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采用流式细胞术监测微小残留病:预测异基因造血干细胞移植后 ALL 患者复发的有效方法。

Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation.

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, No 11 Xizhimen South Street, Beijing, 100044, People's Republic of China.

出版信息

Ann Hematol. 2012 Feb;91(2):183-92. doi: 10.1007/s00277-011-1285-1. Epub 2011 Jun 28.

DOI:10.1007/s00277-011-1285-1
PMID:21710165
Abstract

This study evaluated the prognostic value of minimal residual disease (MRD) monitoring by four-color flow cytometry (FCM) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). MRD was examined with four-color FCM at different time points in 139 patients (including pediatric and adult patients) with ALL after allo-HSCT. Real-time quantitative polymerase chain reaction (RQ-PCR) was applied to evaluate the MRD of Philadelphia chromosome-positive ALL (Ph+ ALL) patients. Patients who were FCM-positive (FCM+) after transplantation had a lower event-free survival (EFS) of 0.54 and a higher cumulative incidence of relapse (CIR) of 0.54 compared to an EFS of 0.80 and a CIR of 0.08 in FCM-negative (FCM-) patients (EFS, p < 0.001; CIR, p < 0.001). Similar results were obtained in high-risk patients and Ph+ ALL patients. Moreover, a FCM+ status after the second month post-HSCT (defined as MRD positive) proved to be a predictor of leukemia relapse. Multivariate analysis for EFS, OS and CIR showed that MRD status after transplantation was an independent prognostic factor (p < 0.001, p = 0.013, and p < 0.001, respectively). A good correlation was found between the MRD results of FCM and RQ-PCR (n = 126 pairs, Spearman r = 0.8139, p < 0.001). MRD monitoring by four-color FCM post-transplantation is an important tool for relapse prediction in ALL patients. Prompt and appropriate pre-emptive anti-leukemia treatment could be considered based on the status of MRD after HSCT.

摘要

这项研究评估了四色流式细胞术(FCM)在接受异基因造血干细胞移植(allo-HSCT)的急性淋巴细胞白血病(ALL)患者中监测微小残留病(MRD)的预后价值。在 139 例(包括儿科和成人患者)allo-HSCT 后 ALL 患者的不同时间点,采用四色 FCM 检测 MRD。实时定量聚合酶链反应(RQ-PCR)用于评估费城染色体阳性 ALL(Ph+ ALL)患者的 MRD。移植后 FCM 阳性(FCM+)的患者无事件生存(EFS)为 0.54,累积复发率(CIR)为 0.54,而 FCM 阴性(FCM-)患者的 EFS 为 0.80,CIR 为 0.08(EFS,p < 0.001;CIR,p < 0.001)。高危患者和 Ph+ ALL 患者也得到了类似的结果。此外,HSCT 后第二个月的 FCM+状态(定义为 MRD 阳性)被证明是白血病复发的预测因素。EFS、OS 和 CIR 的多变量分析显示,移植后 MRD 状态是独立的预后因素(p < 0.001、p = 0.013 和 p < 0.001)。FCM 和 RQ-PCR 的 MRD 结果之间存在良好的相关性(n = 126 对,Spearman r = 0.8139,p < 0.001)。移植后四色 FCM 监测是预测 ALL 患者复发的重要工具。根据 HSCT 后 MRD 的状态,可以考虑进行及时和适当的预防性抗白血病治疗。

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