Foscarnet against human herpesvirus (HHV)-6 reactivation after allo-SCT: breakthrough HHV-6 encephalitis following antiviral prophylaxis
Foscarnet against human herpesvirus (HHV)-6 reactivation after allo-SCT: breakthrough HHV-6 encephalitis following antiviral prophylaxis
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DOI：
10.1038/bmt.2012.121
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发表时间：
2013-02-01
影响因子：
4.8
通讯作者：
Kadota, J.
中科院分区：
文献类型：
--
作者：
Ogata, M.;Satou, T.;Kadota, J.
日本几个SCT中心最近报告了人疱疹病毒（HHV）-6脑炎的高发病率。为了评价低剂量膦甲酸（PFA）在无关BM或脐带血（CB）受者中预防HHV-6感染的效果，我们检查了未预防HHV-6（队列1，n =51）和PFA预防（队列2，PFA 50 mg/kg/天，植入后10天，n = 67）的连续队列。每周进行血浆实时PCR测定。高水平的再活化定义为HHV-6 DNA在第70天≥ 10（4）拷贝/mL，是主要终点。与队列1（33.8%，P = 0.095）相比，队列2（19.4%）中未观察到高水平再激活显著降低。在队列2中，在无关BM受体中确定了高水平HHV-6再激活较少的趋势（P = 0.067），但在CB受体中未观察到发生率差异（P = 0.75）。3例患者在PFA预防后发生了突破性HHV-6脑炎，队列1（9.9%）和队列2（4.5%，P = 0.24）之间HHV-6脑炎的发生率无差异。总之，50 mg/kg/天PFA不能有效抑制HHV-6再活化，也不能预防所有HHV-6脑炎病例。为了有效预防HHV-6脑炎，可能需要基于HHV-6脑炎发病机制的替代方法。骨髓移植（2013）48，257-264; doi：10.1038/bmt.2012.121; 2012年7月2日在线发表
High incidences of human herpesvirus (HHV)-6 encephalitis have recently been reported from several Japanese SCT centers. To evaluate the effect of low-dose foscarnet (PFA) in preventing HHV-6 infection among recipients of unrelated BM or cord blood (CB), we examined consecutive cohorts without prophylaxis against HHV-6 (Cohort 1, n =51) and with PFA prophylaxis (Cohort 2, PFA 50 mg/kg/day for 10 days after engraftment, n = 67). Plasma real-time PCR assay was performed weekly. High-level reactivation defined as HHV-6 DNA >= 10(4) copies/mL by day 70 was the primary endpoint. No significant reduction of high-level reactivation was seen in Cohort 2 (19.4%) compared with Cohort 1 (33.8%, P = 0.095). A trend was identified toward fewer high-level HHV-6 reactivations in Cohort 2 among recipients of unrelated BM (P = 0.067), but no difference in incidence was observed among CB recipients (P = 0.75). Breakthrough HHV-6 encephalitis occurred following PFA prophylaxis in three patients, and incidence of HHV-6 encephalitis did not differ between Cohort 1 (9.9%) and Cohort 2 (4.5%, P = 0.24). In conclusion, 50 mg/kg/day of PFA does not effectively suppress HHV-6 reactivation and cannot prevent all cases of HHV-6 encephalitis. To effectively prevent HHV-6 encephalitis, alternative approaches based on the pathogenesis of HHV-6 encephalitis will probably be required. Bone Marrow Transplantation (2013) 48, 257-264; doi:10.1038/bmt.2012.121; published online 2 July 2012