Human herpesvirus 6 (HHV-6) encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapy

Background: Human herpesvirus (HHV)-6 encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapyis relatively rare in clinical practice and needs to be differentiated from immune effector cell-associatedneurotoxicity syndrome (ICANS).

Methods: We retrospectively reported a case of HHV-6 encephalitis secondary to CAR-T cell therapy.

Results: A male patient from China with diffuse large B-cell lymphoma underwent chimeric CAR-T cell therapy anddeveloped a generalized rash on the 8^th day, followed by cognitive changes, memory loss, and disorientation onthe 14^th day after CAR-T cell therapy. Initially, ICANS was suspected. A lumbar puncture was performed on the 18^th day. The cerebrospinal fluid (CSF) analysis revealed slightly elevated protein levels and a high presence of HHV-6B sequences by mNGS. Brain MRI showed bilateral hippocampal abnormalities. The patient was ultimatelydiagnosed with HHV-6 encephalitis and treated with ganciclovir and dexamethasone. After one week of treatment,follow-up CSF analysis showed a reduction in HHV-6B sequences. The patient was discharged with improvedmemory and orientation.

Conclusion: HHV-6 encephalitis secondary to CAR-T cell therapy may be easily confused with ICANS. Timely andaggressive diagnostic procedures, such as mNGS of CSF and cranial imaging, along with prompt antiviral therapy,are crucial for improving patient outcomes.