title: Long-term neurocognitive outcomes in young adult survivors of childhood acute lymphoblastic leukemia.
abstract: Five-year survival rates of childhood acute lymphoblastic leukemia (ALL) exceed 80% due to central nervous system-directed treatment including cranial radiation (CRT) and chemotherapy. However, these treatments are associated with neurocognitive compromise, the extent of which is correlated with higher dose and younger age at treatment. The aims of this study were to explore long-term neurocognitive outcomes in adult survivors of childhood ALL, and to identify measures sensitive to neurotoxicity in long-term survivors. We examined 24 adults who received 18 Gy CRT and chemotherapy for treatment of ALL between ages 2 and 15 years (median, 5.5). Time since diagnosis ranged from 6 to 26 years (median, 16.6). Younger age at diagnosis and longer time since diagnosis were associated with lower scores on a computerized battery that requires speed and accuracy across a number of domains (MicroCog), and other standardized neurocognitive tests. When compared with population norms, MicroCog indices were below average in survivors diagnosed with ALL before age 5, but only the reasoning/calculation index was below average in survivors diagnosed with ALL after age 5. In contrast, intelligence quotient (IQ) scores were average. In addition to confirming earlier studies showing that younger children are more vulnerable to treatment-related neurotoxicity, here we show that deficits exist many years post treatment even with a relatively lower dose of CRT, and that these deficits are especially evident on tasks involving rapid processing of information.
authors.affiliation: Psychosocial Oncology & Palliative Care, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. kim.edelstein@uhn.on.ca
authors.forename: Kim
authors.initials: K
authors.lastname: Edelstein
authors.forename: Norma
authors.initials: N
authors.lastname: D'agostino
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Bernstein
authors.forename: Paul C
authors.initials: PC
authors.lastname: Nathan
authors.forename: Mark L
authors.initials: ML
authors.lastname: Greenberg
authors.forename: David C
authors.initials: DC
authors.lastname: Hodgson
authors.forename: Barbara Ann
authors.initials: BA
authors.lastname: Millar
authors.forename: Normand
authors.initials: N
authors.lastname: Laperriere
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Spiegler
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000209:etiology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology* / Q000401:mortality; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007223:Infant; D007360:Intelligence; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000628:therapy*; D015996:Survival Rate; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult