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

Biol Blood Marrow Transplant. 2018 Jun;24(6):1264-1273. doi: 10.1016/j.bbmt.2018.02.008. Epub 2018 Feb 15.

Abstract

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 ≥ 104 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.

Keywords: Acute GVHD; Foscarnet; HHV-6 encephalitis; Human herpesvirus-6; Prophylaxis.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • DNA, Viral / blood
  • Encephalitis, Viral / drug therapy
  • Encephalitis, Viral / prevention & control*
  • Female
  • Fetal Blood / transplantation
  • Foscarnet / pharmacology*
  • Foscarnet / therapeutic use
  • Graft vs Host Disease
  • Herpesvirus 6, Human / drug effects*
  • Historically Controlled Study
  • Humans
  • Middle Aged
  • Myeloablative Agonists / pharmacology
  • Premedication / methods
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome
  • Virus Activation / drug effects*
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Myeloablative Agonists
  • Foscarnet