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[WT1基因检测及流式细胞术监测微小残留病在异基因造血干细胞移植治疗骨髓增生异常综合征中的临床意义]

[Clinical implication of minimal residue disease monitoring by WT1 gene detection and flow cytometry in myelodysplastic syndrome with allogeneic stem cell transplantation].

作者信息

Zhao X S, Mo X D, Hong Y, Chang Y J, Qin Y Z, Liu Y R, Chen Y Y, Zhang X H, Xu L P, Huang X J

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2018 Dec 14;39(12):998-1003. doi: 10.3760/cma.j.issn.0253-2727.2018.12.006.

Abstract

To investigate the clinical significance of minimal residual disease (MRD) monitoring by using WT1 gene and flow cytometry (FCM) in patients with myelodysplastic syndrome (MDS) who receiving allogeneic stem cell transplantation (allo-HSCT). WT1 gene and MDS-related abnormal immunophenotype were examined by real-time quantitative polymerase chain reaction (RQ-PCR) and FCM, respectively. The bone marrow samples were collected from patients with MDS who received allo-HSCT from Feb, 2011 to Oct, 2015 in Peking University People's Hospital before and after transplantation. Among 92 MDS patients, 40 (48.2%) patients were positive for WT1 (WT1(+)) and 9 (10.8%) patients were positive for flow cytometry (FCM(+)). 27 patients (29.3%) met the criteria of our combinative standard, MRDco (MRDco(+)). Only FCM(+) post-transplant (<0.001) and MRDco(+) (=0.017) were associated with relapse. The cumulative incidence of relapse (CIR) at 2 years were 66.7% and 1.2% (<0.001) in FCM(+) and FCM(-) groups. MRDco(+) group had a 2-year CIR of 23.0% while MRDco(-) group had a 2-year CIR of 1.6% (=0.004). The specificity of post-transplant WT1, FCM and MRDco to predict relapse was 59.0%, 96.4% and 74.7%, respectively. The sensitivity of these three MRD parameters to predict relapse was 66.7%. Post-transplant FCM and MRDco are useful tools to monitor MRD for MDS after transplantation. The preemptive intervention based on MRDco is able to reduce the relapse rate.

摘要

探讨采用WT1基因和流式细胞术(FCM)监测微小残留病(MRD)在接受异基因造血干细胞移植(allo-HSCT)的骨髓增生异常综合征(MDS)患者中的临床意义。分别采用实时定量聚合酶链反应(RQ-PCR)和FCM检测WT1基因及MDS相关异常免疫表型。收集2011年2月至2015年10月在北京大学人民医院接受allo-HSCT的MDS患者移植前后的骨髓样本。92例MDS患者中,40例(48.2%)WT1阳性(WT1(+)),9例(10.8%)流式细胞术阳性(FCM(+))。27例患者(29.3%)符合我们的联合标准,即MRDco(MRDco(+))。仅移植后FCM(+)(<0.001)和MRDco(+)(=0.017)与复发相关。FCM(+)组和FCM(-)组2年复发累积发生率(CIR)分别为66.7%和1.2%(<0.001)。MRDco(+)组2年CIR为23.0%,而MRDco(-)组2年CIR为1.6%(=0.004)。移植后WT1、FCM和MRDco预测复发的特异性分别为59.0%、96.4%和74.7%。这三个MRD参数预测复发的敏感性为66.7%。移植后FCM和MRDco是监测MDS移植后MRD的有用工具。基于MRDco的抢先干预能够降低复发率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd7/7348232/7d4544414baa/cjh-39-12-998-g001.jpg

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