Neurocognitive outcomes among children who experienced seizures during treatment for acute lymphoblastic leukemia

• Published in: Pediatric blood & cancer Vol. 64; no. 8
• Main Authors: Nassar, Stephanie L., Conklin, Heather M., Zhou, Yinmei, Ashford, Jason M., Reddick, Wilburn E., Glass, John O., Laningham, Fred H., Jeha, Sima, Cheng, Cheng, Pui, Ching‐Hon
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2017
• Subjects: Acute lymphoblastic leukemia; Adolescent; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Attention; Change detection; Chemotherapy; Child; Child, Preschool; Children; Cognition; Cognition Disorders - epidemiology; Cognition Disorders - etiology; Cognitive ability; cognitive late effects; Cytarabine - administration & dosage; Cytarabine - adverse effects; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Female; Group dynamics; Hematology; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - adverse effects; Incidence; Information processing; Leukemia; Leukoencephalopathies - epidemiology; Leukoencephalopathies - etiology; Leukoencephalopathy; Lymphatic leukemia; Magnetic Resonance Imaging; Male; Mercaptopurine - administration & dosage; Mercaptopurine - adverse effects; Methotrexate - administration & dosage; Methotrexate - adverse effects; Neuropsychological Tests; Neurotoxicity; NMR; Nuclear magnetic resonance; Oncology; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Risk Factors; Seizing; seizure; Seizures; Seizures - chemically induced; Seizures - complications; Short term memory; Vincristine - administration & dosage; Vincristine - adverse effects; working memory; leukoencephalopathy; leukemia; seizure; cognitive late effects; working memory
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.26436

Background Limited information is available regarding neurocognitive outcomes of children who experience seizures during treatment for acute lymphoblastic leukemia (ALL). Accordingly, the main objectives of this study were to determine the incidence and risk factors for treatment‐related seizures among children with ALL, and the neurocognitive outcomes associated with treatment‐related seizures. Procedure Prospective neuropsychological assessment and magnetic resonance imaging (MRI) were planned for all 498 patients with newly diagnosed ALL enrolled on the St. Jude Total Therapy XV (TOTXV) protocol at three time points. The study database was reviewed retrospectively to identify those with treatment‐related seizure. To assess neurocognitive changes associated with seizure, each patient with treatment‐related seizure was matched with two cohort patients without seizure for age at treatment, gender, race, and treatment intensity. Results Nineteen patients developed seizure, with a 2‐year cumulative risk of 3.82 ± 0.86% (SE). No risk factors were identified to be associated with the development of seizure, with a possible exception of intensive chemotherapy used on the standard/high‐risk arm as compared to the low‐risk arm. Neuropsychological performance of the seizure group, as compared to normative scores and nonseizure control cohort, indicated problems in attention, working memory, and processing speed. Cognitive deficits persisted 2 years after therapy, with additional declines in intellectual function observed. MRI indicated early neurotoxicity among the seizure group, as evidenced by greater leukoencephalopathy on initial examinations. Conclusion Treatment‐related seizures were associated with leukoencephalopathy and decreased neuropsychological performance. Prospective studies are needed to detect changes in neurocognitive status associated with long‐term functional impairment.