Severe persistent neurotoxicity associated with CAR T therapy in children

Br J Haematol. 2023 Nov;203(4):651-655. doi: 10.1111/bjh.19015. Epub 2023 Aug 1.

Abstract

CD19-directed chimeric antigen receptor (CAR) T-cell therapy is an important therapy for relapsed or refractory acute lymphoblastic leukaemia, but its use carries the risk of immune effector cell-associated neurotoxicity syndrome (ICANS). In children, severe ICANS is almost universally reported in association with cytokine release syndrome and is reversible. We describe two cases of severe, intractable neurotoxicity following CAR T-cell therapy in children with pre-existing central nervous system (CNS) vulnerabilities. The cases were atypical in their delayed onset and independence from cytokine release syndrome and did not respond to standard therapies.

Keywords: CAR T-cell therapy; immune effector cell-associated neurotoxicity syndrome; immunotherapy; leukaemia; neurotoxicity.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD19 / adverse effects
  • Child
  • Cytokine Release Syndrome
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Neurotoxicity Syndromes* / etiology
  • Receptors, Chimeric Antigen*

Substances

  • cell-associated neurotoxicity
  • Receptors, Chimeric Antigen
  • Adaptor Proteins, Signal Transducing
  • Antigens, CD19