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清髓性异基因造血干细胞移植后,流式细胞术定义的微小残留病早期检测及基因突变清除对骨髓增生异常综合征患者的预后价值

The Prognostic Value of Early Detection of Minimal Residual Disease as Defined by Flow Cytometry and Gene Mutation Clearance for Myelodysplastic Syndrome Patients After Myeloablative Allogeneic Hematopoietic Stem-Cell Transplantation.

作者信息

Hou Chang, Zhou Lili, Yang Menglu, Jiang Shuhui, Shen Hongjie, Zhu Mingqing, Chen Jia, Miao Miao, Xu Yang, Wu Depei

机构信息

Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China.

Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.

出版信息

Front Oncol. 2021 Aug 5;11:700234. doi: 10.3389/fonc.2021.700234. eCollection 2021.

DOI:10.3389/fonc.2021.700234
PMID:34422653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8374104/
Abstract

High relapse incidence remains a major problem for myelodysplastic syndrome (MDS) patients who have received an allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We retrospectively analyzed the correlations between clinical outcomes and minimal residual disease (MRD) by using mutations (MUT) and flow cytometry (FCM) analysis of 115 MDS patients with allo-HSCT. We divided 115 MDS patients into four groups based on molecular genetics and FCM MRD results at day 30 post-HSCT. There were significant differences in the 2-year progression-free survival (PFS) between the FCM MUT and FCM MUT groups (20% vs 79%, P < 0.001). In addition, by univariate analysis, we found that an IPSS-R score ≥4 pre-HSCT (HR, 5.061; P=0.007), DNMT3A mutations (HR, 2.291; P=0.052), TP53 mutations (HR, 3.946; P=0.011), and poor and very poor revised International Prognostic Scoring System (IPSS-R) cytogenetic risk (HR, 4.906; P < 0.001) were poor risk factors for PFS. In multivariate analysis, we found that an IPSS-R score ≥ 4 pre-HSCT (HR, 4.488; P=0.015), DNMT3A mutations (HR, 2.385; P=0.049), positive FCM MRD combined with persistence gene mutations at day 30 (HR, 5.198; P=0.013) were independent risk factors for disease progression. In conclusion, our data indicated that monitoring MRD by FCM combined with gene mutation clearance at day 30 could help in the prediction of disease progression for MDS patients after transplantation.

摘要

对于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)患者而言,高复发率仍是一个主要问题。我们通过对115例接受allo-HSCT的MDS患者进行突变(MUT)和流式细胞术(FCM)分析,回顾性分析了临床结局与微小残留病(MRD)之间的相关性。我们根据HSCT后30天的分子遗传学和FCM MRD结果,将115例MDS患者分为四组。FCM MUT组和FCM MUT组之间的2年无进展生存期(PFS)存在显著差异(20%对79%,P<0.001)。此外,通过单因素分析,我们发现HSCT前国际预后评分系统修订版(IPSS-R)评分≥4(HR,5.061;P=0.007)、DNMT3A突变(HR,2.291;P=0.052)、TP53突变(HR,3.946;P=0.011)以及预后不良和预后极差的IPSS-R细胞遗传学风险(HR,4.906;P<0.001)是PFS的不良风险因素。在多因素分析中,我们发现HSCT前IPSS-R评分≥4(HR,4.488;P=0.015)、DNMT3A突变(HR,2.385;P=0.049)、FCM MRD阳性并伴有30天时持续存在的基因突变(HR,5.198;P=0.013)是疾病进展的独立风险因素。总之,我们的数据表明,在第30天通过FCM监测MRD并结合基因突变清除情况,有助于预测MDS患者移植后的疾病进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/d57835944399/fonc-11-700234-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/cf78e266283b/fonc-11-700234-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/d1ee4ebddb28/fonc-11-700234-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/008a42e71a02/fonc-11-700234-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/d57835944399/fonc-11-700234-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/cf78e266283b/fonc-11-700234-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/d1ee4ebddb28/fonc-11-700234-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/008a42e71a02/fonc-11-700234-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b6/8374104/d57835944399/fonc-11-700234-g004.jpg

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