Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia

NCT05931718 | Recruiting

• 1 other identifier: CYTOPAN
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autoimmune Hemolytic Anemia; Immune Thrombocytopenia; Chronic Idiopathic Neutropenia; Autoimmune Neutropenia; Myelodysplastic Syndromes; Cold Agglutinin Disease

Keywords

autoimmune hemolytic anemia; immune thrombocytopenia; chronic idiopathic neutropenia; autoimmune neutropenia; cold agglutinin disease; myelodysplastic syndromes; rituximab; thrombopoietin receptor agonists; erythropoietin; steroids; splenectomy; red cell metabolism; cytokines; luspatercept; microbiome; single cell analysis; next generation sequencing

Outcome Measures

Primary Outcomes (3)

• sensitivity of autoantibody testing in autoimmune cytopenias

  to define the sensitivity of autoantibody testing in autoimmune cytopenias

  2021-2026

• specificity of autoantibody testing in autoimmune cytopenias

  to define the specificity of autoantibody testing in autoimmune cytopenias

  2021-2026

• sensitivity of bone marrow trephine in autoimmune cytopenias

  to define the sensitivity of bone marrow trephine in autoimmune cytopenias

  2021-2026

Secondary Outcomes (6)

• overall response rate

  2021-2026

• Evaluation of somatic mutations

  2021-2026

• Evaluation of pyruvate kinase activity

  2021-2026

• Evaluation of microbiome

  2021-2026

• Single cell RNA expression

  2021-2026

Study Arms (4)

Autoimmune hemolytic anemia

AIHA patients will be enrolled at diagnosis and stratified according to AIHA type (i.e. warm, cold, mixed, and atypical forms), sampled for peripheral blood for cytokine and NGS studies, and for feces for microbiome studies. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected. Patients will be followed up to collect treatments, responses, relapses, and complications (particularly thromboses and infections).

Biological: cytokine essays; Biological: NGS; Biological: Fecal microbiome; Drug: Erythropoietin

Immune thrombocytopenia

ITP patients will be enrolled at diagnosis and sampled for peripheral blood for cytokine and NGS studies, and for feces for microbiome studies. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected.Patients will be followed up to collect treatments, responses, relapses, and complications (particularly thromboses and infections).

Biological: cytokine essays; Biological: NGS; Biological: Fecal microbiome; Drug: Thrombopoietin Receptor Agonist

Chronic idiopathic neutropenia/Autoimmune neutropenia

CIN/AIN patients will be enrolled at diagnosis and sampled for peripheral blood for cytokine and NGS studies, and for feces for microbiome studies. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected.Patients will be followed up to collect treatments, responses, relapses, and complications (particularly infections).

Biological: cytokine essays; Biological: NGS; Biological: Fecal microbiome; Drug: G-CSF

Myelodysplastic syndromes

MDS patients will be enrolled at diagnosis and sampled for peripheral blood for cytokine and NGS studies, and to evaluate red cell metabolism. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected. Patients will be followed up to collect treatments, responses, relapses, and outcome.

Biological: cytokine essays; Biological: NGS; Biological: Fecal microbiome; Drug: Luspatercept

Interventions

cytokine essays BIOLOGICAL

evaluation of immunomodulatory cytokines by ELISA kits on peripheral blood samples

Autoimmune hemolytic anemia; Chronic idiopathic neutropenia/Autoimmune neutropenia; Immune thrombocytopenia; Myelodysplastic syndromes

NGS BIOLOGICAL

evaluation of somatic mutations commonly associated with myeloid neoplasm and immunodeficiencies by next generation sequencing on peripheral blood samples

Autoimmune hemolytic anemia; Chronic idiopathic neutropenia/Autoimmune neutropenia; Immune thrombocytopenia; Myelodysplastic syndromes

Fecal microbiome BIOLOGICAL

evaluation of fecal microbiome on fecal samples

Autoimmune hemolytic anemia; Chronic idiopathic neutropenia/Autoimmune neutropenia; Immune thrombocytopenia; Myelodysplastic syndromes

Erythropoietin DRUG

evaluation of recombinant erythropoietin use, safety and efficacy in patients with autoimmune hemolytic anemia according to clinical practice

Autoimmune hemolytic anemia

Luspatercept DRUG

evaluation of cytokine levels, molecular profile and bone marrow microenvironment by single cell analysis in patients treated with luspatercept according to clinical practice

Myelodysplastic syndromes

Thrombopoietin Receptor Agonist DRUG

evaluation of TPO-RA use, safety and efficacy in patients with ITP according to clinical practice

Immune thrombocytopenia

G-CSF DRUG

evaluation of G-CSF use, safety and efficacy in patients with CIN/AIN according to clinical practice

Chronic idiopathic neutropenia/Autoimmune neutropenia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with anemia (Hb \<12 g/dL), thrombocytopenia (PLT\<100.000/mmc) and/or neutropenia (neutrophils\<1000/mmc) attending the inpatient or outpatient facility of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Cytopenia diagnosis will be based on current guidelines for AIHA (evidence of hemolysis and positive direct Coombs test or negative once excluded other causes), for ITP (exclusion of other thrombocytopenia causes) and for CIN/AIN (exclusion of other neutropenia causes). Patients will be classified according to the degree of the cytopenia and, for AIHA, according to thermal characteristics (warm, cold, mixed, atypical). For the substudy of patients with MDS patients will be stratified according to WHO 2022 classification of myeloid neoplasms.

You may qualify if:

• Diagnosis of autoimmune cytopenias (AIHA/ITP/CIN/AIN)
• age \>/= 18 years
• ability to sign informed consent
• availability to undergo 3 year follow up
• for the subgroup of patients with myelodysplastic syndrome: bone marrow evaluation showing \>/= 10% dysplastic features of at least one lineage along with MDS defining cytopenia and/or MDS defining cytogenetics.

You may not qualify if:

• any condition impeding the acquisition of the informed consent
• immune cytopenia diagnosis preceding \>/= 6 months the enrolment

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico

Milan, 20100, Italy

RECRUITING

Related Publications (2)

• Fattizzo B, Pedone GL, Brambilla C, Pettine L, Zaninoni A, Passamonti F, Barcellini W. Recombinant erythropoietin in autoimmune hemolytic anemia with inadequate bone marrow response: a prospective analysis. Blood Adv. 2024 Mar 12;8(5):1322-1327. doi: 10.1182/bloodadvances.2023011798.

  PMID: 38029356 DERIVED

• Versino F, Revelli N, Villa S, Pettine L, Zaninoni A, Prati D, Passamonti F, Barcellini W, Fattizzo B. Transfusions in autoimmune hemolytic anemias: Frequency and clinical significance of alloimmunization. J Intern Med. 2024 Mar;295(3):369-374. doi: 10.1111/joim.13753. Epub 2023 Nov 27.

  PMID: 38013593 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

peripheral blood for cytokines and next generation sequencing, bone marrow sample for single cell analysis, fecal sample for microbiome

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune; Purpura, Thrombocytopenic, Idiopathic; Myelodysplastic Syndromes

Interventions

Fecal Microbiota Transplantation; Erythropoietin; luspatercept; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2023
• First Posted: July 5, 2023
• Study Start: June 1, 2019
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): June 1, 2035
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)