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Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation.

The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing gra

Guarding the heart in the era of immunotherapies: insights for cardio-oncology practice.

The advent of cancer immunotherapies, including immune checkpoint inhibitors (ICI), Chimeric antigen receptor (CAR-T) cell therapies, and bispecific antibodies and other immune-activating platforms such as therapeutic vaccines and oncolytic viruses (often used in combination regimens) has revolutionized oncology by improving patient outcomes across diverse malignancies. However, these therapies are increasingly linked to cardiovascular toxicities such as myocarditis, arrhythmias, and heart failure, posing significant clinical challenges. Here we review current evidence on the mechanisms, clini

Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft

Monocyte engraftment dynamics and flow cytometric analysis in allogeneic and autologous peripheral blood stem cell transplantation: a prospective study.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) success relies on timely engraftment and immune reconstitution. While neutrophil and platelet recovery are well-established clinical endpoints, the dynamics of monocyte engraftment and their relationship with hematopoietic recovery remain insufficiently characterized. METHODS: In this prospective observational study, 56 patients undergoing autologous (n = 32) or allogeneic (n = 24) peripheral blood stem cell transplantation were enrolled. Pre-engraftment monocyte peak day was defined based on serial complete blood counts. Flow cytomet

Half a century of healing: celebrating the 50th anniversary of EBMT.

EBMT is a non-profit organization with a clear mission: "to save the lives of patients with blood cancers and other life-threatening diseases by advancing the fields of blood and marrow transplantation and cell therapy worldwide through science, education and advocacy". In 1974, EBMT was established by European physicians in St. Moritz to share bone marrow transplantation (BMT) experiences and foster collaboration. Founding members included Jon Van Rood, Bruno Speck, and Eliane Gluckman. By 1989, the group expanded significantly, emphasizing mutual trust and collaboration. EBMT played a crucia

Risk Stratification of Non-Relapse Mortality After Allogeneic Hematopoietic Stem Cell Transplantation Based on Pre-Transplant Sarcopenia and HCT-CI.

Non-relapse mortality (NRM) remains a major and often unavoidable adverse event following allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly among older adults and patients with multiple comorbidities. Although the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) is widely used for risk assessment, its predictive performance for NRM is limited, particularly for capturing functional status and physiological reserve. Sarcopenia, a marker of physical frailty and reduced physiological reserve, has recently emerged as a potential prognostic marker in

Autologous Hematopoietic Cell Transplant as an Effective Treatment Modality for Systemic Sclerosis and Multiple Myeloma.

Systemic sclerosis (SSc) is a multi-system disease characterized by a dysregulated immune system. Autologous hematopoietic cell transplantation (AHCT) is the only treatment that has been shown to confer significant benefit in controlling disease and improving survival for patients with SSc. A diagnosis of multiple myeloma (MM) after the diagnosis of SSc is rare and optimal treatment in such cases remains unclear. We here report a case of a female patient who was diagnosed with MM while she was undergoing evaluation for AHCT due to SSc. A novel conditioning regimen for AHCT, with therapeutic ef

Daratumumab for PRCA after HCT: study and practical considerations from the EBMT Transplant Complications Working Party.

Pure red cell aplasia (PRCA) is a relevant complication after ABO-mismatched allogeneic hematopoietic cell transplantation (HCT). No standard treatment exists, and practice is heterogenous. In this study, we took advantage of an international collaboration to describe characteristics and outcomes of patients receiving daratumumab for PRCA following first allogeneic HCT. We identified 45 patients meeting these criteria (median patient age, 56 years). The median time from HCT to PRCA was 55 days (IQR, 36-116) and all patients were transfusion-dependent at time of daratumumab start. Daratumumab w

Non-infectious pulmonary complications after haematopoietic progenitor transplantation: a diagnostic approach.

Haematopoietic stem cell transplantation (HCT) is an established treatment for a wide variety of haematological diseases, both malignant and non-malignant. Infectious and non-infectious post-HCT pulmonary complications are a major cause of morbidity and mortality, with non-infectious complications becoming more prominent in recent decades as prophylaxis has led to a decrease in infectious complications. Globally, these complications can be divided into three phases (neutropenic, early and late phase) depending on their time of onset in relation to the graft. There is a growing awareness that t

Case report: Daratumumab treatment in pre-transplant alloimmunization and severe hemolytic anemia.

Daratumumab, a CD38 monoclonal antibody that has been FDA-approved to treat multiple myeloma, has acquired popularity and is used off-label for both auto- and alloantibody mediated disorders, particularly in refractory/resistant circumstances. Much of the published data for its use in pediatric blood disorders has been in post-transplant autoimmune cytopenias. Here we describe three patients in whom daratumumab was used outside of post-transplant autoimmune cytopenias, highlighting further potential uses of this medication.

Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

Совпадение в полном тексте источника
… PD-1 is expressed on immature thymocytes, activated CD4 and CD8+ T cells, B cells, dendritic cells, and natural killer (NK) cells. … CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat Immunol. (2005) 6:152–62. doi: 10.1038/ni1160 114. DeBenedette MA, Shahinian A, Mak TW, Watts TH. Costimulation of CD28- T lymphocytes by 4-1BB ligand. …

Burden of Seasonal Human Coronavirus Infections in Hematopoietic Cell Transplant Recipients.

BackgroundCommunity respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.MethodsWe performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respirato

Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity.

BackgroundThe introduction of posttransplant cyclophosphamide (PTCy) is one of the major achievements in the field of haploidentical stem cell transplantation (haplo-HCT). The transplant conditioning intensity (TCI) score is a refined classification of conditioning regimens that assigns weight scores to conditioning regimen components. The aim of our analysis was twofold: to assess the effect on transplant outcomes of combining PTCy with calcineurin inhibitor + mycophenolate mofetil (MMF) instead of mTOR inhibitor + MMF for GvHD prophylaxis, and to assess the effect of stratification by condit

Новое развитие аутоиммунного расстройства после лечения иммунной реконституции при множественном склерозе.

Иммунная реконституционная терапия (IRT) является относительно новым и высокоэффективным средством лечения множественного склероза (MS). Неопределенность в отношении развития аутоиммунных расстройств (АД) после сохранения некоторых методов лечения. Цель этого исследования состояла в том, чтобы провести оценку новых разработок в области АД после IRT у пациентов с РС и описать характер этих АД и время их начала. В исследование было включено в общей сложности 179 пациентов с множественным склерозом (37 после аналоговой трансплантации гематопоэтических стволовых клеток (АХСТ), 19 пациентов после а

Prognostic Factors on the Graft-versus-Host Disease-Free and Relapse-Free Survival after Adult Allogeneic Hematopoietic Stem Cell Transplantation.

The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD), relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS) in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus,

Comparison of Three Distinct Prophylactic Agents Against Invasive Fungal Infections in Patients Undergoing Haplo-identical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide.

Over the past decade, invasive fungal infections (IFIs) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to bedetermined. We conducted a retrospective analysis, comparing the safety and efficacy of micafungin 50mg/day vs. fluconazole 400mg/day vs. itraconazole 200mg/day as prophylaxis for adult patients with various haematological diseases receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) followed by high-dose cyclophosphamide (P

Pleuropulmonary Changes Induced by Drugs in Patients with Hematologic Diseases

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Клеточная терапия в многоразовом склерозе: Клинические достижения, ограничения и перспективы на будущее из клинических исследований - систематический обзор.

Фон: Множественный склероз (MS) — хроническое аутоиммунное демиелинирующее заболевание центральной нервной системы (CNS), характеризующееся воспалением, обезвоживанием и прогрессивным нейродегенерацией. Несмотря на то, что нынешняя медикаментозная терапия (ДМТ) может снизить частоту рецидивов и провокационной активности, они редко останавливают долгосрочное развитие или устраняют неврологические повреждения. В последние годы клеточная терапия стала многообещающим подходом к содействию иммунальному регулированию и нейрогенерации в MS. Методы: Настоящий обзор резюмирует текущие клинические данны

Co-infusion of mesenchymal stromal cells to prevent GVHD after allogeneic hematopoietic cell transplantation from HLA-mismatched unrelated donors after reduced-intensity conditioning: a double-blind randomized study and literature review.

BackgroundMesenchymal stromal cells (MSC) have immunomodulatory and hematopoiesis-supporting properties that could potentially benefit hematopoietic stem cell (HSC) engraftment and decrease the incidence and/or severity of graft-versus-host disease (GVHD).MethodsBased on our previous pilot study, we established a multicenter, prospective, randomized, double-blind trial evaluating the efficacy of co-infusing third-party MSC (1.5-3 × 106/kg) versus placebo on the day of HSC transplantation (HCT) to prevent GVHD in recipients of HLA-mismatched unrelated donors after reduced-intensity conditioning