Analysis of Epstein–Barr Virus and Tumor‐Derived Circulating Plasma DNA in Children and Young Adults With Classical Hodgkin Lymphoma in East Africa
Clara Chamba, Heavenlight Christopher, Emmanuel Josephat, Julius Sseruyange, Alisen Ayitewala, Helene Dreau, Adam Burns, Isaac Otim, Priscus Mapendo, Leah Mnango, Alex Mremi, Edrick Elias, Caroline Achola, William Mawalla, Lulu Chirande, Jacqueline Kamanga, Ismail Legason, Salama Mahawi, Godlove Sandi, Heronima J. Kashaigili, Paul Shadrack Ntemi, Erick Magorosa, Daniel Mbwambo, Martin Ogwang, Dimitrios Vavoulis, Emmanuel Balandya, Anthony Cutts, Eli Mkwizu, Anna SchuhABSTRACT
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.