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[成人原发性骨髓增生异常综合征巢式病例对照研究队列的建立及与骨髓增生异常综合征向白血病演变相关危险因素的研究]

[Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia].

作者信息

Ma Yan, Chen Bo-Bin, Wang Xiao-Qin, Xu Xiao-Ping, Lin Guo-Wei

机构信息

Department of Hematology, Huashan Hospital, Fudan Universtiy, Shanghai, 200040, China.

Department of Hematology, Huashan Hospital, Fudan Universtiy, Shanghai, 200040, China. E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015 Dec;23(6):1638-46. doi: 10.7534/j.issn.1009-2137.2015.06.021.

Abstract

OBJECTIVE

To establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort.

METHODS

All patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models.

RESULTS

A total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model showed that the age, sex, WHO subtype, IPSS cytogenetic subgroup and bone marrow blast were independent risk factors for LFS.

CONCLUSION

A nested case-control study cohort of MDS patients is established. The clinical characteristics and WHO subtype of MDS patients in Chinese Shanghai are different from that in Western countries. The independent risk factors for MDS evolution are age, sex, WHO subtype, IPSS cytogenetic subgroup and bone marrow blast percentage.

摘要

目的

在骨髓增生异常综合征(MDS)患者中建立巢式病例对照研究队列,并调查该队列中MDS进展为白血病的临床特征、世界卫生组织(WHO)亚型及危险因素。

方法

选取2003年6月至2007年4月间由上海24家医院提供的、年龄≥18岁且初始临床表现符合造血异常的所有患者作为本研究的纳入对象。每位患者均应在基线时提供血液和骨髓样本。根据WHO分类标准,结合形态学、免疫表型、细胞遗传学和分子特征进行诊断。采用常规G显带核型分析和荧光原位杂交(FISH)技术进行细胞遗传学分析。采用Kaplan-Meier法估计累积进展风险。通过单因素Log-rank法和多因素Cox比例风险模型评估预后因素。

结果

共435例患者被诊断为MDS。MDS发病的中位年龄为58(18 - 90)岁,男性患者248例,女性患者187例(男∶女 = 1.33∶1)。多系发育异常的难治性血细胞减少症(RCMD)病例所占比例最高(65.5%),而难治性贫血(RA)(2.3%)、伴有环形铁粒幼细胞的难治性贫血(RARS)(1.1%)和5q综合征(0.5%)的比例较低。三体8(+8)是最常见的染色体异常(71例,12.7%)。平均随访时间为20.3(4.2 - 57.1)个月。随访结束时进展的患者为病例组,未进展的患者为对照组。病例组包括41例患者,对照组包括342例患者。单因素分析显示,年龄、性别、WHO亚型、白细胞计数、绝对中性粒细胞计数(ANC)、国际预后评分系统(IPSS)细胞遗传学亚组、IPSS分组和骨髓原始细胞百分比是无白血病生存(LFS)的显著危险因素。COX模型多因素分析显示,年龄、性别、WHO亚型、IPSS细胞遗传学亚组和骨髓原始细胞是LFS的独立危险因素。

结论

建立了MDS患者的巢式病例对照研究队列。中国上海MDS患者的临床特征和WHO亚型与西方国家不同。MDS进展的独立危险因素为年龄、性别、WHO亚型、IPSS细胞遗传学亚组和骨髓原始细胞百分比。

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