Clinical trial NCT05931718: Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia
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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2023-07-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: sensitivity of autoantibody testing in autoimmune cytopenias
timeFrame: 2021-2026
measure: specificity of autoantibody testing in autoimmune cytopenias
timeFrame: 2021-2026
measure: sensitivity of bone marrow trephine in autoimmune cytopenias
timeFrame: 2021-2026
Secondary outcomes:
measure: overall response rate
timeFrame: 2021-2026
measure: Evaluation of somatic mutations
timeFrame: 2021-2026
measure: Evaluation of pyruvate kinase activity
timeFrame: 2021-2026
measure: Evaluation of microbiome
timeFrame: 2021-2026
measure: Single cell RNA expression
timeFrame: 2021-2026
measure: Evaluation of cytokine levels
timeFrame: 2021-2026
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Study officials:
References: