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巨细胞病毒抢先治疗策略在不同类型造血干细胞移植中的疗效比较

来源:中国造血干细胞捐献者资料库北京管理中心 时间:2015-11-11

赵晓甦 许兰平 刘代红 陈育红 陈欢 张晓辉 韩伟 王昱 刘开彦 黄晓军

【摘要】 

目的 对不同类型异基因造血干细胞移植(HSCT)的巨细胞病毒(CMV)感染患者采用统一的抢先治疗指征,比较抗病毒治疗的效果,从而评价抢先治疗策略的临床应用价值。

方法 进行异基因HSCT患者318例,自移植后采用实时定量聚合酶链式反应法(RQ-PCR)监测血浆CMV-DNA水平,其中136例出现CMV感染,全相合HSCT 31例,亲缘半相合HSCT 88例,非血缘HSCT 17例。三种类型移植采用相同的抗病毒抢先治疗指征,比较CMV-DNA拷贝数的转阴率、CMV病的发生率及患者的长期生存率。

结果 136例CMV感染患者分别采用更昔洛韦(DHPG)、膦甲酸钠或缬更昔洛韦进行抗病毒抢先治疗,全相合、半相合及非血缘移植组治疗的中位时间相近,三组患者CMV-DNA最终转阴率相似(96.8%, 93.2%和88.2%),组间比较差异均无统计学意义(P >0.05)。抢先治疗后三组患者发生CMV肺炎及肠炎的比例及死于CMV病几率的差异也无统计学意义(P >0.05)。各类型移植患者的长期生存率差异无统计学意义(P =0.88),发生II~IV度aGVHD患者生存率明显低于0~I度急性移植物抗宿主病(aGVHD)患者(P =0.036)。

结论 不同类型造血干细胞移植术后的CMV感染患者,采用基于RQ-PCR监测的抢先治疗策略可达到相同的疗效。

 

【关键词】  血液病;造血干细胞移植;巨细胞病毒;抢先治疗 
 

 

The comparative study on the curative effect of cytomegalovirus preemptive therapy in various kinds of hemapoietic stem-cell transplantation ZHAO Xiao-su, XU Lan-ping, LIU Dai-hong, CHENG Yu-hong, CHEN Huan, ZHANG Xiao-hui, HAN Wei, WANG Yu, LIU Kai-yan, HUANG Xiao-jun. Peking University Institute of Hematology & Peking University People’s Hospital, Beijing 100044, China 
Corresponding author: HUANG Xiao-jun, Email: xjhrm@medmail.com.cn

【Abstract】 

Objective  Coherent preemptive therapy criterion were applied in various kinds of allogenic hemapoietic stem-cell transplant (allo-HSCT) recipients with cytomegalovirus (CMV) infection in order to evaluate its clinical value in various kinds of HSCT.

Methods A total of 318 allo-HSCT patients were monitored for CMV infection. Real-time quantitative polymerase chain reaction (RQ-PCR) was performed to serially monitor CMV viremia after transplantation. There are 136 patients infected with CMV including 31 of HLA-matched sibling, 88 of HLA-mismatched related and 17 of unrelated donor HSCT. Coherent preemptive therapy criterionwas employed. The clearance rate of DNAemia, the incidence of CMV disease and overall survival rate were compared in the three types of HSCT.  

Results 136 patients with CMV DNAemia were treated with ganciclovir, foscarnet and valganciclovir, respectively. The period of treatment and the clearance rate of DNAemia were comparable in HLA-matched, HLA-mismatched related and unrelated donor HSCT groups (96.8%, 93.2% and 88.2%)(P >0.05). The incidence of CMV pneumonia and CMV enteritis and overall survival rate among the three groups were similar and there was no significant difference in the proportion of patients dying of CMV diseases(P >0.05). However, the overall survival rate of the patients with II-IV acute graft-versus-host disease (aGVHD) was much lower than that of the patients with 0-I aGVHD.

Conclusion The similar curative effect could be observed when preemptive therapy was applied in various kinds of allo-HSCT recipients with cytomegalovirus infection based on the results of RQ-PCR. 
Key words】  Hematologic diseases; Hematopoietic stem cell transplantation; Cytomegalovirus; Preemptive therapy

  巨细胞病毒(CMV)感染是造血干细胞移植(HSCT)后常见的并发症,通过监测CMV感染,争取早期诊断和抢先治疗(preemptive therapy)可降低CMV病的发生率和死亡率。近年来实时RQ-PCR逐渐成为CMV感染监测的主要方法之一,国外许多研究指出CMV病的发生与病毒负荷量呈正相关。但不同类型的移植患者免疫抑制的程度有所不同,那么对CMV感染患者采用抢先治疗后疗效是否会有差异呢?目前国内尚无相关研究,国外也缺乏大宗病例的报道和明确的结论。我们对不同类型的HSCT患者采用了统一的CMV抢先治疗指征,通过对全相合、亲缘半相合及非血缘移植的CMV感染患者进行分析,比较了统一的抢先治疗策略指导下各类型移植抗病毒用药的情况、疗效以及患者长期生存率等指标,评价了CMV抢先治疗策略在不同类型HSCT中的临床应用价值。

资料和方法

1.对象:病例为本所2005年1月至2007年1月之间进行的异基因造血干细胞移植患者共 318例, 男223例,女95例,中位年龄33(5~59)岁,其中急性淋巴细胞白血病(ALL) 69例,急性髓性白血病(AML) 82例,急性双表型白血病2例,慢性髓性白血病(CML)131例,慢性粒单细胞白血病3例,骨髓增生异常综合征 15例, 非霍奇金淋巴瘤5例, 多发性骨髓瘤 3例, 重症再生障碍性贫血5例,骨髓纤维化3例。同胞全相合移植160例,亲缘半相合移植患者127例,非血缘移植患者31例。发生II~IV度aGVHD患者91例。

 

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