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.

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.
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DOI:
10.3389/fonc.2021.700234
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发表时间:
2021
影响因子:
4.7
通讯作者:
Wu D
Wu D
中科院分区:
医学3区
文献类型:
--
作者:
Hou C;Zhou L;Yang M;Jiang S;Shen H;Zhu M;Chen J;Miao M;Xu Y;Wu D

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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)患者来说,高复发率仍然是一个主要问题。我们用突变(MUT)和流式细胞术(FCM)分析了115例MDS患者接受allo-HSCT的临床结果与微小残留病(MRD)的相关性。我们根据分子遗传学和FCM MRD结果将115例MDS患者在HSCT后30天分为四组。FCM高MUTpos组和低MUTneg组的两年无进展生存率(PFS)分别为20%和79%(P<0.001)。此外,通过单因素分析发现,移植前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)、修订的国际预后评分系统(IPSS-R)细胞遗传学风险差(HR,4.906;P<0.001)是PFS的不良危险因素。多因素分析发现,移植前IPSS-R评分≥4(HR,4.488;P=0.015)、DNMT3A基因突变(HR,2.385;P=0.049)、FCM MRD阳性和第30天持续性基因突变(HR,5.198;P=0.013)是影响疾病进展的独立危险因素。总之,我们的数据表明,用FCM监测MRD并结合第30天的基因突变清除可以帮助预测移植后MDS患者的疾病进展。
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 FCMhigh MUTpos and FCMlow MUTneg 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.
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