title: Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude lifetime cohort study.
abstract: OBJECTIVE
  To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion.
  
  
  RESULTS
  Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment.
  
  
  CONCLUSIONS
  This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.
authors.affiliation: All authors: St Jude Children's Research Hospital, Memphis, TN.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
authors.forename: Tara M
authors.initials: TM
authors.lastname: Brinkman
authors.forename: Chenghong
authors.initials: C
authors.lastname: Li
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Ness
authors.forename: Deo Kumar
authors.initials: DK
authors.lastname: Srivastava
authors.forename: James G
authors.initials: JG
authors.lastname: Gurney
authors.forename: Cara
authors.initials: C
authors.lastname: Kimberg
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009422:Nervous System Diseases / Q000175:diagnosis / Q000503:physiopathology*; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000503:physiopathology* / Q000628:therapy*; D012307:Risk Factors; D017741:Survivors / Q000706:statistics & numerical data; D013997:Time Factors; D055815:Young Adult