Biomarkers to reform approaches to therapy-induced neurotoxicity (BRAIN), a substudy in the ALLTogether1 leukemia protocol

New treatments and international collaboration have led to survival rates >90% for pediatric acute lymphoblastic leukemia (ALL), but treatment-related toxicity is a problem. Since 2019 a new treatment protocol, ALLTogether1, aiming to reduce toxicity has been used in Sweden.

Up to 40% of children have neurocognitive sequelae after previous protocols and several therapies in ALLTogether1 can lead to central nervous system (CNS) toxicity. This study aims to evaluate risk factors for CNS toxicity and identify biomarkers for neurocognitive impairment.

We will also compare standard neuropsychological evaluations with a more cost-effective, computer-based method.This study is a substudy of the ALLTogether1 protocol and will be performed in 12 countries. In Sweden ca 240 children will be recruited.

Clinical data in the ALLTogether1 research database will be combined with computer-based cognitive outcome and questionnaires on cognitive processes, lifestyle, and quality of life.

In Sweden, biological samples will be collected before, during, and after treatment and analyzed for protein levels between groups with different outcomes.Identification of subgroups of children with specific neurocognitive impairment after treatment would allow us to implement interventions and support them and their families.

We believe that most survivors of childhood ALL have subtle neurocognitive deficits that affect their quality of life. In these children even small interventions can make a difference.