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[多参数流式细胞术与实时定量聚合酶链反应检测费城染色体阳性急性B淋巴细胞白血病异基因造血干细胞移植前微小残留病的预后意义比较]

[Comparison of prognostic significance between multiparameter flow cytometry and real-time quantitative polymerase chain reaction in the detection of minimal residual disease of Philadelphia chromosome-positive acute B lymphocytic leukemia before allogeneic hematopoietic stem cell transplantation].

作者信息

Wang X Y, Chang Y J, Liu Y R, Qin Y Q, Xu L P, Wang Y, Zhang X H, Yan C H, Sun Y Q, Huang X J, Zhao X S

机构信息

Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2021 Feb 14;42(2):116-123. doi: 10.3760/cma.j.issn.0253-2727.2021.02.005.

Abstract

To explore the different values of minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RQ-PCR) before hematopoietic stem cell transplantation (HSCT) for predicting relapse, leukemia-free survival (LFS) , and overall survival (OS) in Philadelphia chromosome-positive ALL (Ph(+) ALL) . A retrospective study (=280) was performed. MRD was determined using multiparameter flow cytometry and RQ-PCR. MRD analysis with MFC and RQ-PCR of the BCR-ABL fusion transcript showed a strong correlation before transplantation. The positive rates of MRD detected by MFC and RQ-PCR before transplantation were 25.7% (72/280) and 60.7% (170/280) , respectively. MFC MRD-positive (MRDpos) Ph(+) ALL patients had a higher 3 year cumulative incidences of relapse (CIR) than did MFC MRD-negative (MRDneg) Ph(+) ALL patients (23.6% 8.6%; <0.001) . However, the RQ-PCR MRDpos group had similar rates of 3 year OS, LFS, and NRM compared with those in the RQ-PCR MRDneg group. Moreover, patients with RQ-PCR MRD ≥1% experienced higher 3 year CIR (23.1% 11.4%; =0.032) , lower LFS (53.8% 74.4%; =0.015) , and OS (57.7% 79.1%; =0.009) compared with the RQ-PCR MRD<1% group. Multivariate analyses confirmed the association of MFC MRD status and RQ-PCR MRD ≥1% with outcomes (<0.05) . The sensitivity, specificity, positive predictive value (PPV) , and negative predictive value (NPV) of MFC detection MRD to predict recurrence were 48.50%, 77.56%, 23.62%, and 87.16%, respectively. Moreover, the sensitivity, specificity, PPV, and NPV were 23.00%, 88.59%, 17.15%, and 91.84%, respectively, when RQ-PCR MRD ≥1% was used to predict recurrence. Additionally, the sensitivity, specificity, PPV, and NPV were 54.29%, 73.88%, 45.7% and 91.87%, respectively, when MRD-positive status before transplantation (MFC MRDpos or RQ-PCR MRD ≥1%) was used to predict recurrence after transplantation. Both MFC and RQ-PCR detection of pretransplant MRD levels can predict the prognosis of Ph(+) B-ALL patients receiving allogeneic HSCT. MFC MRD-positive status before transplantation is the risk factor of leukemia recurrence after transplantation. The combined use of the two methods (MFC MRDpos or RQ-PCR MRD ≥1%) can improve the sensitivity, PPV, and NPV of predicting recurrence and help to better screen high-risk patients for intervention, thereby improving clinical efficacy.

摘要

为探讨多参数流式细胞术(MFC)和实时定量聚合酶链反应(RQ-PCR)检测微小残留病(MRD)在造血干细胞移植(HSCT)前对预测费城染色体阳性急性淋巴细胞白血病(Ph(+) ALL)复发、无白血病生存(LFS)和总生存(OS)的不同价值。进行了一项回顾性研究(n = 280)。采用多参数流式细胞术和RQ-PCR测定MRD。移植前BCR-ABL融合转录本的MFC和RQ-PCR MRD分析显示出很强的相关性。移植前MFC和RQ-PCR检测到的MRD阳性率分别为25.7%(72/280)和60.7%(170/280)。MFC MRD阳性(MRDpos)的Ph(+) ALL患者3年累积复发率(CIR)高于MFC MRD阴性(MRDneg)的Ph(+) ALL患者(23.6%对8.6%;P<0.001)。然而,RQ-PCR MRDpos组与RQ-PCR MRDneg组的3年OS、LFS和非复发死亡率相似。此外,与RQ-PCR MRD<1%组相比,RQ-PCR MRD≥1%的患者3年CIR更高(23.1%对11.4%;P = 0.032),LFS更低(53.8%对74.4%;P = 0.015),OS更低(57.7%对79.1%;P = 0.009)。多因素分析证实MFC MRD状态和RQ-PCR MRD≥1%与预后相关(P<0.05)。MFC检测MRD预测复发的敏感性、特异性、阳性预测值(PPV)和阴性预测值(NPV)分别为48.50%、77.56%、23.62%和87.16%。此外,当用RQ-PCR MRD≥1%预测复发时,敏感性、特异性、PPV和NPV分别为23.00%、88.59%、17.15%和91.84%。另外,当用移植前MRD阳性状态(MFC MRDpos或RQ-PCR MRD≥1%)预测移植后复发时,敏感性、特异性、PPV和NPV分别为54.29%、73.88%、45.7%和91.87%。移植前MFC和RQ-PCR检测MRD水平均可预测接受异基因HSCT的Ph(+) B-ALL患者的预后。移植前MFC MRD阳性状态是移植后白血病复发的危险因素。两种方法联合使用(MFC MRDpos或RQ-PCR MRD≥1%)可提高预测复发的敏感性、PPV和NPV,并有助于更好地筛选高危患者进行干预,从而提高临床疗效。

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