CASE REPORT article
Front. Hematol.
Sec. Immunobiology and Immunotherapy
Volume 4 - 2025 | doi: 10.3389/frhem.2025.1628552
This article is part of the Research TopicNovel Insights into CAR T-cell Associated Neurotoxicity - Volume IIView all articles
Case report: Severe HHV-6-related encephalitis following anti-CD19 CAR-T therapy: No evidence of HHV-6 reactivation in transduced CAR-T cells
Provisionally accepted
Nina Marie Birk1
Katrine Kielsen1,2*
Özcan Met3,4Eva Kannik Haastrup1
Thomas Morgan Hulen3Cecilie Ø Madsen3
Torben Barington5,6Jonas Nielsen1
Kristian Schønning1Søren Lykke Petersen1
Marianne Ifversen1- 1Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- 2University of Copenhagen, Copenhagen, Denmark
- 3Copenhagen University Hospital Herlev, Herlev, Denmark
- 4Technical University of Denmark, Kongens Lyngby, Denmark
- 5Odense University Hospital, Odense, Denmark
- 6University of Southern Denmark, Odense, Denmark
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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.
Keywords: CAR-T therapy, HHV-6, Encephalitis, ICANS, neurotoxicity Human herpes virus 6: HHV-6 Chimeric antigen receptor T cells: CAR-T Immune effector cell-associated neurotoxicity syndrome: ICANS Cerebrospinal fluid: CSF Hematopoietic stem cell transplantation: HSCT
Received: 15 May 2025; Accepted: 08 Aug 2025.
Copyright: © 2025 Birk, Kielsen, Met, Haastrup, Hulen, Madsen, Barington, Nielsen, Schønning, Petersen and Ifversen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Katrine Kielsen, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.