CAR-T Cell Therapy-Related Neurotoxicity in Pediatric Acute Lymphoblastic Leukemia: Spectrum of Imaging Findings

Pediatr Neurol. 2020 Oct:111:51-58. doi: 10.1016/j.pediatrneurol.2020.06.014. Epub 2020 Jul 3.


The emergence of CD19-targeted chimeric antigen receptor-T (CAR-T) cell therapy has created a new era in the management of pediatric patients with refractory B-cell malignancies such as B-cell acute lymphoblastic leukemia. Immune effector cell-associated neurotoxicity syndrome (ICANS) is frequently encountered in the postinfusion period of CD19-targeted chimeric antigen receptor-T cell therapy and in some cases may be fatal. Knowledge related to the spectrum of imaging findings of CD19-targeted CAR-T cell therapy-related ICANS is, however, still very much lacking, underscoring the need for continued research in this area. In this review, we hope to provide an overview of current knowledge and provide an in-depth literature review related to this topic. A brief discussion of possible imaging differential diagnoses, specifically in children with acute lymphoblastic leukemia, will also be included. Illustrative cases for each imaging phenotype will be provided to facilitate a better understanding. A greater level of insight of the spectrum of imaging findings related to ICANS will improve patients' management and enhance efforts to safely deliver CAR-T cell immunotherapy. It will also facilitate further studies to derive mechanistic insights of ICANS and potentially assist in the testing and monitoring of therapeutic interventions.

Keywords: Acute lymphoblastic leukemia; CAR-T cell therapy; ICANS; Imaging; Magnetic resonance imaging (MRI).

Publication types

  • Review

MeSH terms

  • Brain Diseases / diagnostic imaging
  • Brain Diseases / etiology*
  • Brain Diseases / pathology*
  • Child
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Neurotoxicity Syndromes / diagnostic imaging
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell*
  • Receptors, Chimeric Antigen*


  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen