Acute Neurotoxicity in Children Treated for Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma: A 10-Year...

Background: Recent advances in childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) management provide higher survival rates at the cost of increased toxicities. Acute neurotoxicity affects up to 10% of patients, requiring rapid recognition and treatment. Methods: A retrospective observational study was performed to determine the frequency, clinical manifestations, radiological characteristics, treatment options and outcome of acute neurological adverse events in pediatric patients with lymphoid malignancies at the Department of Oncology and Hematology, Children's Hospital Zagreb, Croatia. Results: A total of 56 patients (48 ALL and 8 LL, male/female ratio 1:1, average age 5.4 years) were treated mainly according to the ALL-IC BFM 2009 protocol. The B-immunophenotype was the most frequent (85.7%). Most patients were stratified to the intermediate risk group (39.3%), and two were initially diagnosed with central nervous system infiltration. Acute neurotoxic events were registered in 11 patients (19.6%), most commonly in the 6-10-year age group (66.7%), predominately in females (72.7%) and high-risk group (54.5%). The most frequent clinical presentation was seizures (83.3%), with status epilepticus in four cases. We detected electroencephalogram (EEG) irregularities in almost all patients and various morphological changes in the brain magnetic resonance imaging (MRI), most often consistent with posterior reversible encephalopathy syndrome and leukoencephalopathy. Approximately half the patients received prolonged antiepileptic therapy. No apparent residual neurologic manifestations have been observed. Conclusions: Acute neurotoxicity is a rather frequent treatment-related adverse event, associated with high-risk disease. Early recognition and timely management are essential for rapid recovery and optimal outcomes.