Recent Advances in the Prognosis of HHV-6 Encephalitis Following Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Human herpesvirus-6 (HHV-6) encephalitis is a rare but fatal complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite advancements in transplantation outcomes and supportive care, knowledge regarding the clinical features and prognostic factors of HHV-6 encephalitis remains limited. This study aims to clarify the clinical characteristics of HHV-6 encephalitis in allo-HSCT recipients and to identify prognostic factors. This is a single-center retrospective study that analyzed the patients with HHV-6 encephalitis who underwent allo-HSCT at our institute between 2004 and 2023. The diagnosis of HHV-6 encephalitis was confirmed by the presence of neurological symptoms and the detection of HHV-6 DNA in the cerebrospinal fluid using real-time polymerase chain reaction. Fifty-three patients were included in this study. The median time from allo-HSCT to HHV-6 encephalitis onset was 24 days (range: 3 to 189). Of the 53 patients, 38 (71.7%) received systemic steroids, with a median interval of 11 days (range: 2 to 46) from steroid initiation to encephalitis onset. One-year overall survival and non-relapse mortality (NRM) after encephalitis diagnosis were 33.5% and 46.5%, respectively. While HHV-6 encephalitis directly caused one death, infections unrelated to HHV-6 were the leading cause of mortality (47.5%). The interval from the onset to the initiation of antiviral therapy was significantly shorter in recent cases (0.0 after 2018 versus 1.5 days before 2017: P = .0086), and 1-year NRM was significantly lower (26.8 versus 62.1%; P = .024). Multivariate analysis revealed that allo-HSCT before 2017 (hazard ratio [HR] 3.13, P = .012) and haploidentical transplantation (HR 3.07, P = .001) were independent prognostic factors for NRM. Among the 32 patients who survived for over 100 days after the initiation of HHV-6 encephalitis treatment, neurological sequelae persisted in 16 (50.0%) cases, including short-term memory impairment in 11. Overall, our study indicates that recent improvements in HHV-6 encephalitis outcomes after allo-HSCT likely result from earlier initiation of antiviral treatment.