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

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 ≥ 10 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.

Human herpesvirus‐6B infection in pediatric allogenic hematopoietic stem cell transplant patients: Risk factors and encephalitis

“…It is well known that CBT is a risk factor for post-transplant HHV-6B encephalitis, 44 but none of the 61 CBT patients without prophylactic or preemptive antiviral treatments for HHV-6 infection developed encephalitis in this study. Although prophylactic or preemptive antiviral treatments have previously been administered to reduce the risk of post-transplant HHV-6B encephalitis in adult CBT patients, 26,45 the present data raise doubts about similar interventions for all pediatric CBT patients. One study showed that the incidence of HHV-6B encephalitis declined after the introduction of prophylactic ganciclovir treatment in pediatric CBT patients;…”

HHV-6 and septic shock: Tenuous proof of causation

“…Although herpesvirus reactivation has been associated with mortality in various patient groups, clinical trials involving liver transplant and HCT patients that have studied HHV-6 antiviral prophylaxis or a preemptive strategy (using antivirals or immunosuppression reduction) have not demonstrated clinical effectiveness (even when HHV-6 reactivation is reduced). 2,5,6 Moreover, no high-quality data support the use of antiviral treatment for HHV-6-associated syndromes. New approaches, including characterizing host responses to viral infections in immunocompromised hosts, are needed to help us better determine causality.…”

Human herpesvirus 6 encephalitis in patients administered mycophenolate mofetil as prophylaxis for graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation

“…There was no difference in the virological response to antiviral treatment between the CBT and non‐CBT cases. Moreover, efficacious strategies for prevention of HHV‐6 encephalitis have not yet been established …”