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Researchers at Children's Hospital of Philadelphia Reveal New Insights into Non-Inflammatory Causes of Rare Neurological Symptoms in Children, Adolescents and Young Adults Following CAR-T Therapy

Thursday, September 26, 2024 Child Health News
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PR Newswire

PHILADELPHIA, Sept. 26, 2024

Study marks the first time these side effects were reported in children

PHILADELPHIA, Sept. 26, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) revealed for the first time that children, adolescents and young adults may experience very rare neurological issues of paraparesis and quadriparesis following chimeric antigen receptor T-cell (CAR-T) therapy, a type of immunotherapy used to treat B-cell Acute Lymphoblastic Leukemia (B-ALL). Additionally, these complications occurred without the type of inflammation typically seen in adults. The findings were published today in the journal Blood.
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Researchers previously reported that CAR-T may lead to complications known as immune effector cell-associated neurotoxicity syndrome (ICANS), which can present with a range of neurological symptoms from mild confusion to severe issues such as brain swelling, seizures and coma. However, as CAR-T therapy becomes a more prevalent cancer treatment, new patterns are emerging, revealing complex side effects in younger patients.
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"Our findings suggest CAR-T induced neurological side effects, while rare, can impact a spectrum of age ranges, from children to young adults. The causes of these complications in young people could be more complex than the exclusive T-cell activation and excessive cytokine production that typically leads to inflammation in adults," said Caroline Diorio, MD, FRCPC, FAAP, an attending physician with CHOP's Cancer Center. "The lack of inflammation points to a host of other underlying culprits, such as metabolic profiles, that require extensive additional research to understand."

In this study, Diorio and her team analyzed two children, two teenagers and one young adult who developed severe muscle weakness, either in all four limbs (quadriparesis) or the lower half of their body (paraparesis) after receiving an infusion of either CD19- or CD22-directed CAR-T therapy to treat B-ALL. All but one of the five patients died during the study due to their cancer.

The researchers performed detailed examinations on all five patients, such as tests on spinal fluid, and protein analysis to understand the response. They also later performed full autopsies on two of the deceased patients. Overall, they found chronic damage to white matter in the brain, but without the usual inflammatory responses. The children also had lower levels of certain inflammatory chemicals compared to those who did not have severe symptoms.

"I can't emphasize enough that for most patients, immunotherapy, such as CAR-T, is a lifesaver," said Diorio, who is also an Assistant Professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine. "However, these study findings empower us to understand the rare instances when it's not effective and take prompt action to address that."

The study was supported by the ACC K12 Award, a CIHR Fellowship Award and a CHOP Cell and Gene Therapy Award. The authors would like to gratefully acknowledge the assistance of the Translational and Correlative Studies Laboratory at the University of Pennsylvania.

Diorio et al. "Quadriparesis and paraparesis following chimeric antigen receptor T-cell (CAR-T) therapy in children and adolescents." Online September 26, 2024. Blood. DOI: 10.1182/blood.2024023933.

About Children's Hospital of Philadelphia:A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.

Contact: Jennifer LeeChildren's Hospital of Philadelphia(267) [email protected]

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SOURCE Children's Hospital of Philadelphia
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