Neurocognitive outcomes in survivors of ALL: Risk patterns and individual profiles in a single-protocol cohort

Increasing survival probabilities among children and young adults with acute lymphoblastic leukemia (ALL) have led to a growing population at risk for long-term neurocognitive sequelae. This study investigated cognitive functioning among individuals treated for ALL under the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol in Eastern Denmark, including performance across multiple domains and associations with age at diagnosis, sex, time since end of treatment, hematopoietic stem cell transplantation (HSCT), and neurotoxic events during treatment.

Eighty-three survivors of ALL diagnosed before age 25 underwent neurocognitive testing at a median of 7.24 years post-treatment (interquartile range: 4.20-8.78). Performance was measured as age-standardized Z scores derived from normative data. Impairment was defined as Z ≤ -1.3 and severe impairment as Z ≤ -2.0. Multiple linear regression was used to investigate associations between cognitive outcomes and clinical risk factors.

Average performance was generally comparable to norms, but at least 38.6% of participants showed severe impairment in one or more domains, and at least 12% in two or more. Younger age at diagnosis was associated with poorer processing speed, executive functions, and non-verbal reasoning, while HSCT was associated with poorer processing speed and non-verbal reasoning.

Although average performance of the participants was generally comparable to norms, a notable proportion exhibited multi-domain, severe cognitive impairment. Associations with age at diagnosis and HSCT indicate potential for risk-stratified cognitive monitoring and targeted interventions.