抢先治疗减少异基因造血干细胞移植后早期巨细胞病毒疾病的临床研究

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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.
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