Active clinical trials for "Anemia, Hemolytic, Autoimmune"

The goal of this observational study is to characterize the diagnostic and therapeutic management of autoimmune cytopenias including autoimmune hemolytic anemia, immune thrombocytopenia, and chronic idiopathic/autoimmune neutropenia. The main aims to answer are: evaluation of traditional and novel diagnostic tools including immunohematology, cytokine essays, bone marrow studies, molecular findings, and fecal microbiome. evaluation of type and sequence of the therapies administered, the response rates, and the adverse events. evaluation of clinical and laboratory (immunologic, molecular, and morphologic) predictors of outcome. evolution of autoimmune cytopenias into myelodysplastic syndromes. a subgroup of patients with myelodysplastic syndromes will be included to evaluate the presence of immunologic events, autoimmune activation, and red cell metabolism. Participants will receive a clinical/laboratory diagnostic workup as per current clinical practice. Furthermore They will be sampled at baseline (peripheral blood and feces for microbiome) and followed up for at least 3 years to evaluate their clinical course, therapeutic management and outcome.

Cold agglutinin disease (CAD) is defined as a chronic autoimmune hemolytic anemia (AIHA) with a monospecific direct antiglobulin test (DAT) strongly positive for C3d and the presence of cold agglutinins (CA; titer ≥ 64 at 4°C). Patients may have a B-cell clonal lymphoproliferative disorder (LPD) detectable in blood or marrow but no clinical or radiological evidence of malignancy. CAD can lead to AIHA, peripheral ischemic symptoms (cold-induced peripheral symptoms such as acrocyanosis etc.), or both. The CAs are typically monoclonal IgM antibodies produced by the clonal B-cells, usually IgM kappa with specificity for the I antigen on erythrocytes. There is no curative treatment. Current treatment options include rituximab monotherapy, however this has only a limited and short-lasting effect. Rituximab in combination with chemotherapy induces deeper and more durable responses, however since CAD patients typically do not have an overt malignancy this comes with concerns about short- and long-term toxicity. Novel complement inhibitors may be effective for the hemolysis but are not expected to be effective against cold induced peripheral symptoms while this is directly IgM mediated. Bruton Tyrosine Kinase inhibitors (BTKis) are effective in many B-cell lymphoproliferative disorders including the IgM producing clone of Waldenström macroglobulinemia (WM) and were very effective on both AIHA and peripheral ischemic symptoms in patients with CAD based on retrospective data.

Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by the destruction of red blood cells through warm or cold antibodies. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. Bruton's tyrosine kinase (BTK) plays a crucial role in the signaling pathway of B-cell receptor (BCR), and has been found to be a major source of pathogenic signal transduction for various lymphoproliferative malignancies. The activity of BTK is related to the occurrence and progression of various B-cell lymphomas. Currently, BTK inhibitors are widely used in the treatment of B-cell lymphomas, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), and other B-cell lymphomas, showing significant efficacy. BTK affects the production of messenger molecules and regulates the BCR signaling pathway, causing B cells to transform into self-reactive B cells, which can trigger autoimmune diseases. Current research has shown that BTK activity increases in several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) . Therefore, BTK inhibitors (BTKi) are important for the treatment of autoimmune diseases. Ibrutinib, one kind of BTKi, has been proven to treat secondary autoimmune hemolytic anemia (AIHA) in CLL and control CLL progression, and is an effective drug for treating lymphoma-associated AIHA . One kind of second-generation selective BTKi, acalabrutinib, can also reduce the incidence of AIHA in relapsed or refractory CLL patients. Currently, phase-II clinical studies exploring the treatment of AIHA using Ibrutinib, acalabrutinib, and rilzabrutinib, another BTKi, are underway. Zanubrutinib (BGB-3111, Brukinsa®, BeiGene) is a second-generation irreversible BTKi developed by Chinese company BeiGene. Compared to Ibrutinib, zanubrutinib has shown stronger effective activity and higher selectivity towards BTK, and weaker effects on other targets such as TEC, EGFR, and Src families, with low off-target side effects. Its efficacy, durability, oral absorption, and targeting are better than those of Ibrutinib. Zanubrutinib is approved for the treatment of various B-cell lymphomas, and clinical trials have shown excellent efficacy and tolerability in CLL and WM patients. In previously treated CLL patients, zanubrutinib exhibits better efficacy and safety than Ibrutinib. Currently, phase II clinical studies of zanubrutinib in ITP, antiphospholipid syndrome, IgG4-related immune diseases, and active proliferative lupus nephritis are underway. The therapeutic effect of zanubrutinib on refractory warm autoimmune hemolytic anemia, is worth exploring through exploratory research.

The sample size of this study is calculated based on Simon's two-stage design. The first stage of the study enrolled a cohort of 12 patients. If after 12 weeks at least 6 patients achieved a response, then enrollment was expanded to a total of 26 patients. The null hypothesis was unaccepted if more than 14 of 26 patients achieved the response. Accounting for a 20% dropout rate, the estimated final sample size was 33 patients.

In autoimmune hemolytic anemia (AIHA) auto-antibodies directed against red blood cells (RBCs) lead to increased RBC clearance (hemolysis). This can result in a potentially life-threatening anemia. AIHA is a rare disease with an incidence of 1-3 per 100,000 individuals. An unsolved difficulty in diagnosis of AIHA is the laboratory test accuracy. The current 'golden standard' for AIHA is the direct antiglobulin test (DAT). The DAT detects autoantibody- and/or complement-opsonized RBCs. The DAT has insufficient test characteristics since it remains falsely negative in approximate 5-10% of patients with AIHA, whereas a falsely positive DAT can be found in 8% of hospitalized individuals. Also apparently healthy blood donors can have a positive DAT. The consequences of DAT positivity are not well known and may point to early, asymptomatic disease, or to another disease associated with formation of RBC autoantibodies, such as a malignancy or (systemic) autoimmune disease. Currently, there are no guidelines to follow-up DAT positive donors. A second unsolved difficulty is the choice of treatment in AIHA. Hemolysis can be stopped or at least attenuated with corticosteroids, aiming to inhibit autoantibody production and/or RBC destruction. Many patients do not respond adequately to corticosteroid treatment or develop severe side effects. Currently, it is advised to avoid RBC transfusions since these may lead to aggravation of hemolysis and RBC alloantibody formation. But in case symptomatic anemia occurs, RBC transfusions need to be given. An evidence-based transfusion strategy for AIHA patients is needed to warrant safe transfusion in this complex patient group. To design optimal diagnostic testing and (supportive) treatment algorithms, the investigators will study a group well-characterized patients with AIHA and blood donors without AIHA, via a prospective centralized clinical data collection and evaluation of new laboratory tests. With this data the knowledge of the AIHA pathophysiology and to evaluate diagnostic testing in correlation with clinical features and treatment outcome can be improved.

This is a multicenter, single arm, phase II study aimed at evaluating ibrutinib therapy for the treatment of AIHA in patients with CLL/SLL or CLL-like MBL.

Prospective registry study for children and young adults with severe immune cytopenias (persisting/chronic immune thrombocytopenia, autoimmune hemolytic anemia, and Evans syndrome) to improve the management, facilitate the differential diagnostic work-up, and document the clinical course under various treatments. Time points: at inclusion, after 6 months, after 12 months, then yearly up to 4 years after inclusion. No intervention, mere observation and documentation. Guided pre-inclusion (differential) diagnostic work-up.

From 2004, OBS'CEREVANCE is a national real-world prospective clinical cohort of patients with auto-immune cytopenia of pediatric-onset : Immune thrombocytopenia (ITP), Autoimmune Hemolytic anemia (AIHA), or Evans syndrome (all bi or tri cytopenias). Thanks to the collaboration of the 30 French pediatric hematologic centers, this cohort supports all of the Rare Disease Centre CEREVANCE (Centre de Référence National des Cytopénies Auto-Immunes de l'Enfant) missions for care, education and research. Specifically, this original unbiased database allows to describe the long-term health of adult patients, to identify the heterogenous genetic underlying pathophysiologic contexts, and to study the benefit-risk balance of treatments, including the growing development of targeted therapies.

The Internal Medicine Department of Haut-Lévêque Hospital (Pr E LAZARO, Pr JL PELLEGRIN, Pr JF VIALLARD) was accredited in 2017 by the Ministry of Health as a Constitutive Reference Center for Autoimmune Cytopenia. The investigators wish to launch new research projects in autoimmune cytopenia and propose a translational and fundamental research based on collaboration between the clinical department, the biological resource center and the CNRS and INSERM research units ("Bedside to the Bench Strategy"). Thus, in the perspective of future research work, it seems imperative to set up a biological bank for the patients followed in our Reference Center.

CARMEN is a national, real-world clinical registry of all adult patients with incident diagnosis of Immune thrombocytopenia (ITP) or Autoimmune Hemolytic anemia (AIHA) patients in France. It is aimed at describing ITP and AIHA clinical features, assessing the real-world risk-benefit ratio of treatments and adherence to guidelines for ITP and AIHA management.