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

Study Overview
=================
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.

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.

Conditions
-----------------
Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, Chronic Idiopathic Neutropenia, Autoimmune Neutropenia, Myelodysplastic Syndromes, Cold Agglutinin Disease

Intervention / Treatment
-----------------
* Biological: cytokine essays
* Biological: NGS
* Biological: Fecal microbiome
* Drug: Erythropoietin
* Drug: Luspatercept
* Drug: Thrombopoietin Receptor Agonist
* Drug: G-CSF


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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