Lymphomas

Hodgkin’s lymphoma (HL) is a monoclonal lymphoid neoplasm that is mainly characterized by multinucleated Reed–Sternberg cells on a background of non-neoplastic inflammatory cells. The incidence rate of Hodgkin’s lymphoma is 2.5 new cases per 100,000 people per year (1). Paraneoplastic syndromes are conditions that are related to malignancy; however, they are not a result of tumor invasion or compression of malignant tissues. These paraneoplastic syndromes can occur virtually at any point in the disease course, and paraneoplastic syndromes in HL and their various forms are not well studied. In this review article, we will be discussing paraneoplastic syndromes in general and then delve into specific syndromes seen in HL, followed by a brief discourse regarding their early recognition and timely management. Full article

Anti-CD20 monoclonal antibodies (mAbs) have revolutionized the treatment of lymphomas by improving the survival of patients, particularly in conjunction with chemotherapy. Until recently, the gold standard was based on the utilization of Rituximab (RTX) combined with chemotherapy. With our better understanding of monoclonal antibody (mAb) engineering, anti-CD20 mAb therapy has evolved to enhance clinical outcomes by improving pharmacokinetics, safety, activity and immunogenicity. Efforts to improve the on-targeting CD20 expressed on lymphomas through novel bioengineering techniques have led to the development of newer anti-CD20 mAbs that have accentuated complement-dependent cytotoxicity (CDC), antibody-dependent cell medicated cytotoxicity (ADCC), and/or a direct killing effect. There are several anti-CD20 monoclonal antibodies that have been evaluated for the treatment of lymphomas, some of which are now approved in addition to RTX. Full article

Non-Hodgkin lymphomas (NHLs) represent a diverse group of hematologic malignancies derived from various cells. B-cell NHLs represent the largest fraction of lymphomas diagnosed and treated in the United States. Standard chemo-immunotherapies with rituximab and multiagent cytotoxic regimens have proven to be effective in the management of these lymphoproliferative neoplasms; nonetheless, a considerable fraction of patients still experience relapse or have treatment-refractory disease. Therapeutic advances using novel immunotherapeutic agents as well as cell-based treatments, such as chimeric antigen receptor (CAR) T-cell therapies, have improved the outcomes of relapsed/refractory (R/R) B-cell NHL. Most of these new treatment strategies are not curative and most patients succumb to R/R disease, leaving this population with an unmet need for effective and well-tolerated therapeutic options. One of these up-and-coming options are bispecific antibodies (BsAb), either as single agent or in combination with other medications. Conclusion: BsAbs offer a novel “off the shelf” chemotherapy-free approach in the management of R/R B-cell NHL. Advancements in antibody construct design along with improved safety profile and clinical effectiveness of the most recent BsAbs suggest that these agents are a promising new option in the management of R/R B-cell NHL. Full article

The diagnosis and treatment of lymphoid neoplasms have undergone a continuously progressive positive change in the last three decades, with accelerated progress in the previous decade due to the advent of genomics in cancer diagnosis. Significantly, there has been an increasing emphasis on integrating molecular genetics with clinical, morphologic, immunophenotypic, and cytogenetic evaluation for diagnosis. As we think of moving forward with further advances in the genomics era, it is first helpful to understand our current state of knowledge and how we achieved it in the challenging and complex field of lymphoid neoplasms, which comprise very heterogeneous neoplastic diseases in children and adults, including clinically acute lymphoblastic leukemias (ALLs) arising from precursor lymphoid cells and clinically indolent and aggressive lymphomas arising from mature lymphoid cells. This work aims to provide an overview of the historical evolution and the current state of knowledge to anyone interested in the field of lymphoid neoplasms, including students, physicians, and researchers. Therefore, I discuss this complex topic in three review manuscripts, designated Parts 1–3. In Part 1, I explain the basis of the diagnostic classification of lymphoid neoplasms and its evolution up to the current fifth edition of the World Health Organization classification of hematolymphoid neoplasms, and the crucial importance of diagnostic tumor classifications in achieving and advancing patient care and precision medicine. In the second and third manuscripts, I discuss current diagnostic considerations for B-ALL and T-ALL (Part 2) and common indolent and aggressive mature leukemias/lymphomas (Part 3), including significant updates in the WHO 2022 classification, newly described entities, and concepts, including genetic predisposition to ALLs and lymphomas, and throughout emphasizing the essential integration of molecular genetics with clinical, morphologic (pathologic), immunophenotypic, and cytogenetic evaluation, as is required for precise diagnosis of the type of lymphoma/leukemia in any patient. Full article

MYC deregulation, a cardinal event in Burkitt lymphoma (BL) pathogenesis, necessitates the elucidation of the molecular mechanisms governing MYC activation to devise innovative and effective therapeutic strategies. The t(8;14)(q24;q32) chromosomal translocation commonly observed in hematological malignancies results in MYC deregulation, endowing cancer cells with a competitive edge through heightened cell proliferation, cell cycle progression, apoptosis evasion, and metabolic reprogramming. Recent discoveries of recurrent MYC mutations in BL underscore the potential of precision medicine, employing tailored therapeutics to specifically inhibit MYC activity. However, the intricate genetic landscape of BL, featuring additional alterations, such as mutations in TP53, TCF3, and ID3, may necessitate a combinatorial approach targeting multiple oncogenic pathways for effective intervention. Despite significant strides in hematological malignancy treatment, a comprehensive understanding of the molecular mechanisms underpinning MYC’s oncogenic properties remains crucial for the potential development of highly potent and selective MYC-directed cancer therapies. This review offers an in-depth analysis of MYC translocation and its implications in Burkitt lymphoma, with a spotlight on cutting-edge advances in research and emerging therapeutic paradigms. Full article