Search Results (36)

Background: Lymphomas account for approximately 10% of cancers diagnosed during pregnancy, with Hodgkin’s lymphoma being the most common. However, non-Hodgkin lymphomas, including primary mediastinal large B-cell lymphoma (PMBCL), also represent a significant proportion. Both mediastinal lymphomas and pregnancy develop a hypercoagulable state, increasing the risk of venous thromboembolism and massive pulmonary embolism (PE), requiring extracorporeal membrane oxygenation (ECMO). Methods: Clinical data, blood test and imagings have been collected by the medical records of the patient. Results: We present a 25-year-old woman, at 32 weeks of gestation, who presented to the emergency department with progressive dyspnea and asthenia. Echocardiography revealed a hemodynamically significant pericardial effusion and severe right ventricular dysfunction. Given the severity of her condition, she underwent an emergency caesarean section and subsequently a pericardial drainage. A chest computed tomography scan revealed an incidental mediastinal mass along with a massive PE. Despite pericardial drainage, she remained hemodynamically unstable. Since thrombolysis was contraindicated for the recent cesarean section, venoarterial ECMO was initiated. Systemic anticoagulation was guaranteed by heparin, which shifted to argatroban for heparin resistance. The mediastinal mass was also biopsied, and the diagnosis of PMBCL carried out. Cytoreductive chemotherapy was initiated with the COMP-R regimen (i.e., cyclophosphamide, vincristine, methotrexate, prednisone, and rituximab), and the patient progressively improved up to ICU and hospital discharge. Conclusions: This case highlights the challenges in managing a complicated patient requiring early multidisciplinary intervention, which was crucial for stabilizing the patient and optimizing fetal and maternal prognosis. Full article

Background/Objectives: Primary cutaneous B-cell lymphomas (PCBCL) are a rare and heterogeneous group of non-Hodgkin lymphomas that are confined to the skin at diagnosis and exhibit a tendency for cutaneous recurrence. The 5th edition of the World Health Organization and the 2022 International Consensus Classification recognize three main subtypes: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma/lymphoproliferative disorder (PCMZL/LPD), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT). These subtypes differ in clinical behavior, histopathologic features, immunophenotype, and molecular alterations. Diagnosis and management remain challenging for clinicians. This review aims to provide a comprehensive overview of the defining features and current treatment strategies for PCBCL. Methods: This narrative review synthesizes current literature on the clinical, morphologic, immunohistochemical, and molecular characteristics of PCBCL. It also evaluates the diagnostic utility of immunohistochemistry, gene expression profiling, and molecular assays, particularly in distinguishing primary cutaneous disease from secondary cutaneous involvement by systemic lymphomas. Results: PCFCL arises from germinal center B-cells and must be differentiated from nodal follicular lymphoma. PCMZL/LPD is derived from post-germinal center B-cells and is often linked to chronic antigenic stimulation. Both PCFCL and PCMZL/LPD are indolent and associated with favorable outcomes. By contrast, PCDLBCL,LT is an aggressive lymphoma characterized by genetic alterations activating the NF-κB pathway, commonly including mutations to MYD88 and CD79B. Treatment strategies vary by subtype, ranging from localized therapies for indolent lymphomas to systemic chemoimmunotherapy for aggressive PCBCL. Emerging therapies, such as Bruton tyrosine kinase inhibitors and immunoregulatory agents, are being investigated for relapsed/refractory disease. Conclusions: PCBCL encompass distinct clinicopathologic entities with subtype-specific diagnostic and therapeutic considerations. While current management is guided by clinical behavior, significant knowledge gaps remain regarding the molecular mechanisms underlying skin tropism, immune evasion, and disease progression. Future research could focus on improving molecular characterization and developing personalized and immune-based therapies to enhance outcomes. This review consolidates current knowledge and highlights innovations aimed at advancing the diagnosis and treatment of PCBCL in clinical practice. Full article

Background/Objectives: Myeloid neoplasms are the most common secondary blood cancer in B-cell non-Hodgkin lymphoma (BNHL) patients treated with cytotoxic therapies. We aimed to characterize the genetic and clinicopathologic features of myeloid neoplasms arising after B-cell non-Hodgkin lymphoma (MN-BNHL) by comparing their features with myeloid neoplasms developing after solid cancer (MN-SC). Methods: We retrospectively analyzed the clinicopathologic and genetic data of myeloid neoplasm patients diagnosed between 2008 and 2023, categorized as MN-BNHL or MN-SC. Further NGS analysis was performed on available bone marrow samples with missing genetic data. The genetic profiles of myeloid neoplasms between BNHL and solid cancer groups were compared. Results: Sixteen patients developed MN-BNHL. Among the 11 MN-BNHL patients undergoing NGS, all harbored tier 1 mutations. PPM1D mutations (PPM1Dms) were most frequent (73%), followed by DNMT3A (46%) and TP53 (36%). PPM1Dms were significantly more prevalent than in MN-SC (n = 21), where TP53 mutations were most common (64%) (p < 0.001). PPM1Dms often co-occurred with DNMT3A. They were associated with prior radioimmunotherapy (relative risk (RR): 3.3 and RR 3.57). MN-BNHL patients with PPM1Dms exhibited improved survival compared to those without (p = 0.0376), but this benefit was negated by the presence of TP53 mutations (p = 0.0049). Conclusions: PPM1Dms are a prominent genetic feature in MN-BNHL, suggesting a distinct role in its development compared to MN-SC. Further investigation is needed to elucidate the precise contribution of PPM1D and its interaction with other mutations in BNHL-related myeloid neoplasm development and prognosis. Full article

Epstein–Barr virus (EBV) is one of the most prevalent human viruses worldwide. The COVID-19 pandemic, with its social distancing measures, has disrupted the circulation of many viruses. Delayed EBV primary infection is known to increase the risk of secondary conditions, including infectious mononucleosis, multiple sclerosis, and Hodgkin’s lymphoma. In this context, we aimed to investigate whether EBV seroprevalence has been affected over time, particularly in relation to the COVID-19 period, by analyzing all patients admitted to Amiens University Hospital from January 2013 to December 2023 who underwent EBV serology. During this period, 19,771 EBV serologies were performed and analyzed. The total seropositive rate of EBV infections approached 90%, considering all non-negative serological profiles, with the rate stabilizing after 2017. The number of EBV serologies increased significantly until 2016, as well as the age of the screened patients. Less than 3% of patients remain seronegative after 25 years, indicating a seroprevalence of around 97%. The overall primary infection rate was 2.6%. There was no significant difference in the number of primary infections in 2020–2021, the years associated with confinements and curfews in France in the context of the COVID-19 pandemic, compared with the other years. The overall EBV seroprevalence and age of primary infection remained stable during the study period, suggesting a moderate impact of the COVID-19 pandemic on seroprevalence in this cohort. Full article

Neurolymphomatosis (NL) is a rare manifestation of hematologic malignancies, characterized by a neoplastic infiltration of the peripheral nervous system and cranial nerves (CNs). Non-Hodgkin lymphomas (NHLs) account for 90% of NL cases, while acute leukemia represents 10% of the cases. NL can occur as the first manifestation of a malignancy (primary), or as a relapse or progression of a previously treated disease (secondary). Herein, we report a unique case of NL involving the left orbit and CNs in a 74-year-old female with primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL). Our patient developed secondary neurolymphomatosis involving the left orbit and CNs II, III, V, and VI, supported by clinical, radiologic, and histologic findings. The lacrimal gland enhancement was histopathologically proven to be caused by the direct spread of CNS DLBCL to the lacrimal nerve, a branch of CN V, identifying NL as one of the conditions that can affect this organ. The lacrimal gland could be considered as a more accessible biopsy site when the involvement of CN V is suspected. Full article

Background: The aim of this study was to evaluate real-world clinical outcomes and transplant-related complications of allogeneic stem cell transplantation (alloSCT) for Hodgkin lymphoma (HL). Methods: This was a single-centre, retrospective analysis of relapsed and refractory (R/R) HL patients who received an alloSCT between 1 January 2016 and 29 February 2024 in Hamilton, Ontario. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease/relapse-free survival (GRFS). Results: Twenty-one patients were identified, with thirteen (62%) pre-treated with programmed death 1 (PD-1) blockade with either nivolumab or pembrolizumab. Seventeen (81%) patients underwent related haploidentical donor transplants, while four (19%) patients received a matched unrelated donor transplant. The 2-year OS and PFS rates were 79% (95% CI: 53–92%) and 63% (95% CI: 37–81%), respectively. Trends towards improved OS, PFS, NRM, and GRFS in PD-1-inhibitor-exposed patients were observed. All PD-1-inhibitor-exposed patients who were in complete remission proceeding to alloSCT remained alive at the last follow-up visit. Among the nine patients in partial remission at the time of alloSCT, three deaths were reported, with a 2-year OS of 61%. Conclusions: Our outcome data of a single-centre, heavily pre-treated cohort of Canadian patients confirm that alloSCT with post-transplant cyclophosphamide-based immunosuppression, which has been associated with improvements in PFS, remains a safe and feasible treatment option for patients with R/R HL in the era of checkpoint inhibitor use. Full article

Background/Objectives: Incomptine A (IA) has cytotoxic activity in non-Hodgkin lymphoma (NHL) cancer cell lines. Its effects on U-937 cells include induction of apoptosis, production of reactive oxygen species, and inhibition of glycolytic enzymes. We examined the altered protein levels present in the lymph nodes of an in vivo mouse model. Methods: We induced an in vivo model with Balb/c mice with U-937 cells and treated it with IA or methotrexate, as well as healthy mice. We determined expressed proteins by TMT based on the LC-MS/MS method (Data are available via ProteomeXchange with identifier PXD060392) and a molecular docking study targeting 15 deregulated proteins. We developed analyses through the KEGG, Reactome, and Gene Ontology databases. Results: A total of 2717 proteins from the axillary and inguinal lymph nodes were analyzed and compared with healthy mice. Of 412 differentially expressed proteins, 132 were overexpressed (FC ≥ 1.5) and 117 were underexpressed (FC ≤ 0.67). This altered expression was associated with 20 significantly enriched processes, including chromatin remodeling, transcription, translation, metabolic and energetic processes, oxidative phosphorylation, glycolysis/gluconeogenesis, cell proliferation, cytoskeletal organization, and with cell death with necroptosis. Conclusions: We confirmed the previously observed dose-dependent effect of IA as a secondary metabolite with important potential as an anticancer agent for the treatment of NHL, showing that the type of drug or the anatomical location influences the response to treatment. The IA promises to be a likely safer and more effective treatment to improve outcomes, reduce toxicities, and improve survival in patients with NHL, initially targeting histones and transcription factors that will affect cell death proteins. Full article

Anti-CD19 chimeric antigen receptor (CAR) T-cell and anti-CD20 bispecific antibody therapies (BsAbs) are rapidly moving to earlier treatment lines for patients with B-cell non-Hodgkin lymphoma (B-NHL). The rapid pace of the advancement of these T-cell-engaging therapies is juxtaposed by a lack of a comprehensive understanding of the scope and kinetics of immunodeficiency following these treatments. We review emerging studies detailing the safety and efficacy of CD19 CAR-T and CD20 BsAbs in earlier lines for B-NHL, as well as a discussion of the limited knowledge of immune recovery following these treatments. We integrate the limited consensus prevention and management recommendations, advocating that the management of secondary immunodeficiency following these transformative therapies is an urgent unmet need in immune oncology research. A collaboration between hematologists/oncologists and immunologists in the management of these patients is critical to optimize patient care. Full article

According to the World Health Organization (WHO), the incidence of HCV remains high (around 1.5 million new patients every year), and 80% of patients with acute infection will progress to chronic hepatitis and develop cirrhosis and even liver cancer. Furthermore, some extrahepatic pathologies may be correlated with HCV (such as mixed cryoglobulinemia, porphyria cutanea tarda, lichen planus, glomerulonephritis, Sjogren’s syndrome, Hodgkin and non-Hodgkin cell lymphoma, and others). In view of these secondary complications, together with the substantial risk of liver damage, the objective of this review was to research and suggest, based on the scientific evidence, the appropriate clinical use of drugs with direct antiviral action (AAD) according to the criteria of international medical organizations. This is to maximize the clinical benefits for patients and to facilitate access to DAA therapy for all patients with chronic hepatitis C. According to the WHO, no vaccine is currently available, and therapies using new antivirals and their combinations are now an effective and safer solution for patients than they have been in the past with the use of interferons. This study aims to analyse the history and knowledge of the pathogenic biomolecular mechanisms and current therapies for HCV. Full article

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms. We aimed to identify overlapping mechanisms in MSCs derived from myeloid and lymphoid neoplasms contributing to disease progression and suppression of HSPCs to develop interventions that target these mechanisms. MSCs derived from healthy donors (n = 44) and patients diagnosed with myeloproliferative neoplasia (n = 11), myelodysplastic syndromes (n = 16), or acute myeloid leukemia (n = 25) and B-Non-Hodgkin lymphoma (n = 9) with BM infiltration and acute lymphoblastic leukemia (n = 9) were analyzed for their functionality and by RNA sequencing. A reduced growth and differentiation capacity of MSCs was found in all entities. RNA sequencing distinguished both groups but clearly showed overlapping differentially expressed genes, including major players in the BMP/TGF and WNT-signaling pathway which are crucial for growth, osteogenesis, and hematopoiesis. Functional alterations in healthy MSCs were inducible by exposure to supernatants from malignant cells, implicating the involvement of these factors in disease progression. Overall, we were able to identify overlapping factors that pose potential future therapeutic targets. Full article

Our aim was to determine the secondary antibody deficiency (SAD) profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, and clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin’s lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%, chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG < 400 mg/dL in 60.0%, IgA < 40 mg/dL in 55.0%, and CD19 < 20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 3.0% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (p = 0.0001). Most patients progressed to hypo-γ-globulinemia and SAD after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases; therefore, monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement. Full article

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin’s lymphoma. Full article

Background: Lymphomas account for approximately 10% of all cancer cases among the Saudi population. Even when separated, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are in the top ten most commonly diagnosed cancers among Saudi men and women. Despite the substantial cost of HL and NHL to public health, the resources to assess their impact are insufficient. This study provides a two-decade detailed assessment of lymphoma incidence trends in the Saudi population. Methods: Analysis of the Saudi Cancer Registry (SCR) data for various incidence metrics from 2001 to 2020 was conducted. Joinpoint regression analysis was further performed to investigate temporal trends globally and by age group, gender, and administrative region. Results: HL cases grew by 174.1%, whereas NHL cases increased by only 80% for that time period. The HL overall Age-Standardized Incidence Rate (ASR) increased by 100% for both genders combined but remained unchanged for NHL. The median age at diagnosis for HL (20–30 years) and NHL (46–57 years) was lower than in many other nations. Our model identified increasing trends for HL with annual percentage changes (APCs) of 2.94% (CI: 2.2–3.7) and 3.67% (CI: 2.6–4.7) for males and females, respectively. The rise was mainly among young groups under 40. On the contrary, the NHL cohort revealed notable declining tendencies. We discovered alarming rates of HL in Saudi Arabia’s APC (2.23% for males and 3.88% for females) and ASR compared to other Western countries. Overall, the majority of the patients presented with advanced-stage disease at a younger age and with slight male predominance. Conclusions: The overall incidence of lymphoma (especially HL) has been rising among Saudis. Implementation of secondary and tertiary prevention measures, as well as management of modifiable risk factors, is warranted. Full article

Hodgkin lymphomas are radiosensitive and curable tumors that often involve the mediastinum. However, the application of radiation therapy to the mediastinum is associated with late effects including cardiac and pulmonary toxicities and secondary cancers. The adoption of conformal IMRT and deep inspiration breath- hold (DIBH) can reduce the dose to healthy normal tissues (lungs, heart and breast). We compared the dosimetry of organs at risk (OARs) using different IMRT techniques for two breathing conditions, i.e., deep inspiration breath hold (DIBH) and free breathing. Twenty-three patients with early-stage mediastinal Hodgkin lymphomas were accrued in the prospective study. The patients were given treatment plans which utilized full arc volumetric modulated arc therapy (F-VMAT), Butterfly VMAT (B-VMAT), and fixed field IMRT (FF-IMRT) techniques for both DIBH and free breathing methods, respectively. All the plans were optimized to deliver 95% of the prescription dose which was 25.2 Gy to 95% of the PTV volume. The mean dose and standard error of the mean for each OAR, conformity index (CI), and homogeneity index (HI) for the target using the three planning techniques were calculated and compared using Student’s t-test for parametric data and Wilcoxon signed-rank test for non-parametric data. The HI and CI of the target was not compromised using the DIBH technique for mediastinal lymphomas. The mean values of CI and HI for both DIBH and FB were comparable. The mean heart doses were reduced by 2.1 Gy, 2.54 Gy, and 2.38 Gy in DIBH compared to FB for the F-VMAT, B-VMAT, and IMRT techniques, respectively. There was a significant reduction in V5Gy, V10Gy, and V15Gy to the heart (p < 0.005) with DIBH. DIBH reduced the mean dose to the total lung by 1.19 Gy, 1.47 Gy, and 1.3 Gy, respectively. Among the 14 female patients, there was a reduction in the mean right breast dose with DIBH compared to FB (4.47 Gy vs. 3.63 Gy, p = 0.004). DIBH results in lower heart, lung, and breast doses than free breathing in mediastinal Hodgkin Lymphoma. Among the different IMRT techniques, FF-IMRT, B-VMAT, and F-VMAT showed similar PTV coverage, with similar conformity and homogeneity indices. However, the time taken for FF-IMRT was much longer than for the F-VMAT and B-VMAT techniques for both breathing methods. B-VMAT and F-VMAT emerged as the optimal planning techniques able to achieve the best target coverage and lower doses to the OARs, with less time required to deliver the prescribed dose. Full article

Eosinophils in peripheral blood account for 0.3–5% of leukocytes, which is equivalent to 0.05–0.5 × 10⁹/L. A count above 0.5 × 10⁹/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 10⁹/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia. Full article