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  

Relationship between copies of cytomegalovirus in plasma and cytomegalovirus disease after allogenetic hematopoeitic stem cell transplantation

作　　者：陈育红[1] 赵晓甦[1] 刘开彦[1] 许兰平[1] 刘代红[1] 陈欢[1] 张晓辉[1] 韩伟[1] 王昱[1] 赵婷[1] 赵晓涛[2] 黄晓军[1] 

机构地区：[1]北京大学人民医院血液病研究所,100044 [2]北京大学人民医院检验科,100044

出　　处：《中华医学杂志》2009年第22期1540-1543,共4页National Medical Journal of China

基　　金：国家“863”高技术研究发展计划基金（2006AA02Z4A0）;首都医学发展科研基金（2005-1010）

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，〉6×10^2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42d，最高拷贝数及初始拷贝数中位值分别为1．5×10^4拷贝／ml和4．5×10^3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（4．3×10^4拷贝／ml比1．3×10^4拷贝／ml，P=0．009），但初始拷贝数差异无统计学意义（3．7×10^3拷贝／ml比4．7×10^3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82．6×10^2、261．3×10^2、440．8×10^2和10659．0×10^2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。Objective To evaluate the clinical significance of using real-time quantitative polymerase chain reaction （RQ-PCR） in monitoring cytomegalovirus infection in allogenie hemapoietie 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 ×10^4 copies/ml while the CMV-DNA load at onset of reactivation was 4. 5× 10^3 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 × 10^4 copies/ ml and 1.3 ×10^4 copies/ml,P =0. 009）although the initial load had no difference （3.7 × 10^3 eopies/m vs 4. 7×10^3 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 × 10^2, 261.3 ×10^2, 440. 8 ×10^2 and 10 659. 0 ×10^2 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.

关 键 词：造血干细胞移植 聚合酶链反应 巨细胞病毒 

分 类 号：R752.53[医药卫生—皮肤病学与性病学] R457.7[医药卫生—临床医学]