地西他滨治疗骨髓增生异常综合征及相关肿瘤的疗效预测因素研究  

Predict response to decitabine in patients with myelodysplastic syndrome and related neoplasms

作　　者：赵佑山[1] 郭娟[1] 许峰[1] 吴东[1] 吴凌云[1] 宋陆茜[1] 肖超[1] 李晓[1] 常春康[1] Zhao Youshan Guo Juan Xu Feng Wu Dong Wu Lingyun Song Luxi Xiao Chao Li Xiao Chang Chunkang(Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People＇s Hospital, Shanghai 200233, Chin)

机构地区：[1]上海交通大学附属第六人民医院血液科,200233

出　　处：《中华血液学杂志》2017年第2期124-128,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（81400090、81570108）

摘　　要：目的探索预测骨髓增生异常综合征（MDS）及相关肿瘤地西他滨治疗反应的临床及分子学指标。方法回顾性分析109例接受地西他滨治疗的MDS及相关肿瘤患者临床资料，采用二代测序检测MDS常见突变基因的突变情况，分析患者临床特征及基因突变与地西他滨临床反应的关系。结果地西他滨中位疗程数为4（2～11）个，共74例（67．9％）患者获得治疗反应，其中30例（27．5％）获得完全缓解（CR）；35例（32．1％）患者无反应。单因素分析结果显示，国际预后积分系统（IPSS）中危2＋高危、复杂核型、单体核型、7号染色体异常及1个疗程后PLT倍增的患者可获得更高的CR率。66．7％（14／21）的复杂核型患者、58．8％（10／17）的单体核型患者及66．7％（10／15）的TP53基因突变患者获得CR；TP53基因突变常合并复杂核型及单体核型；多因素分析显示TP53突变、1个疗程后PLT倍增及复杂核型是预测地西他滨治疗获得CR的独立预后因素，其中TP53突变是最强的预测因子（OR=4．39，905％CI1．20～16．06，P=0．026）。结论TP53基因突变、1个疗程后PLT倍增及复杂核型可预测地西他滨完全缓解。Objective To identify clinical and molecular signatures for predicting response to decitabine （DAC） in patients with myelodysplastic syndrome （MDS） and related neoplasms. Methods The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment. Results Of 109 MDS and related neoplasms patients, there were 70 males and 39 females, the median age was 61 years old（ranges： 17-85 years old）. According to the international prognostic scoring system （IPSS）, 46 cases were included in the relatively low risk group （low risk and intermediate-1 risk）, 63 in the relative high risk group （intermediate-2 and high risk）. There were 21 cases with complex karyotype, 17 chromosome 7 abnormality and 17 monosomal karyotype. The median courses of DAC treatment was 4（2-11 ）. A total of 74 patients achieved response（67.9%） and 30（27.5%） achieved complete response（CR）. Univariate analysis found that CR was higher in patients with high risk of IPSS, complex karyotypes, monosomal karyotypes, chromosome 7 abnormality, and platelet doubling after one cycle of DAC treatment. Patients with TP53 gene mutation were more likely to receive CR, 10 of 15 patients with TP53 mutations achieved CR. （66.7%）, which was significantly higher than that of the patients without TP53 gene mutation （21.3%） （P=0.001）. Multivariate analysis showed that TP53 gene mutation, platelet doubling after one cycle of DAC treatment and the complex karyotype were independent prognostic factors for CR. Of them, TP53 gene mutation is the strongest predictor （OR=4.39, 95%CI, 1.20- 16.06, P=0.026）. Conclusion TP53 mutation, platelet doubling after one cycle of DAC treatment and complex karyotypes could predict CR to DAC.

关 键 词：骨髓增生异常综合征 地西他滨 突变 治疗结果 

分 类 号：R551.3[医药卫生—血液循环系统疾病]