Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)

Study Overview
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Brief Summary
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Prospective study to evaluate the relevance of CALR allele burden monitoring as a molecular marker of disease progression.

Detailed Description
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A first local study on 45 patients showed the prognostic impact of CALR mutation quantification in follow-up, independently of the European LeukemiaNet (ELN) prognostic score validated in this group of patients. This study aims to evaluate a multicenter cohort of 260 patients, including all types of CALR-mutated MPNs and several follow-up samples, to model the temporal evolution of CALR allele burden. Blood of MPN patients will be collected, at the time of diagnosis and for 3 years (max 1 sample/year), for the quantification of the CALR allele burden. During follow-up, a clinicobiological score to define the progression or not of the disease for each patient will be evaluated in Essential Thrombocythemia (ET) and MyeloFibrosis (MF).

Official Title
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Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)

Conditions
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Myeloproliferative Neoplasm, Essential Thrombocythemia, Primary Myelofibrosis, Prefibrotic Stage, Primary Myelofibrosis, Fibrotic Stage

Intervention / Treatment
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* Biological: CALR allele burden quantification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults (age ≥18 years), affiliated to the national social security system, with CALR mutated myeloproliferative neoplasm diagnosed between 2006 - 2020, for which at least one sample is available at the time of diagnosis or before cytoreductive treatment, who signed the consent to participate in the study, included, or consenting to be included, in the national clinical-biological database of France Intergroupe Syndrome Myéloprolifératifs (FIM). Exclusion Criteria: patient with another active hematological disease or cancer at the time of diagnosis, person subject to legal protection scheme or incapable of giving consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CALRSUIVI cohort<br> | Biological: CALR allele burden quantification<br>* DNA extraction from blood sample for CALR mutation quantification (fragment analysis) at diagnosis and follow-up (inclusion period: 3 years) max 1 sample/year secondary outcome: mutational landscape by Next Generation Sequencing (NGS) analysis at diagnosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For each disease, Hazard Ratio of the different trajectories of CALR allele burden to explain the time to onset of disease progression by the clinicobiological score. | Clinicobiological score : For ET, disease progression if ≥ 1 of: leukocytosis > 12 G/L or myelemia > 10% or erythroblasts > 1%, anemia or thrombocytopenia not related to drug toxicity, development or worsening of splenomegaly, development of thrombocytosis (platelets > 450 G/L) on cytoreductive therapy, poor disease control (at least one change in therapy for reasons other than adverse events), hematologic transformation or death related to hematologic pathology. For MF, disease progression if ≥ 1 of: anemia < 100 g/L, neutropenia < 1 G/L, thrombocytopenia < 100 G/L and/or development of general signs not previously present or recurring after improvement, increase in leukocytosis > 25 G/L not previously present, appearance or aggravation of transfusion dependence, appearance (> 5 cm) or aggravation (> 50%) of splenomegaly, leukemic transformation or death related to the hematologic pathology. | 3 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A multinomial logistic model will be performed to identify the characteristics associated with the different trajectories of CALR allele burden (pathology, treatment, additional mutations, type of CALR mutation). |  | 3 years follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CALR, Myeloproliferative Neoplasm, Essential Thrombocythemia, Primary Myelofibrosis, Thrombocytosis