Essential Thrombocythemia, Myeloproliferative Neoplasm, Primary Myelofibrosis, Fibrotic Stage, Primary Myelofibrosis, Prefibrotic Stage
Conditions
Keywords
CALR, Myeloproliferative Neoplasm, Essential Thrombocythemia, Primary Myelofibrosis, Thrombocytosis
Brief summary
Prospective study to evaluate the relevance of CALR allele burden monitoring as a molecular marker of disease progression.
Detailed description
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).
Interventions
BIOLOGICALCALR allele burden quantification
* 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
Sponsors
University Hospital, Angers
Ligue contre le cancer, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 3 years follow-up | 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. |
Secondary
| Measure | 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 |
Countries
France
Contacts
CONTACTLaurane COTTIN, Doctor
CONTACTEmma BLANCHET
Outcome results
None listed