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

Quantitative monitoring of mononucleated cell Epstein-Barr virus （EBV） -DNA for predicting EBV associated lymphoproliferative disorders after stem cell transplantation

目的应用定量PCR方法监测造血于细胞移植（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〉10。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〉10^6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。

Objective To monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus （EBV） polymerase chain reaetion after hematopoietie stem eell transplantation （HSCT） and to evaluate its implication. Methods EBV-DNA copies of peripheral blood mononuclcated cells （PBMNCs） were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients reeeived HSCT. Correlation between development of lymphoproliferativc disorders （ LPD ） and EBV-DNA eopies and influence factors of EBV reaetivation 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 cytomcgalovirus （CMV） rcaetivation （25.0 ± 15. 1 ） days （ P 〈 0.01 ）. HLA mismateh（ 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） oeeurred only in 4 out of 30 （13.3%）EBV reaetivation patients, whose EBV DNA load maintained over 106copies/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 antithymoeyte globulin or aged under twenty. Patients with EBV loads over 10^6 eopies/ml, especially lasting over two weeks, appear to have an increased risk for PTLD, and pre-emptive therapy may be of clinical useful.