A comparative study of the curative effects of cytomegalovirus preemptive therapy in various kinds of hematopoietic stem-cell transplantation

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(RQ)-PCR法监测血浆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、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%,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度急性移植物抗宿主病(aGVHD)患者生存率明显低于0～Ⅰ度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.Coherent preemptive therapy criterion was applied in various kinds of allogenic hematopoietic stem-cell transplant (allo-HSCT) recipients with cytomegalovirus (CMV) infection in order to evaluate its clinical value in various kinds of HSCT.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 were 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 criterion was employed. The clearance rate of DNAemia, incidence of CMV disease and overall survival rate were compared among the three types of HSCT.All the 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 among the 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.Similar curative effect can be observed when preemptive therapy is applied in various kinds of allo-HSCT recipients with cytomegalovirus infection based on the results of RQ-PCR.国家高技术研究发展计划(863计划); 国家杰出青年科学基金; 教育部创新团队支持计划PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)06476-4804