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

Evaluation of the Diagnostic/Therapeutic Course of Patients With Autoimmune Cytopenias (Autoimmune Hemolytic Anemia AIHA, Immune Thrombocytopenia ITP, Chronic Idiopathic/Autoimmune Neutropenia CIN/AIN) and Identification of Predictive and Prognostic Markers.

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Immune Thrombocytopenia; Autoimmune Hemolytic Anemia; Cold Agglutinin Disease; Autoimmune Neutropenia; Chronic Idiopathic Neutropenia
• Intervention / Treatment: Biological: cytokine essays; Biological: NGS; Biological: Fecal microbiome; Drug: Erythropoietin; Drug: Thrombopoietin Receptor Agonist; Drug: G-CSF; Drug: Luspatercept

Detailed Description

This observational study will characterize the diagnostic and therapeutic management of autoimmune cytopenias including autoimmune hemolytic anemia, immune thrombocytopenia, and chronic idiopathic/autoimmune neutropenia to evaluate predictors of outcome. Additionally, a subgroup of patients with myelodysplastic syndromes (diagnosed according to current WHO 5th edition 2022) will be included to evaluate the presence of autoimmune activation, and red cell metabolism.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20100
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
    • Contact: Bruno Fattizzo, MD; Phone Number: +390255033477; Email: brunofattizzo@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; evaluation of immunomodulatory cytokines by ELISA kits on peripheral blood samples; Biological: NGS; evaluation of somatic mutations commonly associated with myeloid neoplasm and immunodeficiencies by next generation sequencing on peripheral blood samples; Biological: Fecal microbiome; evaluation of fecal microbiome on fecal samples; Drug: Erythropoietin; evaluation of recombinant erythropoietin use, safety and efficacy in patients with autoimmune hemolytic anemia according to clinical practice
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; evaluation of immunomodulatory cytokines by ELISA kits on peripheral blood samples; Biological: NGS; evaluation of somatic mutations commonly associated with myeloid neoplasm and immunodeficiencies by next generation sequencing on peripheral blood samples; Biological: Fecal microbiome; evaluation of fecal microbiome on fecal samples; Drug: Thrombopoietin Receptor Agonist; evaluation of TPO-RA use, safety and efficacy in patients with ITP according to clinical practice
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; evaluation of immunomodulatory cytokines by ELISA kits on peripheral blood samples; Biological: NGS; evaluation of somatic mutations commonly associated with myeloid neoplasm and immunodeficiencies by next generation sequencing on peripheral blood samples; Biological: Fecal microbiome; evaluation of fecal microbiome on fecal samples; Drug: G-CSF; evaluation of G-CSF use, safety and efficacy in patients with CIN/AIN according to clinical practice
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; evaluation of immunomodulatory cytokines by ELISA kits on peripheral blood samples; Biological: NGS; evaluation of somatic mutations commonly associated with myeloid neoplasm and immunodeficiencies by next generation sequencing on peripheral blood samples; Biological: Fecal microbiome; evaluation of fecal microbiome on fecal samples; Drug: Luspatercept; evaluation of cytokine levels, molecular profile and bone marrow microenvironment by single cell analysis in patients treated with luspatercept according to clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate	to define response rates to treatment of autoimmune cytopenias and myelodysplastic syndromes	2021-2026
Evaluation of somatic mutations	to define somatic mutations in autoimmune cytopenias and myelodysplastic syndromes by NGS	2021-2026
Evaluation of pyruvate kinase activity	to define pyruvate kinase activity in myelodysplastic syndromes	2021-2026
Evaluation of microbiome	to define microbiome composition in autoimmune cytopenias and myelodysplastic syndromes	2021-2026
Single cell RNA expression	to define bone marrow composition by single cell analysis in autoimmune cytopenias and myelodysplastic syndromes	2021-2026
Evaluation of cytokine levels	to define cytokine levels in autoimmune cytopenias and myelodysplastic syndromes by ELISA	2021-2026

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): June 1, 2035

Study Registration Dates

• First Submitted: May 29, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 5, 2023

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: rituximab; erythropoietin; cytokines; microbiome; steroids; next generation sequencing; autoimmune hemolytic anemia; myelodysplastic syndromes; immune thrombocytopenia; cold agglutinin disease; splenectomy; autoimmune neutropenia; luspatercept; chronic idiopathic neutropenia; thrombopoietin receptor agonists; red cell metabolism; single cell analysis
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms; Autoimmune Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Precancerous Conditions; Agranulocytosis; Leukopenia; Leukocyte Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Myelodysplastic Syndromes; Preleukemia; Neutropenia; Anemia; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Cytopenia; Hematinics; Epoetin Alfa; Luspatercept
• Other Study ID Numbers: CYTOPAN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No