Cell cycle characteristics and Epstein–Barr virus are differentially associated with aggressive and non-aggressive subsets of Hodgkin lymphoma in pediatric patients

We investigated the correlation of tumor characteristics with clinico-biological markers of aggressive disease, evaluated by Ann Arbor stage, risk group, B-symptoms, number of involved anatomic areas, mediastinal mass, nodular sclerosis (NS) grade, and risk, in pediatric Hodgkin lymphoma (HL). Leukopenia and extranodal disease influenced event-free survival (p = 0.032 and p = 0.041). In multivariate analysis, extranodal disease was associated with high number of tumor-infiltrating eosinophils (p = 0.035) and Ki67 < 50% (p = 0.024); B-symptoms with Ki67 > or =75% (p = 0.027) and high LDH levels (p = 0.001); and mediastinal mass with leukopenia (p = 0.048), NS grade II (p = 0.025), and high-risk (p = 0.046). Furthermore, low stages correlated with Ki67 > or =50% (p = 0.005) and Epstein-Barr virus (EBV) (p = 0.065). Low-risk NS was associated with EBV (p = 0.014). Hierarchical cluster analysis identified two clusters, one composed of high-risk patients and cell cycle and apoptosis features, and the other including low-risk patients, EBV, and low-risk NS. Our results show the association of biological markers with disease aggressiveness in pediatric HL.