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[供体巨细胞病毒血清学状态对异基因干细胞移植结局的影响]

[The effect of donor cytomegalovirus serological status on the outcome of allogeneic stem cell transplantation].

作者信息

Liu J, Fu Q, Wang Y, Wang F R, Han W, Ma Y R, Yan C H, Han T T, Wang J Z, Wang Z D, Zhang X H, Xu L P, Liu K Y, Huang X J, Sun Y Q

机构信息

Department of Hematology, Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2021 May 1;60(5):459-465. doi: 10.3760/cma.j.cn112138-20200714-00668.

Abstract

Donor cytomegalovirus (CMV) serological negative status may have an adverse effect on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), while there is inadequate data for Chinese people. This study is to explore the impact of donor CMV serological status on the outcome of CMV seropositive patients receiving allo-HSCT. Our study retrospectively analyzed 16 CMV seropositive patients with hematological malignancies receiving allogeneic grafts from CMV seronegative donors (antibody IgG negative) at Peking University People's Hospital from March 2013 to March 2020, which was defined as D/R group. The other 64 CMV seropositive patients receiving grafts from CMV seropositive donors at the same period of time were selected as matched controls through a propensity score with 1∶4 depending on age, disease state and donor-recipient relationship (D/R group). Patients in D/R group developed CMV DNAemia later than patients in the D/R group (+37 days vs. +31 days after allo-HSCT, =0.011), but the duration of CMV DNAemia in D/R group was longer than that of D/R group (99 days vs. 34 days, =0.012). The rate of CMV reactivation 4 times or more in D/R group was 4/16, significantly higher than that of D/R group (4.7%, 3/64, =0.01). The incidences of refractory CMV DNAemia (14/16 vs. 56.3%, =0.021) and CMV disease (4/16 vs. 4.7%, =0.01) in D/R group were both higher than those in D/R group. In addition, the application of CMV-CTL as the second-line antiviral treatment in D/R group was more than that in D/R group. Univariate analysis and multivariate analysis suggested that CMV serological negativity is an independent risk factor for refractory CMV DNAemia and the duration of CMV infection. The cumulative incidence of aGVHDⅡ-Ⅳ, cGVHD, 3-year probability of NRM, overall survival, and the cumulative incidence of relapse were all comparable in two groups. Although there is no significant effect on OS and NRM, the incidence of refractory CMV DNAemia, the frequency of virus reactivation, and the development of CMV disease in D/R group are higher than those in controls. Therefore, CMV seropositive donors are preferred for CMV seropositive patients.

摘要

供者巨细胞病毒(CMV)血清学阴性状态可能会对异基因造血干细胞移植(allo-HSCT)的结局产生不利影响,而针对中国人的数据尚不充分。本研究旨在探讨供者CMV血清学状态对接受allo-HSCT的CMV血清学阳性患者结局的影响。我们的研究回顾性分析了2013年3月至2020年3月期间在北京大 学人 民医院接受来自CMV血清学阴性供者(抗体IgG阴性)异基因移植物的16例血液系统恶性肿瘤CMV血清学阳性患者,将其定义为D/R组。同期接受来自CMV血清学阳性供者移植物的另外64例CMV血清学阳性患者根据年龄、疾病状态和供受者关系按1∶4的倾向评分进行匹配作为对照(D/R组)。D/R组患者发生CMV血症的时间晚于D/R组患者(allo-HSCT后+37天对+31天,P=0.011),但D/R组CMV血症持续时间长于D/R组(99天对34天,P=0.012)。D/R组CMV再激活4次及以上的发生率为4/16,显著高于D/R组(4.7%,3/64,P=0.01)。D/R组难治性CMV血症(14/16对56.3%,P=0.021)和CMV疾病(4/16对4.7%,P=0.01)的发生率均高于D/R组。此外,D/R组中应用CMV-CTL作为二线抗病毒治疗的情况多于D/R组。单因素分析和多因素分析表明,CMV血清学阴性是难治性CMV血症和CMV感染持续时间的独立危险因素。两组中急性移植物抗宿主病Ⅱ-Ⅳ级、慢性移植物抗宿主病、3年非复发死亡率概率、总生存率以及复发累积发生率均相当。虽然对总生存率和非复发死亡率无显著影响,但D/R组难治性CMV血症的发生率、病毒再激活频率以及CMV疾病的发生均高于对照组。因此,CMV血清学阳性患者优先选择CMV血清学阳性供者。

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