Search Results (20)

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

Radiation therapy is a key contributor to positive outcomes in hematological malignancies. However, this is contingent on minimizing the exposure of critical normal organs. The introduction of computed tomography (CT) for radiation treatment planning and the development of sophisticated dose calculation algorithms has transformed the radiation therapy field and made it possible to transition from conventional involved-field radiation to modern involved-site radiation therapy. Thanks to rapid advances in drug discovery, treatment strategies for many hematological malignancies have evolved to incorporate targeted and cellular therapies, in some cases even allowing the replacement of chemotherapy. As a result, new opportunities have been created for radiation to address relapses after more lines of therapy, identify disease-involving sanctuary sites, and bridge to the subsequent therapy. When considering radiation in patients receiving novel therapies, who may also be more heavily pretreated, respecting the critical and normal structures at all costs is imperative. In this document, we will describe modern techniques used to deliver state-of-the-art radiation therapy and practical considerations to ensure the accurate treatment of the target while avoiding normal organs at risk. Full article

Radiotherapy and/or chemotherapy have been used for nearly 100 years to treat lymphoma. Recently, immunotherapy has been incorporated into the treatment of lymphomas. Here, we will review both the role of immunotherapy in lymphoma as well as the feasibility of incorporating immunotherapies with conventional lymphoma treatments, especially radiotherapy. Immunotherapy agents include checkpoint inhibitors that target the PD-1/PD-L1 axis, CTLA-4, or CD47. In addition, other immunotherapy agents such as bi-specific antibodies and CD19 CAR-T cell therapy are being implemented in various non-Hodgkin’s lymphomas. Extrapolating from observations in other disease sites and incorporating immunotherapy with conventional treatments of lymphoma, including radiotherapy, may have opposing effects. Radiotherapy may stimulate anti-tumor immune responses that synergize with immunotherapies. In contrast, radiotherapy, as well as chemotherapy, may also induce local and systemic immune dysfunction which reduces the efficacy of immunotherapies. With newer radiation treatment techniques and limited radiation fields, it is likely that the efficacy of immunotherapy can be maintained when included with conventional treatments. Therefore, there remains an unmet need to better understand the role of immunotherapy alone and in combination with current treatments in lymphoma patients. Full article

Radiation therapy has been proven to be highly effective in the treatment of lymphoma. With increasing rates of long-term survival, the reduction in toxicity has gained importance. The evolving understanding of the diseases’ biology, as well as technical and conceptual advances, allows for a precise and individualized application of irradiation. Smaller treatment fields and safety margins make it possible to spare healthy neighbouring tissue (organs at risk). The International Lymphoma Radiation Oncology Group (ILROG) has developed several guidelines to optimize radiotherapy treatment in lymphoma patients. Since its introduction in 2013, involved site radiotherapy (ISRT) has been adopted as the standard of care in most treatment regimens in adult lymphoma. This article serves as a summary of the current ILROG guidelines, also considering contemporary developments and possible future directions. Full article

Lymphedema is an under-recognized and underappreciated disease. Advances in imaging and a deeper understanding of the pathophysiology of lymphedema are shedding new light on this disease that affects millions of people worldwide. As new evidence continues to emerge about the microcirculation and revised Starling Principle, etiological factors, related conditions, specific genes, and surgical innovations, the traditional approach to management must also evolve. This evolution is vital to maximize outcomes and improve quality of life. This commentary is a call to action to embrace innovation to better manage lymphedema and expand educational opportunities by leveraging technology to properly train healthcare providers to manage this disease. 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

Under inflammatory conditions including lymphatic disorders, bone marrow-derived myeloid cells often express lymphatic endothelial cell (LEC) markers, and these cells are then called LEC progenitor cells, which extend lymphatic vessels by fusing with existing lymphatic vessels. However, studies on the mechanism of lymphatic regeneration using three-dimensional images of lymphatic structures are limited. In this study, scanning electron microscopy (SEM) was used to observe the three-dimensional structure of lymphangiogenesis in a mouse model of secondary lymphedema. The model was established in C57BL/6J mice via circumferential incision in the inguinal region of the left hind limb. Skin samples were obtained from the lymphedema region on days 2, 5, and 8 after surgery. To determine lymphatic vessel positions using SEM analysis, we detected anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity in serial sections and overlaid them during SEM observation. On days 2 and 5, spherical cells, probably myeloid cells, were attached and fused to the LYVE-1-positive lymphatic vessel walls. On day 8, spherical cells were converted to string-shaped cells, forming a new lymphatic vessel wall resembling an intraluminal pillar. Our results showed the newly formed lymphatic vessel wall extended into the lumen, suggesting intussusceptive lymphangiogenesis. Full article

Lymphedema is a chronic and debilitating disease that affects up to 250 million patients worldwide. Recent advances in understanding its pathophysiology, along with improved diagnosis and microsurgical techniques, have enhanced our ability to cope with the challenging task of treating this disease. This review provides an overview of the disease from a surgeon’s point of view, including existing imaging modalities used for preoperative assessment, as well as surgical procedures used in its treatment. The advantages and drawbacks of various existing modalities used for the pre- or intraoperative assessment of lymphatic vessels are discussed. Lymphedema treatment has shifted from palliative debulking procedures (liposuction and direct excision) to those aimed at restoring lymphatic flow and countering the pathophysiology of the disease (lymphaticovenous anastomosis and vascularized lymph node transfer). A combination of both approaches can result in a synergistic benefit for patients and is discussed in this review. Despite recent advances, some controversies persist, and further studies are needed to better define surgical treatment algorithms. 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

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, morphological, immunophenotypic, and cytogenetic evaluation for diagnosis. As we think of moving forward with further advances in the genomics era, it will be 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 have discussed 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 emphasizing throughout the essential integration of molecular genetics with clinical, morphologic, immunophenotypic, and cytogenetic evaluation, as required for the 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

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing regeneration with degeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardio-renal system, the new pillar of heart failure and kidney disease—Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study. Full article

Lymph node (LN) metastasis is recognized to be an important prognostic factor for esophageal cancer (EC). However, there is no worldwide uniform classification system, and no consensus exists on the extent of the lymphadenectomy. Recently, an international observational cohort study was conducted to evaluate the distribution of LN metastasis in EC patients. Moreover, this could be a milestone to establish a standard classification system and provide new insights to determine the extent of LNs that should be target for treatment. With regard to surgical procedures, three-field lymphadenectomy seems to be promising to improve the prognosis with EC patients. However, extended lymphadenectomy could lead to postoperative complications. The development of minimally invasive esophagectomy (MIE) has allowed us to retrieve cervical paraesophageal nodes without cervical incision and reduce the incidence of postoperative complications. Therefore, it may be possible that the era of MIE could propose the modern extent of LN dissection in the future. Additionally, one of the key components in lymphadenectomy for EC was thoracic duct and surrounding tissues. Although there is some evidence of LN metastasis surrounding the TD, the survival benefit of TD resection is still debatable. With regard to esophagogastiric junction cancer, the extent of LN dissection could be determined by the length of esophageal involvement. We believe further understanding of LN metastasis of EC patients will contribute to establish a global standard of treatment and improve their prognosis. Full article

The diagnosis and treatment of lymphoid neoplasms have undergone a progressively 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 consider 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 have discussed 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 (WHO) 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

Bleomycin-induced pulmonary toxicity (BPT) is a serious and potentially fatal complication of bleomycin, a key component of Hodgkin lymphoma (HL) treatment. Before ours, only one published study evaluated the predictability of 18F-FDG-PET/CT for the early diagnosis of BPT. In this retrospective cohort study, 18F-FDG-PET/CT scans of adult HL patients treated with bleomycin at an urban academic center over five years were assessed by radiologists blinded to the clinical information, and scans were correlated with clinical BPT. We found 11 HL patients with 54 interim or end-of-treatment 18F-FDG-PET/CT scans who had received bleomycin. Five of the eleven (5/11, 45%) patients had radiographic changes in PET/CT and developed clinical BPT. Patients with clinical BPT had higher FDG uptake in lungs compared to those who did not (SUV_max mean 2.66 (CI 1.8–3.7) vs. 0.86 (CI 0.4–1.9), Mann–Whitney U test, p < 0.05). In a separate cohort analysis, we compared HL patients with clinical BPT (9/25, 36%) and without clinical BPT (16/25, 64%) to assess potential risk factors. Low hemoglobin (p = 0.037) and high ESR values (p = 0.0289) were associated with clinical BPT. Furthermore, gender, stage, histology, prior lung radiation, G-CSF, or steroids did not significantly confer a higher risk of BPT. 18F-FDG-PET/CT imaging, which is routinely used to assess treatment response in HL, is useful for early detection of BPT, which can have high mortality and morbidity. Full article