多突变基因数字PCR联合多参数流式细胞术监测可检测残留病预测急性髓系白血病患者复发风险

Monitoring measurable residual disease with multigene mutations ddPCR combined with multiparametric flow cytometry to predict relapse risk in patients with acute myeloid leukemia

    摘要
  • 摘要:
    目的 分析应用微滴式数字PCR（droplet digital PCR，ddPCR）联合多参数流式细胞术（multiparametric flow cytometry，MFC）监测可检测残留病（measurable residual disease，MRD）预测急性髓系白血病（acute myeloid leukemia，AML）患者的复发风险价值。
    方法 收集河北大学附属医院2018年1月至2025年1月收治的78例联合应用MFC及ddPCR方法监测MRD的新诊断AML患者的临床资料。回顾性分析其MRD阴性率、复发率、无复发生存（relapse-free survival，RFS）率、总生存（overall survival，OS）率。比较不同MRD检测方法单独使用及联合应用所判定的MRD阴性患者与阳性患者间生存差异。
    结果 中位随访时间为17.0（2.4～86.7）个月，中位监测突变基因数1（1～3）个，MFC-MRD阴性组2年RFS显著优于阳性组。ddPCR-MRD阴性组2年RFS显著优于阳性组。将MFC与ddPCR方法联合应用，MRD阴性组2年RFS优势进一步扩大。MFC-MRD阴性组同时展现了OS优势。
    结论 通过ddPCR方法监测多突变基因MRD在预测AML患者的复发风险中有一定价值，将MFC与ddPCR联合应用检测MRD，能够更精确地预测患者的复发风险及生存。

     

    Abstract:
    Objective  To evaluate the prognostic value of droplet digital PCR (ddPCR) in conjunction with multiparametric flow cytometry (MFC) for measurable residual disease (MRD) detection in predicting relapse risk in patients with acute myeloid leukemia (AML).
    Methods  In this retrospective cohort study, we have analyzed 78 newly diagnosed patients with AML who underwent combined MRD monitoring using MFC and ddPCR at The Affiliated Hospital of Hebei University (January 2018-January 2025). Clinical outcomes-including MRD negativity rates, cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS)-were systematically evaluated. Prognostic discrimination between the MRD-negative and MRD-positive subgroups was compared across standalone and combined detection approaches.
    Results With a median follow-up of 17 months (range: 2.4-86.7) and a median of one mutation tracked per patient (range: 1-3), both MFC-MRD and ddPCR-MRD negative subgroups demonstrated superior 2-year RFS compared with MRD-positive counterparts. Notably, combined MFC/ddPCR monitoring enhanced prognostic discrimination, with MRD-negative patients achieving significantly prolonged 2-year RFS compared with MRD-positive patients. MFC-MRD negativity independently predicted improved 2-year OS.
    Conclusion ddPCR-based multigene MRD profiling provides significant independent prognostic value in patients with AML. The synergistic application of MFC and ddPCR enables superior predictive accuracy for relapse risk and survival outcomes, supporting its integration into standardized MRD monitoring protocols.

     

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