Delayed neurotoxicity associated with therapy for children with acute lymphoblastic leukemia.
Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including craniospinal irradiation, nucleoside analogs, corticosteroids, and antifolates. In this review, we describe the characteristic radiographic findings and neurocognitive deficits seen among survivors of childhood ALL. We summarize what is known about the pathophysiology of delayed treatment-related neurotoxicity, with a focus on the toxicity resulting from pharmacologic disruption of folate physiology within the central nervous system. Finally, we suggest testable strategies to ameliorate the symptoms of treatment-related neurotoxicity or decrease its incidence.
Cole
Peter D
PD
Department of Pediatrics and Pharmacology, Robert Wood Johnson Medical School/UMDNJ, The Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, USA. colepd@umdnj.edu
Kamen
Barton A
BA
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000528:radiation effects*; D002648:Child; D016371:Cranial Irradiation / Q000009:adverse effects*; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000209:etiology; D002658:Developmental Disabilities / Q000175:diagnosis / Q000209:etiology*; D005492:Folic Acid / Q000502:physiology; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000209:etiology*; D009483:Neuropsychological Tests; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000209:etiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology*; D012307:Risk Factors
D000970:Antineoplastic Agents; D005492:Folic Acid