LAUSR

Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1 464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies (GWAS), and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1 166 patients. Findings were validated in an Australian independent cohort of children with ALL (n=797) where two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1 464 (9.2%) patients experienced CNS toxicity with cumulative incidence of 8.7% (95% CI: 7.31-10.20) at 12 months from diagnosis. Patients aged ≥10 years had higher risk of CNS toxicity than younger patients (16.3% vs 7.4%; p.