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布林西多福韦作为挽救疗法用于控制造血干细胞移植儿科受者的腺病毒血症

Brincidofovir as a Salvage Therapy in Controlling Adenoviremia in Pediatric Recipients of Hematopoietic Stem Cell Transplant.

作者信息

Meena Jagdish P, Phillips Robert S, Kinsey Sally

机构信息

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Centre for Reviews and Dissemination, University of York, York.

出版信息

J Pediatr Hematol Oncol. 2019 Oct;41(7):e467-e472. doi: 10.1097/MPH.0000000000001480.

DOI:10.1097/MPH.0000000000001480
PMID:30969265
Abstract

Adenovirus infection is a well-known complication in patients receiving hematopoietic stem cell transplantation (HSCT). Brincidofovir (BCV) is an orally bioavailable lipid conjugate of cidofovir, which has activity against adenoviruses. We present a review of adenovirus infections treated with BCV which were unresponsive to cidofovir initially in 4 patients and it was used upfront in one patient. Children with adenovirus infection following HSCT treated with BCV, between July 2014 and February 2018 were recognized. Five patients including 3 male and 2 female with a median age of 10 years (range, 2.2 to 10 y) were identified. The median days of adenoviremia detection was 18 days (range, 7 to 303 d) posttransplant. The median peak viral load by quantitative polymerase chain reaction was 21,38,000 copies/mL (range, 1,77,200 to 31,97,000 copies/mL). The median time from first detection of adenoviremia to become negative was 30 days (range, 15 to 113 d). The sites involved were gastrointestinal tract in all patients and 2 patients had additional respiratory tract involvement. Two patients survived and 3 patients died of sepsis. All patients responded well to BCV and no adverse effect was noticed. We saw the good safety profile and excellent antiadenoviral activity of BCV in pediatric patients receiving HSCT without the nephrotoxicity and it may have a role in preemptive therapy.

摘要

腺病毒感染是接受造血干细胞移植(HSCT)患者中一种众所周知的并发症。布林西多福韦(BCV)是西多福韦的口服生物可利用脂质共轭物,对腺病毒具有活性。我们对4例最初对西多福韦无反应而用BCV治疗以及1例一开始就使用BCV治疗的腺病毒感染进行了综述。识别出2014年7月至2018年2月期间接受BCV治疗的HSCT后腺病毒感染的儿童。确定了5例患者,包括3名男性和2名女性,中位年龄为10岁(范围2.2至10岁)。移植后腺病毒血症检测的中位天数为18天(范围7至303天)。通过定量聚合酶链反应检测的病毒载量峰值中位数为2138000拷贝/mL(范围177200至3197000拷贝/mL)。从首次检测到腺病毒血症至转阴的中位时间为30天(范围15至113天)。所有患者受累部位均为胃肠道,2例患者还累及呼吸道。2例患者存活,3例患者死于败血症。所有患者对BCV反应良好,未观察到不良反应。我们看到BCV在接受HSCT的儿科患者中具有良好的安全性和出色的抗腺病毒活性,且无肾毒性,它可能在抢先治疗中发挥作用。

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