Investigating Neurofilament Light Chain as a Potential Biomarker of Chemotherapy Induced Peripheral Neuropathy in Children and Adolescents

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Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a common treatment side effect in both pediatric and adolescent young adult patients (AYAs). CIPN causes significant clinical challenges. CIPN detection in children and AYAs remains challenging, with poor sensitivity among providers, particularly in identifying less severe cases. Neurofilament light chain (NfL) is an emerging biomarker that has shown promising correlation in adult oncology studies, with the potential to serve as an early and sensitive biomarker of CIPN. This pilot study aimed to describe changes in NfL in children and AYAs with CIPN. Methods This single-center, prospective study examined patients aged 2-25 years with leukemia or lymphoma who received a chemotherapy regimen which included a tubulin toxin. CIPN was assessed using the FACT-GOG-NTX. Outcomes were evaluated at baseline, during therapy, and 6-12 weeks after last chemotherapy. NfL values were reported as the Normalized Protein eXpression (NPX) per OLINK standard reporting on a log2 scale. Negative NfL values were excluded from percent change calculations. Values were calculated at baseline, first follow-up, and at 90 days or the closest visit to 90 days. Results Data from participants ( n =30) with B-lymphoblastic leukemia ( n =12), Hodgkin lymphoma ( n =14), and mature B-cell lymphoma ( n =4) were analyzed. Of those, 10 participants had NfL analysis, with a median% change in baseline NfL of 57.28%. Mean NfL levels increased from baseline timepoint (mean 2.32, median 2.16) to time point 2 (mean= 3.28, median 3.47) and remained increased at the follow-up visit closest to 90 days (mean 3.85, median 4.38). All participants had CIPN as evidenced by increased FACT-GOG-NTX scores. The majority of scores worsened longitudinally over time correlating with progressively worsening neuropathy. There was a significant correlation between NfL values and FACT-GOG-ntx scores both throughout the study (ρ=-31, p=0.004) and between percent change from baseline value (ρ=-.45, p<0.001), with higher NfL correlating to worse neuropathy. Conclusion We report the first investigation of NfL in the pediatric and AYA cancer setting as a novel biomarker for CIPN detection. Changes in biomarker were detectable early in therapy and correlated with evidence of CIPN. Results from this pilot study will serve as the foundation for future studies to continue investigating NfL as an early and objective detection measure of CIPN in this unique patient population. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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