Systemic Immune Alterations in Paediatric Classical Hodgkin Lymphoma With CCL17 and MCP-4 as Diagnostic and Predictive Biomarkers.
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BACKGROUND: Paediatric classical Hodgkin lymphoma (cHL) is the most common malignancy in adolescents, and despite excellent survival, a subset of patients experiences treatment failure or severe long-term toxicity, underscoring the need for improved risk stratification. Early response assessment is particularly important, as it guides decisions on radiotherapy, where overtreatment can lead to substantial late effects. METHODS: In the context of a large-scale systems-level immunomonitoring initiative, we specifically examined paediatric cHL and profiled their systemic immunology alongside children with intra- and extracranial solid tumours and other lymphomas. Through longitudinal sampling before and after treatment, we aimed to identify diagnostic and prognostic biomarkers relating immune profiles to early treatment response and risk of developing neutropenic fever. RESULTS: Plasma CCL17 and MCP-4 were markedly elevated in cHL compared with other paediatric lymphomas and other solid tumours, with distinct immune cell compositions, particularly between cHL and extracranial tumours. CCL17 and MCP-4 negatively correlated with age in extracranial and intracranial tumours but not in cHL, indicating disease-specific regulation. Chemotherapy induced consistent protein changes in cHL and eliminated CCL17 and MCP-4 differences between cHL and other lymphomas. Lower baseline MCP-4 and greater CCL17 reduction after chemotherapy were associated with favourable early response, while lower granzyme levels identified patients at higher neutropenic fever risk. CONCLUSION: Together, these exploratory findings highlight clinically relevant biomarkers in a paediatric oncology context, with the potential to enhance diagnostic precision, guide response-adapted therapy and effectively allocate supportive care, thereby improving outcomes for children with cHL. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.