Aggressive B-cell lymphoma is a heterogeneous entity with disparate outcomes based on clinical and pathological characteristics. While most tumors in this category are diffuse large B-cell lymphoma (DLBCL), the recognition that some cases have high-grade morphology and frequently harbor MYC and BCL2 and/or BCL6 translocations has led to their separate categorization. These cases are now considered distinct from DLBCL and are named "high-grade B-cell lymphoma" (HGBL). Most are characterized by distinct rearrangements, but others have high-grade morphological features without these and are called HGBL-not otherwise specified. Studies have demonstrated that this group of diseases leads to poor outcomes following standard rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone therapy; retrospective and recent single-arm, multicenter studies suggest they should be approached with dose-intense treatment platforms. As yet, this has not been validated in randomized trial settings due to the rarity of these diseases. In the relapsed and refractory setting, novel approaches such as anti-CD19 chimeric antigen receptor T cells and antibodies against CD19 have demonstrated high efficacy in this subgroup. Recently, genomic studies have made much progress in investigating some of the molecular underpinnings that drive their lymphomagenesis and have paved the way for testing additional novel approaches.
Copyright © 2021 by The American Society of Hematology.