EBMT Consensus: Viral CNS Infections After HSCT and CAR T-Cell Therapy

Viral central nervous system (CNS) infections—including encephalitis, meningitis, and myelitis—represent rare but severe complications after autologous or allogeneic hematopoietic cell transplantation (HSCT) and chimeric antigen receptor (CAR) T-cell therapy, carrying a 30% to 60% mortality rate and frequent neurological sequelae. To address diagnostic delays, underreporting, and practice heterogeneity driven by an absence of harmonized definitions, the EBMT Practice Harmonization and Guidelines Committee developed consensus recommendations via systematic literature review and multidisciplinary expert consensus following EBMT methodology.

The committee proposes standardized diagnostic categories defining proven and probable viral encephalitis, meningitis, and myelitis. These categories are supported by a unified diagnostic algorithm incorporating clinical evaluation, neuroimaging, electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, and targeted virological testing. Recommended initial CSF multiplex PCR panels target neurotropic pathogens, specifically human herpesvirus 6 (HHV-6), herpes simplex virus 1 and 2 (HSV-1/2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, polyomaviruses BK and JC, and selected community-acquired respiratory viruses including enterovirus 71 (EV71). The guidance emphasizes initiating prompt, risk-based empirical antiviral therapy upon clinical suspicion, while noting that many recommendations rely on expert opinion and limited observational evidence, highlighting the need for prospective studies.