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儿科造血干细胞移植受者腺病毒分子检测的危险因素。

Risk factors for molecular detection of adenovirus in pediatric hematopoietic stem cell transplantation recipients.

机构信息

Division of Cancer and Blood Disorders, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA.

出版信息

Biol Blood Marrow Transplant. 2012 Aug;18(8):1227-34. doi: 10.1016/j.bbmt.2012.01.013. Epub 2012 Jan 25.

Abstract

Adenovirus (AdV) infections are a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the use of molecular AdV testing in HSCT at our institution and identify risk factors for AdV viremia and disease, we performed a retrospective cohort study of all HSCT recipients who had undergone AdV polymerase chain reaction testing over a 2-year period. Two cohorts were identified: cohort 1, comprising patients testing positive for AdV (n = 7) and cohort 2, comprising patients testing negative (n = 36). Overall patient characteristics were not statistically significantly different between the 2 cohorts. A comparison of cohort 1 and cohort 2 identified the following medication exposures as risk factors influencing AdV status: preparatory regimens using fludarabine (relative risk [RR], 8.73; 95% confidence interval [CI], 1.18-64.27; P = .006), melphalan (RR, 3.47; 95% CI, 0.76-15.94: P = .08), and/or cyclophosphamide (RR, 0.18; 95% CI, 0.02-1.4; P = .05), and GVHD prophylaxis with methylprednisone (RR, 3.73; 95% CI, 1.01-13.9; P = .04). AdV-positive patients had higher grades of GVHD and higher rates of GVHD of the gastrointestinal tract (RR, 4; 95% CI, 1.18-13.5; P = .03) compared with AdV-negative patients. Four of the 7 AdV-positive patients had concomitant clinical manifestations of disease, including pneumonia, diarrhea, and/or disseminated disease. Clinical outcomes in symptomatic patients included resolution of disease in 2 patients and death in 2 patients. All 7 AdV-positive patients received antiviral therapy, including 1 patient with severe disseminated disease that resolved after administration of liposomal cidofovir. Our study at a large pediatric HSCT center provides important preliminary data for the development of a prospective trial destined to identify specific HCST patient subpopulations that might benefit most from molecular screening and early preemptive therapy.

摘要

腺病毒(AdV)感染是造血干细胞移植(HSCT)患者发病率和死亡率的主要原因。为了评估我们机构在 HSCT 中使用分子 AdV 检测的情况,并确定 AdV 血症和疾病的危险因素,我们对在 2 年内接受过 AdV 聚合酶链反应检测的所有 HSCT 受者进行了回顾性队列研究。确定了两个队列:队列 1,包括 AdV 检测阳性的患者(n = 7);队列 2,包括 AdV 检测阴性的患者(n = 36)。两个队列的总体患者特征在统计学上无显著差异。队列 1 和队列 2 的比较确定了以下药物暴露作为影响 AdV 状态的危险因素:使用氟达拉滨(RR,8.73;95%置信区间 [CI],1.18-64.27;P =.006)、美法仑(RR,3.47;95%CI,0.76-15.94:P =.08)和/或环磷酰胺(RR,0.18;95%CI,0.02-1.4;P =.05)的预处理方案,以及 GVHD 预防用甲基强的松龙(RR,3.73;95%CI,1.01-13.9;P =.04)。与 AdV 阴性患者相比,AdV 阳性患者的 GVHD 分级更高,胃肠道 GVHD 的发生率更高(RR,4;95%CI,1.18-13.5;P =.03)。7 名 AdV 阳性患者中有 4 名同时出现疾病的临床表现,包括肺炎、腹泻和/或播散性疾病。症状性患者的临床结局包括 2 例患者的疾病缓解和 2 例患者的死亡。所有 7 名 AdV 阳性患者均接受了抗病毒治疗,包括 1 名患有严重播散性疾病的患者,在给予脂质体更昔洛韦后疾病得到缓解。我们在一家大型儿科 HSCT 中心的研究为一项前瞻性试验提供了重要的初步数据,该试验旨在确定最有可能从分子筛查和早期预防性治疗中获益的特定 HSCT 患者亚群。

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