中国全科医学 ›› 2023, Vol. 26 ›› Issue (11): 1361-1368.DOI: 10.12114/j.issn.1007-9572.2022.0661

• 论著 • 上一篇    下一篇

整合流式评分在骨髓增生异常综合征中的诊断和预后价值研究

陈颖1, 李纪鹏1,*(), 叶佩佩2   

  1. 1.315040 浙江省宁波市,宁波大学附属人民医院中心实验室
    2.315040 浙江省宁波市,宁波大学附属人民医院血液科
  • 收稿日期:2022-10-14 修回日期:2022-12-11 出版日期:2023-04-15 发布日期:2023-01-03
  • 通讯作者: 李纪鹏
  • 陈颖,李纪鹏,叶佩佩.整合流式评分在骨髓增生异常综合征中的诊断和预后价值研究[J].中国全科医学,2023,26(11):1361-1368.[www.chinagp.net]

    作者贡献:陈颖进行文章的构思与设计,文章的可行性分析,负责收集病例、数据整理分析及论文撰写;李纪鹏负责研究指导、论文修改及经费支持,并对文章整体负责、监督管理;叶佩佩负责收集病例、临床指导。
  • 基金资助:
    国家自然科学基金资助项目(81872433); 宁波市医学科技计划项目(2020Y45)

Diagnostic and Prognostic Values of Integrated Flow Cytometric Score in Myelodysplastic Syndrome

CHEN Ying1, LI Jipeng1,*(), YE Peipei2   

  1. 1. Department of Central Laboratory, the Affiliated People's Hospital of Ningbo University, Ningbo 315040, China
    2. Department of Hematology, the Affiliated People's Hospital of Ningbo University, Ningbo 315040, China
  • Received:2022-10-14 Revised:2022-12-11 Published:2023-04-15 Online:2023-01-03
  • Contact: LI Jipeng
  • About author:
    CHEN Y, LI J P, YE P P. Diagnostic and prognostic values of integrated flow cytometric score in myelodysplastic syndrome [J]. Chinese General Practice, 2023, 26 (11): 1361-1368.

摘要: 背景 诊断骨髓增生异常综合征(MDS)的"金标准"是基于骨髓形态、祖细胞计数和细胞遗传学。但发育不良并非MDS特有,骨髓涂片质量不佳、病态造血不明显或原始细胞无显著增加,尤其是在核型正常的情况下,MDS诊断通常很有挑战性。多参数流式细胞术(MFC)已成为诊断MDS的重要共同标准。有研究认为整合流式评分(iFS)是MFC诊断MDS的最佳评分系统,但在中国人群中的研究鲜见报道。 目的 本研究探索iFS在MDS诊断和预后评估中的应用前景,旨在为临床诊断MDS和评价预后寻找合适的流式细胞术评分系统。 方法 回顾性分析2019年1月至2022年4月在宁波大学附属人民医院血液科诊治的83例MDS患者(MDS组)和77例非MDS患者(非MDS组)的免疫表型,以MDS组中骨髓原始细胞比例小于5%为低级别MDS,包括MDS伴单系病态造血(MDS-SLD)、MDS伴多系病态造血(MDS-MLD),MDS伴环形铁粒幼细胞(MDS-RS)、MDS无法分类(MDS-U)、MDS伴孤立5q-(MDS-5q-)。收集MDS组患者染色体核型结果和骨髓形态学结果。根据iFS判读表型异常,比较两组患者各细胞系出现表型异常的概率;绘制iFS和Ogata评分诊断MDS的受试者工作特征(ROC)曲线,计算灵敏度、特异度和ROC曲线下面积(AUC)等;采用Spearman秩相关分析MDS患者iFS评价等级与细胞遗传学风险分类、修订版国际预后积分系统(IPSS-R)的相关性;应用Kaplan-Meier法绘制MDS(iFS评价为C)的患者和其他MDS(iFS评价为A或B)患者的无事件生存曲线,生存曲线比较采用Log-rank检验。 结果 MDS组髓系祖细胞、粒系和/或单核系、红细胞出现表型异常比例分别为71.1%、73.5%和60.2%,高于非MDS组(1.3%、18.8%和14.2%)(P<0.05)。iFS诊断MDS的AUC为0.921〔95%CI(0.876,0.967)〕,特异度为93.5%,灵敏度为81.9%,诊断低级别MDS、核型正常的低级别MDS灵敏度分别为66.7%和65.0%。iFS评价等级与IPSS-R呈正相关(rs=0.411,P<0.05),iFS评价为MDS的患者无事件生存期短于其他MDS患者(χ2=5.71,P<0.05)。 结论 iFS可弥补形态学和细胞遗传学的局限,有效诊断MDS和评估其预后,为临床医生提供MDS诊断和预后信息。

关键词: 骨髓增生异常综合征, 流式细胞术, 整合流式评分, 诊断, 预后, 免疫表型分型

Abstract:

Background

The diagnostic gold standard for myelodysplastic syndrome (MDS) is based on bone marrow morphology, progenitor cell count and cytogenetics. But the dysplasia is not specific for MDS. In the context of poor quality of bone marrow smear, very mildmorbid hematopoiesis, insignificant increase in blasts, especially a normal karyotype, the diagnosis of MDS is often challenging. Multiparameter flow cytometry has become a key tool for the diagnosis of MDS. Some studies have shown that integrated flow cytometric score (iFS) is the best scoring system for MDS diagnosis, but its use has not been reported in Chinese population.

Objective

To assess diagnostic and prognostic values of iFS in MDS to demine whether it is an appropriate flow cytometry scoring system for clinical diagnosis and prognosise valuation of MDS.

Methods

The immunophenotype data of 83 patients with MDS and 77 patients with non-MDS treated in Department of Hematology, the Affiliated People's Hospital of Ningbo University between January 2019 and April 2022 were analyzed retrospectively. Low-grade MDS was defined as less than 5% blasts in bone marrow, including MDS with single lineage dysplasia, MDS with multilineage dysplasia, MDS with ring sideroblasts, MDS, unclassifiable, and MDS with isolated del (5q). The results of chromosome karyotype and bone marrow morphology of MDS patients were collected. The probability of phenotypeabnormalities in each cell lineinterpreted according to the iFS was compared between MDS and non-MDS patients. ROC analysis was conducted to assess the performance of iFS and Ogata score in diagnosing MDS, with sensitivity, specificity and the area under the ROC curve (AUC) calculated. In the MDS group, the Spearman's rank correlation was adopted to analyze the correlation of iFS grade with cytogenetic risk category and Revised International Prognostic Scoring System (IPSS-R). The event-free survival curve was plotted by the Kaplan-Meier method and compared between MDS patients diagnosed by the iFS and the other MDS patients by Log-rank test.

Results

MDS group had higher prevalence of phenotype abnormalities of myeloid progenitors (71.1% vs 1.3%), granulocytes/monocytes (73.5% vs 18.8%) and erythrocytes (60.2% vs 14.2%) than non-MDS group (P<0.05). The specificity and sensitivity of iFS for the diagnosis of MDS was 93.5% and 81.9%, with an AUC of 0.921〔95%CI (0.876, 0.967) 〕. And its sensitivities in diagnosing low-grade MDS and low-grade MDS with normal karyotype were 66.7% and 65.0%, respectively. The iFS grade was positively correlated with IPSS-R (rs=0.411, P<0.05). The event-free survival of MDS patients diagnosed by the iFS was shorter than that of the other MDS patients (χ2=5.71, P<0.05) .

Conclusion

The iFS may compensate for morphological and cytogenetic limitations, effectively diagnose MDS and assess its prognosis, and provide clinicians with diagnostic and prognostic information on MDS.

Key words: Myelodysplastic syndromes, Flow cytometry, Integrated flow cytometric score, Diagnosis, Prognosis, Immunophenotyping