LAUSR

Over the last 40 years, we and others have reported that the prognosis of children with advanced mature B-cell lymphoma (Burkitt lymphoma [BL] and diffuse large B-cell lymphoma [DLBCL]) has significantly improved, with the 2-year event-free survival (EFS) increasing from approximately 45– 90% (Fig 1) through the use of short but intense multiagent chemotherapy including fractionated cyclophosphamide, high dose methotrexate, vincristine, prednisone, doxorubicin, cytosine arabinoside, etoposide and, in patients with or at risk of central nervous system (CNS) involvement, the aggressive use of single or triple intrathecal therapy (Cairo et al, 2002, 2007, 2012; Patte et al, 2007). This incredible success has also resulted in significant shortand long-term morbidities and late effects, respectively (Cairo et al, 2002, 2007, 2012; Oeffinger et al, 2006; Patte et al, 2007; Bluhm et al, 2008; Bhakta et al, 2017; Ehrhardt et al, 2018a,2018b). Additionally, the overall survival (OS) is dismal (≤30%), in children who are refractory, progress or relapse off modern French-American-British/Lymphome Malins B (FAB/LMB) type multiagent chemotherapy secondary to chemotherapyresistant disease (Cairo & Pinkerton, 2016; Cairo et al, 2018; Cairo & Beishuizen, 2019). Our group previously demonstrated a ≥98% expression of CD20 in children and adolescents with mature B-cell lymphoma treated on the FAB/LMB 96 trial (Perkins et al, 2003). CD20 is an excellent therapeutic target that is important in normal B-cell signalling and is rarely shed or internalized (Barth et al, 2012). Rituximab, a type I anti-CD20 monoclonal antibody, has been successfully demonstrated to significantly induce B-cell apoptosis and facilitate antibodydependent cellular cytotoxicity and complement-dependent cytotoxicity, and has been demonstrated to be safe to combine with several chemotherapy backbones and significantly increase long term EFS in adults with DLBCL and BL (Coiffier et al, 2002, 2010; Pfreundschuh et al, 2006; Dunleavy et al, 2013). We have further demonstrated the safety and efficacy of dose-dense administration of rituximab in combination with FAB/LMB 96 B4 and C1 backbones in intermediate and high-risk newly diagnosed mature B-cell Fig 1. Comparison of event-free survival by study among disseminated mature B-cell nonHodgkin lymphoma patients from CCG/COG studies (551, 503, 552, 5911, CCG-5961, ANHL01P1). Reproduced with permission from: Cairo, M.S. & Beishuizen, A. (2019) Childhood, adolescent and young adult nonHodgkin lymphoma: current perspectives. British Journal of Haematology. 6 Feb 2019. https://doi.org/10.1111/bjh.15764. Copyright 2019. John Wiley & Sons. COG, Children’s Oncology Group; CCG, Children’s Cancer Group; DLBCL, diffuse large B-cell lymphoma.