Cognitive, behaviour, and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study

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.

Findings: 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.

Interpretation: 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.

Funding: National Cancer Institute, American Lebanese-Syrian Associated Charities.