""Chimeric antigen receptor (CAR)-T cell therapy targeting CD19 has revolutionized the treatment of B-cell acute lymphoblastic leukemia (ALL), inducing complete remission in 70-90% of patients. CAR-T cell therapy, unfortunately, causes neurologic toxicity in approximately 40% of patients that can be life-threatening in some cases. Therefore, there is an urgency to identify immunological and brain biomarkers that predict which patients will develop severe neurotoxicity early in the course of treatment. Patients at increased risk for developing severe neurotoxicity can be monitored more closely and receive early interventions to minimize the severity of neurotoxicity. To identify immunological and brain predictors and mediators of neurotoxicity, we are conducting a longitudinal, prospective study and recruiting consecutive patients who are eligible to receive CAR-T cell therapy. We have enrolled 12 patients and aim to enroll at least 3 more patients over the next few months. We are collecting peripheral blood (PB) samples, multimodal brain MRI, and neuropsychological assessments at: (i) baseline before lymphodepleting chemotherapy, (ii) post-infusion day 10, and (iii) post-infusion day 28. We have processed MRI data, which showed that MRI-derived brain measures deviated away from baseline values by post-infusion day 10 and, subsequently, most reverted back to baseline values by post-infusion day 28. PB samples have been frozen and stored at -80ºC. This project is a new research direction where we will immunophenotype stored PB samples using CyTOF (cytometry by time-of-flight) to understand whether changes in immune cell profiles are associated with changes in brain structure, function, and metabolism. The preliminary information generated in this project will refine aims and develop hypotheses in an NIH-funded, definitive study of 80 patients and 40 matched controls. The biomarkers identified in the larger study will guide future research into early interventions that minimize neurotoxicity without interfering with the efficacy of CAR-T cell therapy.""

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