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

Transpl Infect Dis. 2019 Feb;21(1):e13024. doi: 10.1111/tid.13024. Epub 2018 Nov 27.

Abstract

Background: Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition.

Methods and results: We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis.

Conclusions: Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

Keywords: HHV-6; allogeneic hematopoietic stem cell transplantation; encephalitis; mycophenolate mofetil.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Calcineurin Inhibitors / adverse effects
  • Cord Blood Stem Cell Transplantation / adverse effects
  • Encephalitis, Viral / diagnosis
  • Encephalitis, Viral / drug therapy
  • Encephalitis, Viral / epidemiology*
  • Encephalitis, Viral / virology
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / surgery
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 6, Human / isolation & purification
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Immunosuppression Therapy / methods
  • Immunosuppressive Agents / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects*
  • Retrospective Studies
  • Roseolovirus Infections / diagnosis
  • Roseolovirus Infections / drug therapy
  • Roseolovirus Infections / epidemiology*
  • Roseolovirus Infections / virology
  • Severity of Illness Index
  • Transplantation, Homologous / adverse effects
  • Young Adult

Substances

  • Antiviral Agents
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Mycophenolic Acid

Supplementary concepts

  • Human Herpesvirus 6 encephalitis