Treatment-related Changes in Cerebrospinal Fluid Markers of Oxidative Stress and Neurodegeneration During Therapy for Childhood Acute Lymphoblastic Leukemia.

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) frequently exhibit treatment-related neurocognitive impairment, although there is substantial interpatient variability in this outcome. Analysis of biomarkers that reflect the impact of chemotherapy during the two years of treatment for ALL offers the potential to identify children who have subclinical treatment-related neurotoxicity at a time when a protective intervention could prevent the development of persistent impairment.

Methods: We prospectively measured markers indicative of oxidative stress (8-hydroxydeoxyguanosine; 8OHdG) and neurodegeneration (total tau) in cerebrospinal fluid (CSF) collected at five timepoints before and during the first year of chemotherapy for ALL among 529 patients enrolled on DFCI ALL Consortium protocol 16-001 (NCT03020030).