Primary Mediastinal B-Cell Lymphoma in Children and Young Adults

Primary mediastinal B-cell lymphoma (PMBCL) is a rare but aggres-sive mature B-cell lymphoma that arises from thymic B cells and most commonly affects adolescents and young adults. PMBCL is now rec-ognized by the WHO as a distinct entity from diffuse large B-cell lymphoma (DLBCL), not otherwise specified, with a unique clinical presentation and distinct morphologic features and molecular altera-tions. Similar to classic Hodgkin lymphoma, PMBCL tumors are charac-terized by alterations in the nuclear factor -KB and JAK/STAT pathways. These tumors also exhibit an immune evasion phenotype marked by upregulation of PD-L1 and loss of B2M. Historic data indicates that out-comes for pediatric patients with PMBCL are inferior compared with pediatric patients with DLBCL treated on the same protocols, and there is no current standard approach to initial treatment. Common regimens used for children with PMBCL include multiagent chemotherapy regi-mens designed for Burkitt lymphoma, such as Lymphomes Malins B (LMB)-based or Berlin-Frankfurt-Mueuronster (BFM)-based chemotherapy 6 rituximab. Based on initial data in adults showing excellent outcomes with the use of DA-EPOCH-R regimens, these regimens have also been adopted in pediatrics, although with mixed results. Novel agents are currently being studied in PMBCL with the goal of improving outcomes and reducing reliance on radiation and/or high-dose chemotherapy. Im-mune checkpoint blockade with PD-1 inhibition is of particular interest given the upregulation of PD-L1 in PMBCL and the known efficacy of these agents in the relapsed setting. Future efforts in PMBCL will also seek to determine the role of FDG-PET in evaluating response to ther-apy and the role of biomarkers in risk stratification.