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造血干细胞移植后单个核细胞EBV-DNA定量监测预测移植后淋巴增殖性疾病
引用本文:王莉红,任汉云,孙玉华,邱志祥,岑溪南,欧晋平,许蔚林,王茫桔,王文生,李渊,董玉君,尹玥,梁赜隐.造血干细胞移植后单个核细胞EBV-DNA定量监测预测移植后淋巴增殖性疾病[J].中华血液学杂志,2010,31(2).
作者姓名:王莉红  任汉云  孙玉华  邱志祥  岑溪南  欧晋平  许蔚林  王茫桔  王文生  李渊  董玉君  尹玥  梁赜隐
作者单位:北京大学第一医院血液科,100034
摘    要:目的 应用定量PCR方法 监测造血干细胞移植(HSCT)后单个核细胞EBV含量,评估其临床效果.方法 51例HSCT患者从预处理阶段开始,采用荧光定量PCR方法 每周1次检测外周s血单个核细胞EBV-DNA拷贝数,分析EBV再活化的影响因素以及EBV-DNA拷贝数与发生淋巴增殖性疾病(PTLD)的相关性.结果 51例患者EBV血症累积发生率为58.8%,HSCT后EBV感染的时间晚于CMV感染分别为(39.6±23.5)d和(25.0±15.1)d,P<0.01].Allo-HSCT中HLA不合患者EBV血症的累积发生率显著高于HLA相合患者(分别为93.3%和48.1%,P<0.01),应用ATG组显著高于无ATG组(分别为92.3%和18.7%,P<0.01),年龄<20岁组患者显著高于≥20岁组(分别为100%和53.1%,P<0.01).30例患者中4例(13.3%)EBV血症发展为EBV-PTLD,均为持续2周以上EBV-DNA>106拷贝/ml的患者(13例中4例).PTLD患者的中位生存时间为19.5(11~75)d.结论 HSCT后EBV活化比率高,尤其是在HLA不相合供者、应用ATG和年龄<20岁的患者,有必要常规进行单个核细胞EBV-DNA检测.Allo-HSCT患者在EBV-DNA拷贝数>106拷贝/ml,尤其是持续2周以上者,易进展为PTLD,应给予抢先治疗.

关 键 词:造血干细胞移植  聚合酶链反应  疮疹病毒4    淋巴组织增殖性疾病

Quantitative monitoring of mononucleated cell Epstein-Barr virus (EBV)-DNA for predicting EBV associated lymphoproliferative disorders after stem cell transplantation
WANG Li-hong,REN Han-yun,SUN Yu-hua,QIU Zhi-xiang,CEN Xi-nan,OU Jin-ping,XU Wei-lin,WANG Mang-ju,WANG Wen-sheng,LI Yuan,DONG Yu-jun,YIN Yue,LIANG Ze-yin.Quantitative monitoring of mononucleated cell Epstein-Barr virus (EBV)-DNA for predicting EBV associated lymphoproliferative disorders after stem cell transplantation[J].Chinese Journal of Hematology,2010,31(2).
Authors:WANG Li-hong  REN Han-yun  SUN Yu-hua  QIU Zhi-xiang  CEN Xi-nan  OU Jin-ping  XU Wei-lin  WANG Mang-ju  WANG Wen-sheng  LI Yuan  DONG Yu-jun  YIN Yue  LIANG Ze-yin
Abstract:Objective To monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopeietic stem cell transplantation (HSCT) and to evaluate its implication.Methods EBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT.Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed.Results The cumulative incidence of EBV viremia was 58.8%.EBV reactivation occurred (39.6±23.5) days after HSCT,later than that of cytnmegalovirus (CMV) reactivation (25.0±15.1) days (P<0.01).HLA mismatch (P<0.01),use of antithymocyte globulin (ATG) (P<0.01),age less than twenty(P<0.001)were factors for EBV reactivation,(93.3%vs 48.1%,92.3% vs 18.7%,and 100% vs 53.1%,respectively).EBV related post-transplant lymphoproliferative disorders (EBV-PTLD) occurred only in 4 out of 30 (13.3%)EBV reactivation patients,whose EBV DNA load maintained over 106 copies/ml for at least two weeks(4 out of 13 cases).The median survival time of EBV-PTLD patients was 19.5 (11-75)days.Conclusions EBV reactivation occurs frequently after HSCT,especially in those received HLA mismatch grafts,used antithymocyte globulin or aged under twenty.Patients with EBV loads over 106 copies/ml,especially lasting over two weeks,appear to have an increased risk for PTLD,and pre-emptive therapy may be of clinical useful.
Keywords:Hematopoietic stem cell transplantation  Polymerase chain reaction  Herpesvirus 4  huamn  Lymphoproliferative disease
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