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Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma.

Clinical success with intravenous (IV) oncolytic virotherapy (OV) has to-date been anecdotal. We conducted a phase 1 clinical trial of systemic OV and investigated the mechanisms of action in responding patients. A single IV dose of vesicular stomatitis virus (VSV) interferon-β (IFN-β) with sodium iodide symporter (NIS) was administered to patients with relapsed/refractory hematologic malignancies to determine safety and efficacy across 4 dose levels (DLs). Correlative studies were undertaken to evaluate viremia, virus shedding, virus replication, and immune responses. Fifteen patients receive

Цитоплания и инфекция после цитакабагена автолейкеля в сильно обработанном реанимированном или рефрактном миеломе.

В феврале Управление по контролю за продуктами питания и лекарственными препаратами одобрило автолекцию Ciltaakabtagene (cilta-cel). 2022 для лечения повторной/реактивной множественной миэломы после four циклы терапии. По поводу CARTITUDE-1 в ходе судебного разбирательства, ≥3 Широко распространены цитопентия и инфекции. Здесь мы пытались охарактеризовать цитопению и инфекцию после вливания цита-села в стандартную систему ухода. Это многоцентральное, ретроспективное исследование включало 105 - пациенты, получившие цилта-сел; 91 Днем 90 и 49 Днем 180 о последующей деятельности. Класс должности

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… CNS: central nervous system; GI: gastrointestinal; SSTI: skin and soft tissue infections; CMV: cytomegalovirus; COVID-19: coronavirus disease 2019; JC virus: human polyomavirus 2; RSV: respiratory syncytial virus; VZV: varicella-zoster virus (shingles). …

HTLV-1 viral oncogene HBZ induces osteolytic bone disease in transgenic mice.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell malignancy that occurs in HTLV-1 infected patients. Most ATL patients develop osteolytic lesions and hypercalcemia of malignancy, causing severe skeletal related complications and reduced overall survival. The HTLV-1 virus encodes 2 viral oncogenes, Tax and HBZ. Tax, a transcriptional activator, is critical to ATL development, and has been implicated in pathologic osteolysis. HBZ, HTLV-1 basic leucine zipper transcription factor, promotes tumor cell proliferation and disrupts Wnt pathway modulators; however, its role in ATL induced o

Epidemiology of infections in cancer patients.

Although major advances in the care of cancer patients over the past several decades have resulted in improved survival, infectious complications remain a significant cause of morbidity and mortality. To successfully identify, treat, and prevent infections, a comprehensive understanding of risk factors that predispose to infection and of commonly encountered pathogens is necessary. In addition, clinicians must keep abreast of the changing epidemiology of infections in this population. As therapeutic modalities continue to evolve, as established pathogens become increasingly drug resistant, and

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… More recently, progressive multifocal leukoencephalopathy (PML) caused by JC virus has been described in CLL patients treated with the purine analog fludarabine and with various monoclonal antibodies [ 215 ]. …

Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.

BACKGROUND: Cancer represents a major global public health issue, and recent research has focused on improving the efficacy of existing therapeutic approaches. In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment-resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance. MAIN BODY: Combination-based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have b

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

Interleukin-32: a Pandora's box in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), has been estimated to infect around 40.8 million people globally. This virus can persist and thrive in the presence of antiretroviral therapy, which is a major obstacle to HIV eradication. Therefore, understanding host immunological factors that underlie HIV persistence and pathogenesis can lead to the development of immunotherapeutic interventions. Interleukin-32 (IL-32) is an orphan cytokine with multiple isoforms and a complex signal transduction pathway that transmits through non-specific receptors.

A systematic review and meta-analysis of herpes zoster risk in adults with immunocompromised conditions and autoimmune diseases in Asia-Pacific.

Asia-Pacific (APAC) faces an increasing burden of herpes zoster (HZ) over time. The risk of HZ and its complications are increased in immunocompromised (IC) patients and those with autoimmune diseases (AID). Our study aimed to synthesize evidence on the epidemiological burden of HZ and its complications among the general adult population and patients with IC/AID conditions in APAC. Following a systematic literature review, we performed meta-analyses for outcomes where ≥3 studies met the inclusion criteria. Of the 271 articles identified, 75 were included for meta-analysis. We found a high burd

The use of validated and nonvalidated surrogate endpoints in two European Medicines Agency expedited approval pathways: A cross-sectional study of products authorised 2011-2018.

BACKGROUND: In situations of unmet medical need or in the interests of public health, expedited approval pathways, including conditional marketing authorisation (CMA) and accelerated assessment (AA), speed up European Medicines Agency (EMA) marketing authorisation recommendations for medicinal products. CMAs are based on incomplete benefit-risk assessment data and authorisation remains conditional until regulator-imposed confirmatory postmarketing measures are fulfilled. For products undergoing AA, complete safety and efficacy data should be available, and postauthorisation measures may includ

Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation.

Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia.

Secondary immunodeficiency is reported in most patients with hematological malignancies such as chronic lymphocytic leukemia and multiple myeloma. The aim of our review was to evaluate the existing literature data on patients with hematological malignancies, with regard to the effect of immunodeficiency on the outcome, the clinical and therapeutic approach, and on the onset of noninfectious complications, including thrombosis, pleural effusion, and orofacial complications. Immunodeficiency in these patients has an intense impact on their risk of infection, in turn increasing morbidity and mort

Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

Cryoglobulinemia: An update on classification, pathophysiology, clinical presentation, and management.

Cryoglobulinemia (CG) is defined by the presence of serum immunoglobulins that precipitate below 37°C and redissolve upon rewarming. It is classified into three types based on immunoglobulin composition. Type I, a rare form, involves monoclonal IgM or IgG and is linked to lymphoproliferative disorders. Types II and III are known as mixed CG (MC): Type II consists of polyclonal IgG and monoclonal IgM with rheumatoid factor (RF) activity, whereas Type III includes polyclonal IgG and polyclonal IgM with RF activity. MC is predominantly associated with hepatitis C virus (HCV) infection and involve

Hepatitis B virus-infection related cryoglobulinemic vasculitis. Clinical manifestations and the effect of antiviral therapy: A review of the literature.

OBJECTIVE: Hepatitis B virus (HBV) infection causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Furthermore, about 20% of the patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV), polyarteritis nodosa, non-rheumatoid arthritis, glomerulonephritis and non-Hodgkin lymphoma. This review analyzed literature data on clinical manifestations of HBV-related CV and the impact of antiviral therapy with analoques nucleotide. METHODS: A PubMed search was performed to select eligible studies in the literature, up to July 2022. RESULTS: Some studies have an

Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term wi

Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy.

Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are prone to present with antibody production deficits associated with recurrent or severe bacterial infections that might benefit from human immunoglobulin (Ig) (IVIg/SCIg) replacement therapy. However, the original IVIg trial data were done before modern therapies were available, and the current indications do not take into account the shift in the immune situation of current treatment combinations and changes in the spectrum of infections. Besides, patients affected by other B cell malignancies present with similar i

Clinicopathological features and prognostic factors of AIDS-related lymphoma: a retrospective single-center study in China.

AIDS-related lymphoma (ARL) is a leading cause of mortality among people living with HIV (PLWH), characterized by distinct clinicopathological features and a generally poor prognosis. However, comprehensive studies on ARL remain limited. This study aimed to evaluate the clinicopathological characteristics, immune status, and Epstein-Barr virus (EBV)/HIV viral loads in PLWH diagnosed with lymphoma, and to assess their prognostic significance. A retrospective analysis was conducted on 130 ARL cases diagnosed between 2017 and 2024. The cohort included 56 Burkitt lymphoma (BL), 51 diffuse large B-

Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive life-threatening disease that consists of uncontrolled activated lymphocytes and macrophages that secrete excessive cytokines. Symptoms and laboratory findings of HLH include prolonged fever, cytopenia, hepatosplenomegaly, liver dysfunction, hypertriglyceridemia, hyperferritinemia, increased soluble interleukin-2 receptor, low fibrinogen, and neurological problems. HLH has two forms: primary (familial autosomal recessive) or secondary (related to infections, malignancy, autoimmune and metabolic disorders, transplantations, chimeric anti

Эффективность и инфекционные осложнения BCMA T-клеток в лечении множественной миеломы: реальные данные из Швеции.

Множественная миелома (ММ), неизлечимая болезнь, характеризующаяся частыми рецидивами и потребностью в нескольких видах лечения, часто становится устойчивым к рецидиву/изъятию всех имеющихся лекарств и лекарственных препаратов. В качестве эффективных методов лечения MM появились антитела, в частности BCMA T-клетки, демонстрирующие впечатляющую эффективность. Однако такое лечение может отрицательно сказаться на иммунной системе, повышая уязвимость к инфекциям. 58 Шведские пациенты с плохим прогнозом MM. Пациенты показали: 69% Общий коэффициент представления ответов, с 69% выживание и 60% Выжива

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… Opportunistic infections included pneumocystis jiroveci pneumonia (PJP), pseudomonas, legionella, moraxella, and progressive multifocal leukoencephalopathy (PML), which was diagnosed after a brain biopsy revealed JC virus. …

Hematopoietic Tumors

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