Background/aim: Chimeric antigen receptor (CAR) T-cell therapy is increasingly utilized not only in adults but also in pediatric cases of B cell acute lymphoblastic leukemia (ALL-B). However, following CAR T-cell therapy, serious side effects such as neurotoxicity, known as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), can occur due to the actions of inflammatory cytokines and immune effector cells, leading to damage to the blood-brain barrier. While systemic steroid therapy is commonly used to treat ICANS, the effectiveness of alternative treatments is limited due to the blood-brain barrier. Recently, reports have suggested the effectiveness of administering intrathecal (IT) steroid to ICANS patients. Therefore, our institution aims to report a case of administering intrathecal steroids to a Grade IV ICANS patient.
Case report: Here, we describe a case of a patient with ALL-B successfully treated with IT steroid for CD19 CAR T-cell therapy-associated grade IV ICANS. Following two isolated central nervous system (CNS) relapses of ALL-B at the age of 6, the boy underwent allogeneic hematopoietic stem cell transplantation. Subsequently, relapses occurred in the CNS and chest wall mass, leading to the administration of CAR T-cell therapy. Prior to CAR T-cell therapy, the patient received six doses of IT chemotherapy (methotrexate, cytarabine, hydrocortisone) following leukapheresis, followed by CAR T-cell infusion at a dose of 4.74×106/kg.
Five days post-CAR T-cell infusion, the patient developed fever and hypotension, prompting initiation of intravenous tocilizumab, followed by seizures necessitating IV dexamethasone and antiepileptic drug (AED) administration. Despite these interventions, seizures persisted, leading to respiratory arrest and subsequent intubation for transfer to the intensive care unit (ICU). Brain MRI at the time revealed increased T2 signal of the thalami and pons, as well as multifocal cortical lesions with diffusion restriction.
The administration of IV dexamethasone was maintained for one day, but with intermittent seizure spikes observed on electroencephalography (EEG) and no improvement in ICANS, IT steroid (hydrocortisone, 30mg) was administered. The following day, EEG showed improvement in seizure spikes, prompting reduction in AED dosage, which continued for approximately five days. Spontaneous breathing improved, leading to extubation, and the patient was transferred to the ward on the seventh day of IT steroid administration.
Conclusion: Based on this case, it was observed that administering IT steroids to steroid-refractory ICANS patients was effective. However, long-term follow-up observation of this patient is necessary, and further research on a larger scale of patients will be needed.