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Risk factors and associations with clinical outcomes of cytomegalovirus reactivation after haploidentical versus matched-sibling unmanipulated PBSCT in patients with hematologic malignancies.
Annals of Hematology ( IF 3.5 ) Pub Date : 2020-06-22 , DOI: 10.1007/s00277-020-04156-6
Xiao-Ning Gao 1 , Ji Lin 2 , Li-Jun Wang 1 , Fei Li 1 , Hong-Hua Li 1 , Shu-Hong Wang 1 , Wen-Rong Huang 1 , Chun-Ji Gao 1 , Li Yu 1 , Dai-Hong Liu 1
Affiliation  

In allogeneic hematopoietic stem cell transplantation recipients, cytomegalovirus (CMV) infection can cause overt CMV-associated disease, which is a main cause of transplantation-associated mortality. CMV infection correlates closely with donor’s type. We therefore examined whether risk factors of CMV reactivation and clinical endpoints in patients with hematologic malignancies after allogeneic peripheral blood stem cell transplantation (PBSCT) differed between using matched-sibling donors (MSD-SCT) and haploidentical donors (HID-SCT). In this retrospective cohort study, we enrolled in 200 consecutive patients received an unmanipulated G-CSF-mobilized allogeneic PBSCT. Ninety (45%) patients received MSD-SCT and 110 (55%) received HID-SCT. Quantitative PCR was used for monitoring of CMV reactivation after transplantation. One-year cumulative incidence of CMV DNAemia was 55.0%, ranging from 23.5% in MSD-SCT group to 81.0% in HID-SCT group (p < 0.001). Although univariate analyses showed that non-myeloid malignancies, disease in complete remission status at transplantation, pretreatment with antithymocyte globulin, HLA-haploidentical donors, male donors, previous Epstein-Barr virus DNAemia, and absolute lymphocyte count on day 30 < 0.6 × 109/L were respectively associated with CMV reactivation after transplantation in total cohort of recipients (all p < 0.05), haploidentical donors were found to be the only independent predictor in multivariate analyses (Hazard ratio = 6.4, p < 0.001). Furthermore, univariate analyses revealed that non-myeloid malignancies and previous Epstein-Barr virus DNAemia were respectively associated with CMV reactivation in MSD-SCT recipients, and female was associated with CMV reactivation in HID-SCT recipients (all p < 0.05). In HID-SCT recipients, but not MSD-SCT recipients, previous CMV DNAemia was associated with a lower cumulative incidence of acute graft-versus-host disease (49.2% vs. 72.6%, p < 0.001). CMV DNAemia did not play a role in the relapse rate, but it was strongly associated with an increased risk of non-relapse mortality either in total cohort of recipients (30.5% vs. 13.7%; p = 0.003) or in the HID-SCT subgroup (36.0% vs. 16.7%; p = 0.030). Relapse-free survival and overall survival in total cohort of recipients with CMV DNAemia were both inferior to those without CMV DNAemia (45.3% vs. 57.6% and 54.8% vs. 65.8%, respectively; both p < 0.05). However, in subgroup analysis according to donor’s type, neither relapse-free survival nor overall survival was impacted by CMV status (both p > 0.05). This study addressed differences in incidence, risk factors, and associations with clinical outcomes of CMV reactivation after haploidentical versus matched-sibling PBSCT.



中文翻译:

血液恶性肿瘤患者单倍性与配对兄弟未操纵PBSCT后的危险因素及其与巨细胞病毒再激活的临床结局的关系。

在同种异体造血干细胞移植受者中,巨细胞病毒(CMV)感染可引起明显的CMV相关疾病,这是与移植相关的死亡率的主要原因。CMV感染与供者的类型密切相关。因此,我们检查了异基因外周血干细胞移植(PBSCT)后血液系统恶性肿瘤患者CMV激活的风险因素和临床终点是否使用同胞同胞供体(MSD-SCT)和单倍体供体(HID-SCT)之间存在差异。在这项回顾性队列研究中,我们招募了200名连续患者,他们接受了未经操纵的G-CSF动员的同种异体PBSCT。90名(45%)患者接受了MSD-SCT,110名(55%)患者接受了HID-SCT。定量PCR用于监测移植后的CMV再活化。p  <0.001)。尽管单因素分析显示非髓样恶性肿瘤,移植时疾病完全缓解,抗胸腺细胞球蛋白,HLA单倍体供体,男性供体,先前的爱泼斯坦-巴尔病毒DNAemia的预处理以及第30天的绝对淋巴细胞计数<0.6×10 9 / L分别与受者总队列中移植后的CMV激活相关(所有p  <0.05),单倍体供体是多变量分析中唯一的独立预测因子(危险比= 6.4,p <0.001)。此外,单因素分析显示,非髓样恶性肿瘤和先前的爱泼斯坦-巴尔病毒DNA血症分别与MSD-SCT接受者的CMV激活有关,女性与HID-SCT接受者的CMV激活有关(所有p  <0.05)。在HID-SCT接受者而非MSD-SCT接受者中,先前的CMV DNA血症与急性移植物抗宿主病的累积发生率较低相关(49.2%对72.6%,p <  0.001)。CMV DNAemia在复发率中不起作用,但在接受者总队列中(30.5%vs. 13.7%;p =  0.003)或在HID-SCT中,它与非复发死亡率增加的风险密切相关。亚组(36.0%vs. 16.7%; p = 0.030)。患有CMV DNAemia的受试者的总队列的无复发存活率和总体存活率均低于没有CMV DNAemia的受试者(分别为45.3%对57.6%和54.8%对65.8%;两者均p  <0.05)。但是,在根据供体类型进行的亚组分析中,无复发生存率和总生存率均不受CMV状态的影响(均p>  0.05)。这项研究探讨了单倍性与配对同胞PBSCT后CMV再激活的发生率,危险因素以及与临床结果相关性的差异。

更新日期:2020-06-22
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