Molecular monitoring and stepwise preemptive therapy for Epstein-Barr virus viremia after allogeneic stem cell transplantation
Molecular monitoring and stepwise preemptive therapy for Epstein-Barr virus viremia after allogeneic stem cell transplantation
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同种异体干细胞移植后EB病毒血症的分子监测和逐步抢先治疗
DOI：
10.1002/ajh.23452
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发表时间：
2013-07-01
影响因子：
12.8
通讯作者：
Huang, Xiaojun
中科院分区：
文献类型：
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作者：
Liu, Qifa;Xuan, Li;Huang, Xiaojun
EB病毒（EBV）相关疾病的最佳抢先治疗仍在讨论中。根据EBV病毒血症的持续时间和病毒载量的变化，我们开发了一种针对EBV病毒血症的分步抢先治疗（抗病毒药物和减少免疫抑制剂[RI]，然后是利妥昔单抗）。应用实时定量聚合酶链反应技术对251例异基因造血干细胞移植受者的外周血EBV-DNA含量进行定期监测。EBV病毒血症和EBV相关疾病的3年累积发病率分别为31.1%+/- 3.1%和15.6%+/-2.5%，随着主要危险因素的增加而急剧上升。在64例接受第一步先占的患者中，24例达到完全缓解（CR），40例无缓解，包括25例进展为EBV相关疾病。抗病毒药物治疗有效率为2/16，RI加抗病毒药物治疗有效率为22/48（P=0.017）。15例接受利妥昔单抗预先治疗的患者中，14例达到CR，1例进展为淋巴组织增生性疾病。在26例在抢先治疗期间进展为EBV相关疾病的患者中，23例使用利妥昔单抗治疗的患者中有20例获得CR。RI联合抗病毒药物的预防效果与主要危险因素的数量相关（rs=-0.298; P=0.04）。利妥昔单抗预处理的患者B细胞重建明显延迟至少6个月。在第一步治疗和利妥昔单抗抢先治疗取得有效进展的患者中，疱疹病毒感染的风险相似（P=0.094）。低危患者应优先使用RI联合抗病毒药物治疗，高危患者应加强EBV-DNA监测，早期使用利妥昔单抗。Am.血液学杂志88：550-555，2013. (c)2013 Wiley Periodicals，Inc.
The optimal preemptive therapy for Epstein-Barr virus (EBV)-associated diseases remains under discussion. We developed a stepwise preemptive therapy (antiviral agents and reduction of immunosuppressants [RI] followed by rituximab) for EBV viremia, based on duration of EBV viremia and changes of viral loads. The blood EBV-DNA loads were regularly monitored by quantitative real-time polymerase chain reaction in 251 recipients undergoing allogeneic stem cell transplantation. The 3-year cumulative incidence of EBV viremia and EBV-associated diseases were 31.1%+/- 3.1% and 15.6%+/- 2.5%, which rose steeply with greater numbers of major risk factors. Of the 64 patients undergoing first-step preemption, 24 achieved complete response (CR) and 40 showed no response, including 25 progressing to EBV-associated diseases. The effective rates of antiviral agents and RI plus antiviral agents were 2/16 and 22/48 (P=0.017). Fourteen achieved CR and one progressed to lymphoproliferative disease in the 15 patients undergoing rituximab preemption. Of the 26 patients progressing to EBV-associated diseases during preemptive therapy, 20 obtained CR in the 23 cases with rituximab-based treatments. The preemptive efficacy of RI plus antiviral agents was correlated with the numbers of major risk factors (rs=-0.298; P=0.04). B-cell reconstitution was significantly delayed for at least 6 months in patients with rituximab preemption. The risk of herpesvirus infection was similar in patients who showed effective progress to first-step and rituximab preemption (P=0.094). RI plus antiviral agents could be given priority to low-risk patients, whereas more frequent monitoring of blood EBV-DNA and earlier preemptive rituximab should be advocated in high-risk patients. Am. J. Hematol. 88:550-555, 2013. (c) 2013 Wiley Periodicals, Inc.