Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients: A Prospective Multicenter Trial with an Historical Control Group
Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients: A Prospective Multicenter Trial with an Historical Control Group
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DOI：
10.1016/j.bbmt.2018.02.008
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发表时间：
2018-06-01
影响因子：
4.3
通讯作者：
Fukuda, Takahiro
中科院分区：
文献类型：
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作者：
Ogata, Masao;Takano, Kuniko;Fukuda, Takahiro
脐带血移植（CBT）是人类疱疹病毒6型（HHV - 6）再激活和HHV - 6脑炎的一个独特风险因素。在一项前瞻性多中心试验中，我们研究了预防性膦甲酸钠（在CBT后第7天至第27天静脉输注90 mg/kg）对CBT受者中HHV - 6再激活、HHV - 6脑炎以及急性移植物抗宿主病（aGVHD）发生的影响。2014年至2016年间，57名患者被纳入膦甲酸钠预防组。将其结果与2010年至2014年间接受CBT的历史对照组（标准治疗组，n = 63）进行比较。在CBT后60天，高水平HHV - 6再激活（定义为血浆HHV - 6 DNA≥10⁴拷贝/mL）的累积发生率在膦甲酸钠预防组中显著低于标准治疗组（18.3%对57.3%，P <.001）。多变量分析显示，清髓性预处理和标准治疗是高水平HHV - 6再激活的显著风险因素。在CBT后60天，HHV - 6脑炎的累积发生率在两组之间无差异（膦甲酸钠预防组为12.4%；标准治疗组为4.9%；P =.14）。在CBT后60天，Ⅱ - Ⅳ级和Ⅲ - Ⅳ级aGVHD的累积发生率在两组之间无差异（Ⅱ - Ⅳ级aGVHD：膦甲酸钠预防组为42.0%；标准治疗组为40.5%；P =.96；Ⅲ - Ⅳ级aGVHD：膦甲酸钠预防组为14.5%；标准治疗组为14.5%；P = 1.00）。在本研究背景下，膦甲酸钠显著抑制了CBT受者的全身性HHV - 6再激活，但未能预防HHV - 6脑炎的发生。膦甲酸钠对HHV - 6再激活的抑制未显示出对aGVHD发生率有任何影响。（C）2018美国血液与骨髓移植学会
Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA >= 10(4) copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P< .001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P= .14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P = .96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD. (C) 2018 American Society for Blood and Marrow Transplantation.