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目的:采用联合抗病毒药物及巨细胞病毒(CMV)特异性T淋巴细胞(CMV-CTL)进行抢先抗病毒治疗,减少异基因造血干细胞移植后早期CMV疾病的发生率和病死率。方法:334例进行异基因造血干细胞移植的患者,其中同胞相合移植100例,非血缘移植88例,亲缘间半相同移植146例;移植后采用RQ-PCR方法每周检测1~2次检测血浆CMV-DNA,若>5×102拷贝数/ml为CMV血症。全部患者预处理阶段-9~-2d应用更昔洛韦预防CMV感染。抢先抗病毒治疗主要首先采用更昔洛韦(DHPG)或膦甲酸钠作为一线治疗,在一线治疗失败情况下部分患者采用联合抗病毒药物或者CMV-CTL过继细胞免疫进行挽救治疗。结果:移植后100d之内(+100d)334例患者中有231例发生CMV感染,总体累计发生率为69.10%,同胞相合移植的发生率最低33例(33.3%),明显低于非血缘移植78例(88.6%)和亲缘间半相同移植120例(82.1%)(P<0.05);在一线治疗失败的情况下,29.4%(68/231)的患者给予联合抗病毒药物治疗,12.1%(28/231)患者给予了CMV-CTL细胞治疗。93.9%(217/231)的患者经过抢先抗病毒治疗后转为阴性。CMV疾病的发生率为3.8%,病死率仅为1.7%。无论是单因素及多因素分析均表明,亲缘间半相同移植和非血缘移植,以及Ⅱ~Ⅳ急性移植物抗宿主病是CMV感染发生的高危因素。结论:allo-HSCT后通过RQ-PCR监测CMV血症并予联合抗病毒药物和CMV-CTL细胞进行抢先抗病毒治疗可以明显减少CMV疾病病死率,特别是对于接受亲缘间半相同/非血缘移植的高危患者。
OBJECTIVE: To preempt antiviral therapy with CMV-specific cytotoxic T lymphocytes (CMV-CTL) and to reduce the incidence and mortality of early CMV disease after allogeneic hematopoietic stem cell transplantation. Methods: A total of 334 patients undergoing allogeneic hematopoietic stem cell transplantation were enrolled in this study. Among them, 100 matched siblings and 88 non-blood transplanted siblings were enrolled in this study. CMV-DNA, if> 5 x 102 copies / ml is CMV-like. All patients pretreatment phase -9 ~ -2d application of ganciclovir prevent CMV infection. Pre-emptive antiviral therapy is mainly first-line treatment with ganciclovir (DHPG) or foscarnet as first-line therapy, with some antiviral drugs or CMV-CTL adoptive cell immunization in the first-line treatment failure. Results: Among the 334 patients within 100d after transplantation (+ 100d), CMV infection occurred in 231 patients, with an overall cumulative incidence of 69.10% and the lowest incidence of sibling coincidence transplantation in 33 (33.3%) patients, which was significantly lower than that of non-blood transfusion In the first-line treatment failure, 29.4% (68/231) of the patients were given combined antiviral therapy and 12.1% (28/231) patients were treated with CMV-CTL cells. 93.9% (217/231) of patients turned negative after preemptive antiviral treatment. The incidence of CMV disease was 3.8% and the case fatality rate was only 1.7%. Both univariate and multivariate analysis showed that semi-identical intercourse transplantation and non-hemophilic transplantation, and Ⅱ ~ Ⅳ acute graft-versus-host disease were risk factors for CMV infection. CONCLUSIONS: Allo-HSCT monitoring of CMV seroprevalence by RQ-PCR and preemptive antiviral treatment with antiviral agents and CMV-CTL cells can significantly reduce the mortality of CMV disease, especially for those patients who have undergone half-same / non-blood-related transplantation Of high-risk patients.