干扰素α-2b治疗慢性粒细胞性白血病的前瞻性随机对照研究  

Comparison of therapeutic effects of low-dose versus high-dose interferon α-2b treatment on chronic myelocytic leukemia: a prospective randomized study

作　　者：杜金伟[1] 朱平[1] 田丁[2] 董作仁[3] 杨淑莲[4] 李松波[4] 唐亚辉[5] 刘辉[6] 岑溪南[1] 张英[1] 朱强[1] 祝毓琳[1] 杨英[1] 王东侠[4] 王昭[7] 崔华[7] 马一盖[8] 陈文明[9] 刘复强[10] 马键[11] 王景文[12] 沈悌[13] 达万明[14] 

机构地区：[1]北京大学第一医院,100034 [2]北京市宣武医院 [3]河北医科大学第二附属医院 [4]河北省廊坊市中医院 [5]海军总医院 [6]北京医院 [7]北京友谊医院 [8]卫生部中日友好医院 [9]首都医科大学朝阳医院 [10]北京同仁医院 [11]解放军第三○四医院 [12]北京军区总医院 [13]北京协和医院 [14]解放军总医院

出　　处：《中华医学杂志》2005年第19期1305-1309,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30470739);教育部博士点基金资助项目(20030001017);北京自然科学基金资助项目(7032028)

摘　　要：目的比较高、低剂量干扰素(IFN)α2b治疗慢性粒细胞性白血病(CML)的效果。方法建立检测融合基因bcr abl的荧光实时定量逆转录聚合酶链反应(RQ PCR)方法,观察治疗后融合基因表达水平的变化。选择30例临床初诊的CML患者随机分为两组,先服用羟基脲控制外周血白细胞达20×109/L以下,然后分别给予IFNα2b300万IU隔日皮下注射(3MIU组)和500万IU每周6次(5MIU组)皮下注射,治疗3～6个月,每月抽取骨髓标本,检测融合基因bcr abl的表达情况。结果RQ PCR的灵敏度达50拷贝bcr abl;分别取1×103拷贝/μl和1×107拷贝/μlbcr abl质粒,以及1例CML患者的cDNA同时作8管平行扩增bcr abl融合基因,批内变异系数分别为2.35%、1.48%和1.17%,不同批次之间以K562细胞cDNA作重复性分析,批间变异系数为5.13%;CML初诊患者bcr abl/GAPDH水平介于0.010～5.799,中位值为0.098;治疗3个月后3MIU组和5MIU组患者骨髓bcr abl水平平均下降19%和24%,两组比较差异无统计学意义(P=0.398),但是3MIU组副作用相对较小。结论RQ PCR监测融合基因bcr abl表达可以有效观察CML患者使用IFN的治疗效果;不同CML患者白血病细胞的bcr abl表达水平有较大差异;隔日3MIUIFN皮下注射治疗即可有效抑制CML白血病细胞的增殖,且副作用较小。Objective To compare the therapeutic effects of low-dose and high-dose interferon α-2b (IFN) treatment on chronic myelocytic leukemia (CML). Methods A real-time quantitative reverse transcriptase PCR (RQ-PCR) method was established to detect the fusion gene bcr-abl expression, thereby studying the reduction of leukemic cells. Thirty newly diagnosed CML patients, 21 males and 9 females, aged 14~69, were treated with hydroxyurea to keep the white blood cell count less than 20×109/L, and then randomized into 2 groups: high-dose IFN group receiving IFN α-2b 5MIU 6 times per week for 3~6 months and low-dose IFN group receiving IFN α-2b 3MIU every other day for 3~6 months. Bone marrow was collected every month to Real-time PCR was used to detect the expression of bcr-abl mRNA. Mononuclear cells were isolated and RNA was extracted to detect the expression of fusion gene bcr-abl and a control gene GAPDH. The results were reported as the number of bcr-abl copies/GAPDH copy. Results^The established real-time quantitative PCR method could detect the bcr-abl molecules as low as 50 copies. The intra-assay coefficient of variation (CV) was less than 5% and the inter-assay CV was 5.13%. The median bcr-abl fusion gene expression level of 30 CML patients before IFN therapy was 0.098 (range: 0.010～5.799). The bcr-abl expression level decreased by 19.37% and 24.86% in the low-dose and high-dose IFN groups respectively after 3 months′ therapy. No significant difference was observed between the two groups (P=0.398). Relatively more side effects were observed in the high-dose IFN group than in low-dose group. Conclusion RQ-PCR is a reliable method to monitor CML therapy by analyzing fusion gene bcr-abl expression. There is a difference in bcr-abl fusion gene expression levels among the newly diagnosed patients, and low-dose IFN is as effective as high-dose IFN in reducing bcr-abl expression but with less side effects.

关 键 词：干扰素Α-2B 治疗 慢性粒细胞性白血病 前瞻性随机对照研究 

分 类 号：R733.72[医药卫生—肿瘤]