MRD, HSCT(+ 6 m) seemed to be the optimal detection time point, as supported by the optimal prognostic discrimination capability and the relatively high sensitivity for disease progression prediction. Moreover, our data showed that each individual method had some limitations in predicting prognosis; however, pre-transplant MRD monitoring by the combination of MFC, WT1 and NGS could greatly increase the sensitivity (100%) of identifying disease progression and greatly improve prognostic stratification. Our study may provide insights into the optimal time point and methodology for MRD monitoring in AML following allo-HSCT.

摘要

微小残留病(MRD)监测已被证明在预测接受异基因造血干细胞移植(allo-HSCT)的急性髓系白血病(AML)患者的预后方面具有重要意义,但理想的时间点和方法仍不明确。我们的研究比较了基于多参数流式细胞术(MFC)和基于WT1表达的MRD在allo-HSCT前1个月[HSCT(-1 m)]和allo-HSCT后1个月[HSCT(+1 m)]的预后价值,以及基于二代测序(NGS)的MRD在HSCT(-1 m)、HSCT(+1 m)、allo-HSCT后3个月和6个月[HSCT(+3 m)和HSCT(+6 m)]时的预后价值,研究对象为47例接受allo-HSCT的AML患者。与HSCT(+1 m)时相比,HSCT(-1 m)时所有方法检测的MRD状态被证明是疾病进展的具有预后意义的更好指标。对于基于NGS的MRD,HSCT(+6 m)似乎是最佳检测时间点,这得到了最佳预后判别能力和对疾病进展预测相对较高敏感性的支持。此外,我们的数据表明,每种单独的方法在预测预后方面都有一些局限性;然而,通过MFC、WT1和NGS联合进行移植前MRD监测可以大大提高识别疾病进展的敏感性(100%),并大大改善预后分层。我们的研究可能为allo-HSCT后AML患者MRD监测的最佳时间点和方法提供见解。

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本文引用的文献

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Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia.通过WT1基因表达和流式细胞术整合可测量残留病,可识别急性髓系白血病中具有高复发风险的儿科患者。
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流式细胞术检测 MDS/AML 或 AML 成人患者异基因造血细胞移植前微小残留病的相对预后价值。
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