Analysis of Epstein–Barr Virus and Tumor‐Derived Circulating Plasma DNA in Children and Young Adults With Classical Hodgkin Lymphoma in East Africa

BACKGROUND: Pediatric Hodgkin lymphoma in sub-Saharan Africa is frequently associated with Epstein-Barr virus (EBV), providing a unique opportunity to investigate the molecular characteristics and clinical significance of EBV-associated disease in an understudied population. PROCEDURES: We conducted an observational cohort study of 50 children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) in Tanzania and Uganda. Plasma cell-free DNA collected at diagnosis was analyzed for circulating tumor DNA (ctDNA), EBV-derived biomarkers, and somatic mutations. Associations between clinical, molecular, and survival outcomes were assessed using correlation analyses and Cox proportional hazards models. RESULTS: The median age was 12 years and 62% of participants were male. Most patients presented with advanced-stage disease. ctDNA was detected in 60% of patients with a low mutational burden, while EBV DNA was detected in 92% of cases. Male patients exhibited higher EBV-derived markers and fewer TNFAIP3 and B2M mutations. At a median follow-up of 17.2 months, overall survival was 84% and event-free survival was 50%; male sex and elevated lactate dehydrogenase independently predicted inferior event-free survival. CONCLUSIONS: These findings reveal a low mutational burden and sex-associated molecular and clinical differences in EBV-positive cHL.