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造血干细胞移植后患者血浆巨细胞病毒DNA拷贝数与巨细胞病毒病的关系
引用本文:陈育红,赵晓甦,刘开彦,许兰平,刘代红,陈欢,张晓辉,韩伟,王昱,赵婷,黄晓军,赵晓涛.造血干细胞移植后患者血浆巨细胞病毒DNA拷贝数与巨细胞病毒病的关系[J].中华医学杂志,2009,89(22).
作者姓名:陈育红  赵晓甦  刘开彦  许兰平  刘代红  陈欢  张晓辉  韩伟  王昱  赵婷  黄晓军  赵晓涛
作者单位:1. 北京大学人民医院血液病研究所,100044
2. 北京大学人民医院血液病研究所检验科,100044
基金项目:国家高技术研究发展计划(863计划),首都医学发展科研基金 
摘    要:目的 评价实时定量聚合酶链式反应(RQ-PCR)法监测造血干细胞移植后患者血浆巨细胞病毒(CMV)DNA水平的临床意义.方法 对2005年1月至2007年1月之间进行异基因造血干细胞移植的318例患者,自移植应采用RQ-PCR每周监测血浆CMV-DNA水平,6×102拷贝/ml视为CMV-PCR阳性.结果 共136例患者(42.8%)检测出1025例次血浆CMV-DNA阳性,首次阳性出现的中位时间为42 d,最高拷贝数及初始拷贝数中位值分别为1.5×104拷贝/ml和4.5×103拷贝/ml.318例患者中共发生CMV肺炎及肠炎23例,累积发病率为7.2%.14例患者在发生CMV病之前出现CMV血症,4例在出现临床表现后方检测出病毒阳性,另有5例CMV血症阴性的患者诊断为CMV疾病.发生CMV病的患者其CMV-DNA最高拷贝数高于未发生组患者(4.3×104拷贝/ml比1.3×104拷贝/ml,P=0.009),但初始拷贝数差异无统计学意义(3.7×103拷贝/ml比4.7×103拷贝/ml,P=0.63).CMV-DNA最高拷贝数随着发生CMV感染的次数增加而增高,在发生CMV感染1~4次的患者中,中位数值分别为82.6×102、261.3×102、440.8×102和10 659.0×102拷贝/ml(P<0.01),且CMV肺炎及CMV肠炎发病率也从2.7%(5/182)明显上升至50%(2/4)(P=0.001).结论 采用RQ-PCR法监测造血干细胞移植后患者血浆CMV-DNA水平对CMV病的发生有一定的预测意义,高CMV-DNA拷贝数及多次感染者预示着CMV病发生概率升高.

关 键 词:造血干细胞移植  聚合酶链反应  巨细胞病毒

Relationship between copies of cytomegalovirus in plasma and cytomegalovirus disease after allogenetic hematopoeitic stem cell transplantation
CHEN Yu-hong,ZHAO Xiao-su,LIU Kai-yan,XU Lan-ping,LIU Dai-hong,CHEN Hu-an,ZHANG Xiao-hui,HAN Wei,WANG Yu,ZHAO Ting,ZHAO Xiao-tao,HUANG Xiao-jun.Relationship between copies of cytomegalovirus in plasma and cytomegalovirus disease after allogenetic hematopoeitic stem cell transplantation[J].National Medical Journal of China,2009,89(22).
Authors:CHEN Yu-hong  ZHAO Xiao-su  LIU Kai-yan  XU Lan-ping  LIU Dai-hong  CHEN Hu-an  ZHANG Xiao-hui  HAN Wei  WANG Yu  ZHAO Ting  ZHAO Xiao-tao  HUANG Xiao-jun
Abstract:Objective To evaluate the clinical significance of using real-time quantitative polymerase chain reaction (RQ-PCR) in monitoring cytomegalovirus infection in allogenic hemapoietic stem-cell transplant (allo-HSCT) recipients. Methods A total of 318 patients who received allo-HSCT in the past 2 years were analyzed retrospectively. RQ-PCR was performed to monitor CMV viremia twice a week after transplantation. Results CMV-DNA was detected in the plasma of 136 patients. The median time for the occurrence of CMV-DNA was 42 days after HSCT. The highest CMV-DNA load was 1.5×104 copies/ml while the CMV-DNA load at onset of reactivation was 4.5×103 copies/ml. CMV pneumonia or CMV enteritis occurred in 23 patients and the incidence of these CMV diseases is 7.2%. The CMV-DNA was detectable before CMV disease among 14 patients and after the clinical manifestation of CMV disease in 4 patients, while 5 patients were diagnosed with CMV disease having no plasma CMV-DNA positive at all. The highest CMV-DNA load was higher in the CMV patients than those with no CMV disease (4.3×104 copies/ml and 1.3×104 copies/ml,P=0.009)although the initial load had no difference (3.7×103 copies/m vs 4.7×103 copies/ml, P=0.63). The highest CMV-DNA load also rose with the occurring frequency of CMV infection occurred from 1 to 4 times. The median values of CMV-DNA were 82.6×102, 261.3×102, 440.8×102 and 10 659.0×102 copies/ml (P<0.01) respectively. Meanwhile, the incidence of CMV disease also increased markedly from 2.7% (5/182)to 50%(2/4) (P=0.001). Conclusion Detection of CMV-DNA in plasma by RQ-PCR appears to be an effective prognostic predictor of CMV diseases. High CMV-DNA load and repeated viremia indicate a high incidence of CMV diseases.
Keywords:Hematopoietic stem cell transplantation  Polymerase chain reaction  Cytomegalovirus disease
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