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

Sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico (Other)

Overall Status

Recruiting

CT.gov ID

NCT05931718

Collaborator

(none)

200

Enrollment

Location

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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.

Actual Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

sensitivity of autoantibody testing in autoimmune cytopenias [2021-2026]
to define the sensitivity of autoantibody testing in autoimmune cytopenias
specificity of autoantibody testing in autoimmune cytopenias [2021-2026]
to define the specificity 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

overall response rate [2021-2026]
to define response rates to treatment of autoimmune cytopenias and myelodysplastic syndromes
Evaluation of somatic mutations [2021-2026]
to define somatic mutations in autoimmune cytopenias and myelodysplastic syndromes by NGS
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
Single cell RNA expression [2021-2026]
to define bone marrow composition by single cell analysis in autoimmune cytopenias and myelodysplastic syndromes
Evaluation of cytokine levels [2021-2026]
to define cytokine levels in autoimmune cytopenias and myelodysplastic syndromes by ELISA

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.