title: Cognitive, behaviour, and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study.
abstract: BACKGROUND
  Survivors of childhood acute lymphoblastic leukaemia (ALL) are at risk for neurocognitive deficits that affect development in adolescence and young adulthood, and influence educational attainment and future independence. We examined a large and diverse cohort of survivors to identify risk predictors and modifiers of these outcomes.
  
  
  METHODS
  In this cohort study, cognitive and behaviour symptoms were assessed via a standardised parent questionnaire for 1560 adolescent survivors of ALL diagnosed between 1970 and 1999. Clinically significant symptoms (≥90th percentile) and learning problems were compared between survivors and a sibling cohort. Multivariable regression models were used to examine associations with demographic and treatment characteristics. Models were adjusted for inverse probability of sampling weights to reflect undersampling of ALL survivors in the expansion cohort. In a subset of survivors with longitudinal data (n=925), we examined associations between adolescent symptoms or problems and adult educational attainment.
  
  
  RESULTS
  Compared with siblings, survivors treated with chemotherapy only were more likely to demonstrate headstrong behaviour (155 [19%] of 752 survivors vs 88 [14%] of 610 siblings, p=0·010), inattention-hyperactivity (15 [19%] vs 86 [14%], p<0·0001), social withdrawal (142 [18%] vs 75 [12%], p=0·002), and had higher rates of learning problems (191 [28%] vs 76 [14%], p<0·0001). In multivariable models among survivors, increased cumulative dose of intravenous methotrexate (ie, >4·3 g/m2) conferred increased risk of inattention-hyperactivity (relative risk [RR] 1·53, 95% CI 1·13-2·08). Adolescent survivors with cognitive or behaviour problems and those with learning problems were less likely to graduate from college as young adults than adolescent survivors without cognitive or behaviour problems.
  
  
  CONCLUSIONS
  Although modern therapy for childhood ALL has eliminated the use of cranial radiation therapy, adolescent survivors treated with chemotherapy only remain at increased risk for cognitive, behaviour, and academic problems that adversely affect adult education outcomes.
  
  
  BACKGROUND
  National Cancer Institute, American Lebanese-Syrian Associated Charities.
authors.affiliation: Department of Psychology, St Jude Children's Research Hospital, Memphis TN, USA. Electronic address: lisa.jacola@stjude.org.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Jacola
authors.affiliation: Pencer Brain Tumor Centre, Princess Margaret Cancer Center, Toronto, ON, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Edelstein
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis TN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, Memphis TN, USA.
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.affiliation: Department of Oncology, Washington University at St Louis, St Louis, MO, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Yale Section of Pediatric Hematology-Oncology and Yale Cancer Center, New Haven, CT, USA.
authors.forename: Nina S
authors.initials: NS
authors.lastname: Kadan-Lottick
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis TN, USA.
authors.forename: Deokumar
authors.initials: D
authors.lastname: Srivastava
authors.affiliation: Department of Oncology, University of Chicago, Chicago, IL, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Henderson
authors.affiliation: Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.affiliation: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis TN, USA.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis TN, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.affiliation: Department of Psychology, St Jude Children's Research Hospital, Memphis TN, USA; Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis TN, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
mesh_terms: D000293:Adolescent; D001519:Behavior; D003071:Cognition; D015331:Cohort Studies; D004522:Educational Status; D005260:Female; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D035781:Siblings / Q000523:psychology; D011795:Surveys and Questionnaires; D017741:Survivors / Q000523:psychology* / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult