Viral load and ganciclovir (GCV) concentration in cerebrospinal fluid of patients successfully treated with GCV or valGCV for human herpesvirus 6 encephalitis/myelitis following umbilical cord blood transplantation

Abstract

We describe successful treatment of 3 cases of human herpesvirus 6 (HHV-6) encephalitis/myelitis following cord blood transplantation (CBT). Ganciclovir (GCV) (10 mg/kg/day) reduced HHV-6 load to undetectable levels in cerebrospinal fluid (CSF). Early dose reduction in the presence of HHV-6 detectable in CSF resulted in an increased HHV-6 load. GCV was capably shifted to valganciclovir (VGCV) with an almost equivalent concentration. GCV/VGCV may be effective for HHV-6 encephalitis/myelitis after CBT, although HHV-6 load in CSF should be monitored.

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

“…As described above, various background factors are different between pediatric and adult HSCT recipients, but present study and together with the previous studies mainly analyzed adult patients suggest that there are any differences in the immune defense mechanisms for controlling HHV‐6 infection in CNS between pediatric and adult patients. In addition to the incidence, with regard to the clinical course of post‐transplant HHV‐6B encephalitis, acute limbic encephalitis is typical (Table ), and only a few pediatric patients with PALE have been reported . Thus, a meta‐analysis of large numbers of patients may help determine the precise incidence and clinical features of HHV‐6B encephalitis in pediatric HSCT patients.…”

“…A significantly higher amount of viral DNA was detected in the cerebrospinal fluid (CSF) of PALE patients than in that of HHV‐6B encephalitis patients with primary viral infection . Additionally, the fact that antiviral treatments reduce viral DNA loads in CSF suggests that viral replication in the central nervous system (CNS) occurs in the PALE patients . However, since the prognosis of PALE patients remains poor despite antiviral treatment, preemptive, and prophylactic antiviral therapies have been attempted to improve prognosis …”

“…It has been suggested that viral infection is associated with fever, 2,8 acute graft-versus-host disease (GVHD), 6,[8][9][10][11][12] engraftment delay, 6,13 and post-transplant acute limbic encephalitis (PALE). [14][15][16][17][18][19][20] Of these clinical manifestations, the strongest causal relationship has been demonstrated between viral infection and PALE. A significantly higher amount of viral DNA was detected in the cerebrospinal fluid (CSF) of PALE patients than in that of HHV-6B encephalitis patients with primary viral infection.…”

“…21 Additionally, the fact that antiviral treatments reduce viral DNA loads in CSF suggests that viral replication in the central nervous system (CNS) occurs in the PALE patients. 19,20,[22][23][24] However, since the prognosis of PALE patients remains poor despite antiviral treatment, preemptive, and prophylactic antiviral therapies have been attempted to improve prognosis. 25,26 Most HHV-6B-associated PALE patients are adults, 5,[15][16][17]20 and the previous studies examining radiological findings and treatment efficacy have been conducted in adults transplant patients.…”

Clinical characteristics and outcome of human herpesvirus-6 encephalitis after allogeneic hematopoietic stem cell transplantation

“…31,32 Antiviral CSF concentrations reach the therapeutic range in patients receiving full-dose foscarnet; 33 a case report suggested that this may not be the case in patients receiving full-dose ganciclovir. 34 Although the reasons why ganciclovir is associated with an increased risk of early death are unknown, myelosuppression owing to ganciclovir might increase the risk of infectious diseases. Combination therapy with foscarnet and ganciclovir seemed to be most effective in our study, but its evaluation is difficult because only 10 patients received the combination therapy and the doses of foscarnet and ganciclovir varied.…”