Abstract
Background
Blinatumomab, a bispecific T-cell engager that targets CD19, has emerged as a significant therapeutic option for relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). While immune effector cell-associated neurotoxicity syndrome (ICANS) is a recognized complication, most neurological adverse events are mild to moderate and generally reversible. Catastrophic and fatal neurotoxicity, however, remains exceedingly rare, particularly among pediatric patients.Case presentation
We present a case involving a 13-year-old boy diagnosed with MLL-AF4-positive precursor B-ALL who experienced catastrophic neurotoxicity during blinatumomab therapy. Following the achievement of molecular remission and successful tolerance of the first treatment cycle without neurological complications, the patient developed an abrupt-onset fever on day 13 of the second cycle. Despite the immediate discontinuation of blinatumomab and the administration of dexamethasone, his condition rapidly deteriorated, leading to confusion, refractory seizures, and coma within hours. Cranial computed tomography revealed diffuse cerebral edema with suspected subarachnoid hemorrhage and impending brain herniation. Intensive supportive management, which included osmotic therapy, antiepileptic treatment, mechanical ventilation, and vasopressor support, failed to reverse the neurological decline. Ultimately, the patient developed irreversible loss of brainstem reflexes and deep coma.Conclusion
This case underscores a previously unrecognized and severe pattern of delayed-onset, fatal neurotoxicity associated with blinatumomab, which can occur beyond the conventional early treatment window and despite prior tolerance to the drug. Clinicians must remain vigilant for neurological symptoms linked to fever throughout all treatment phases. Further research is urgently required to elucidate risk factors, identify predictive biomarkers, and refine monitoring strategies to avert catastrophic central nervous system injury in pediatric patients undergoing T-cell-engaging immunotherapy.