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 <Emphasis Type="BoldItalic">Question</Emphasis> 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. <Emphasis Type="BoldItalic">Findings</Emphasis> Brain MRI abnormalities, mostly white matter changes, were seen in 81% of patients but were not associated with CAR-mediated toxicities. <Emphasis Type="BoldItalic">Clinical relevance</Emphasis> 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. Graphical Abstract

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

期刊论文
发表日期：

2025年3月20日

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Hyun Gi Kim,
Kristen W. Yeom,
Iryna Vasyliv,
Zahra Shokri Varniab,
Courtney Erickson,
Christina Baggott,
Liora Michal Schultz,
Heike E. Daldrup-Link

摘要

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.

Graphical Abstract