Brain MRI changes in children and young adults with B-cell acute lymphoblastic leukemia following chimeric antigen receptor T-cell therapy.

Objective: To evaluate brain MRI findings in children and young adults after chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoid leukemia (B-ALL) and associate results with clinical and neurological symptoms.

Methods: We reviewed pre- and post-CAR-T cell therapy brain MRIs of B-ALL patients aged 25 years or younger who underwent therapy between April 2015 and October 2023 at a single institution. MRI abnormalities were categorized as no change, exacerbation of preexisting lesion, or newly developed lesion. Clinical CAR-mediated toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) grades, were recorded. Patients were grouped into those with and without 'exacerbated/new lesion,' and clinical and neurological symptoms were compared using Fisher's exact test.

Results: Sixteen patients with pre- and post-CAR brain MRIs (median age 16 years [interquartile range, 11-21]; 9 males, 7 females) were included in the analysis. Post-CAR brain abnormalities were observed in 81% (13/16) of patients, including white matter (WM) signal changes (12/16), leptomeningeal enhancement (1/16), and cerebellar embolic infarction (1/16). Of the post-CAR WM lesions, 50% (6/12) were exacerbated, 33% (4/12) were newly developed, and 17% (2/12) remained unchanged compared to pre-CAR brain MRI. No difference in CRS (p = 0.079) or ICANS grades (p > 0.99) was observed between patients with and without 'exacerbated/new lesions'.

Conclusion: Children and young adults with B-ALL can develop brain MRI abnormalities after CAR T-cell therapy, predominantly WM signal changes. These brain abnormalities did not show an association with higher CRS or ICANS grade.

Key points: Question Brain MRI findings after chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoid leukemia (B-ALL) and their association with clinical and neurological symptoms are not well understood. Findings Brain MRI abnormalities, mostly white matter changes, were seen in 81% of patients but were not associated with CAR-mediated toxicities. Clinical relevance Brain MRI abnormalities, commonly observed post-CAR T-cell therapy, do not correlate with the severity of CAR-related toxicities, aiding in the clinical management and monitoring of these patients.