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
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.
Authors
- Eva Haastrup
- Thomas Morgan Hulen (ORCID: https://orcid.org/0000-0003-2475-6526)
- Katrine Kielsen (ORCID: https://orcid.org/0000-0002-7167-012X)
- Torben Barington (ORCID: https://orcid.org/0000-0001-6968-148X)
- Kristian Schønning (ORCID: https://orcid.org/0000-0001-7767-305X)
- Jonas Vestergaard Nielsen (ORCID: https://orcid.org/0000-0001-8800-5073)
- Marianne Ifversen (ORCID: https://orcid.org/0000-0002-2558-1935)
- Charlotte Madsen (ORCID: https://orcid.org/0009-0001-2562-531X)
- Özcan Met (ORCID: https://orcid.org/0000-0002-1379-2647)
- Søren Lykke Petersen
- Nina Marie Birk (ORCID: https://orcid.org/0000-0002-6806-0910)
Institutions
- University of Copenhagen (DK)
- University of Southern Denmark (DK)
- Odense University Hospital (DK)
- Herlev Hospital (DK)
- Copenhagen University Hospital (DK)
- Rigshospitalet (DK)
- IT University of Copenhagen (DK)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Frontiers in Hematology
- Published
- 2025-09-19
- DOI
- https://doi.org/10.3389/frhem.2025.1628552
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Børnecancerfonden
- Novo Nordisk
- Faculty of Health and Medical Sciences, University of Western Australia
- Novo Nordisk Fonden
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet