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

Recruiting

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

• Registration Number: NCT05931718
• Lead Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

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.

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 Timeline

• Study Start: 2019-06-01
• Study First Submitted: 2023-05-29
• Study First Submitted QC: 2023-07-03
• Study First Posted: 2023-07-05
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-08
• Last Update Posted: 2024-10-11
• Primary Completion: 2030-09
• Study Completion: 2035-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Autoimmune hemolytic anemia	NGS	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).
Autoimmune hemolytic anemia	Fecal microbiome	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).
Immune thrombocytopenia	cytokine essays	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).
Immune thrombocytopenia	NGS	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).
Immune thrombocytopenia	Fecal microbiome	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).
Myelodysplastic syndromes	NGS	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.
Chronic idiopathic neutropenia/Autoimmune neutropenia	cytokine essays	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).
Autoimmune hemolytic anemia	cytokine essays	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).
Chronic idiopathic neutropenia/Autoimmune neutropenia	NGS	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).
Myelodysplastic syndromes	Fecal microbiome	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.
Immune thrombocytopenia	Thrombopoietin Receptor Agonist	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).
Chronic idiopathic neutropenia/Autoimmune neutropenia	Fecal microbiome	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).
Myelodysplastic syndromes	cytokine essays	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.
Chronic idiopathic neutropenia/Autoimmune neutropenia	G-CSF	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).
Autoimmune hemolytic anemia	Erythropoietin	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).
Myelodysplastic syndromes	Luspatercept	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.

Primary Outcome Measures

Name	Time	Method
specificity of autoantibody testing in autoimmune cytopenias	2021-2026	to define the specificity of autoantibody testing in autoimmune cytopenias
sensitivity of autoantibody testing in autoimmune cytopenias	2021-2026	to define the sensitivity of autoantibody testing in autoimmune cytopenias
sensitivity of bone marrow trephine in autoimmune cytopenias	2021-2026	to define the sensitivity of bone marrow trephine in autoimmune cytopenias

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico; 🇮🇹 Milano, Italy