AUTHOR=Birk Nina Marie , Kielsen Katrine , Met Özcan , Haastrup Eva Kannik , Hulen Thomas M. , Madsen Cecilie Ø. , Barington Torben , Nielsen Jonas , Schønning Kristian , Petersen Søren Lykke , Ifversen Marianne 

TITLE=Case Report: Severe HHV-6-related encephalitis following anti-CD19 CAR-T therapy with no evidence of HHV-6 reactivation in transduced CAR-T cells

JOURNAL=Frontiers in Hematology

VOLUME=Volume 4 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/hematology/articles/10.3389/frhem.2025.1628552

DOI=10.3389/frhem.2025.1628552

ISSN=2813-3935

ABSTRACT=We report a case of severe encephalitis caused by human herpes virus 6 (HHV-6) following CD19 chimeric antigen receptor T (CAR-T) cell therapy. Rapid expansion of circulating T-lymphocytes and high HHV-6 viral load (4,500,000 DNA copies/mL) early after CAR-T infusion suggested HHV-6 transferal from autologous CAR-T cells. To investigate this hypothesis, we retrospectively analyzed cryo-preserved patient samples for HHV-6. HHV-6 was undetectable in the apheresis product, transduced CAR-T cells, and in vitro activated CAR-T cells. In conclusion, despite strong clinical suspicion, we found no evidence to substantiate the infused CAR-T cells as the source of the severe HHV-6 infection.