Clonal Hematopoiesis of Immunological Significance

Immuno-inflammatory Manifestations With or Without Clonal Hematopoiesis: Ambispective Cohort Study

Ambispective, national, multicenter observational cohort study aimed at characterizing the satellite dysimmune manifestations of clonal hematopoiesis, including Vexas (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome.

The clinical spectrum of dysimmune manifestations associated with blood diseases is wide. The pathophysiology of these manifestations is not well understood and their management is poorly codified. This observational cohort aims to list the different clinical pictures, the therapeutic management and the prognosis of patients according to the type of dysimmune manifestations and the type of hemopathy. We wish to have an inventory of the demographic, genetic, clinical and evolutionary data of patients with an inflammatory manifestation associated or not with a myeloid or lymphoid hemopathy. This will make it possible to establish quantitative data on the morbidity and mortality of these rare diseases and to propose therapeutic trials for the most serious patients.

This is an International, multicentre, observational cohort study with retrospective and prospective components (ambispective).

The primary objective is to describe the incidence of immuno-inflammatory manifestations in patients with clonal hematopoiesis or a haematological disease.

The secondary objectives are as follows:

• To describe the clinical and biological presentation of immuno-inflammatory manifestations according to the type of underlying haematological disease or clonal hematopoiesis;
• To describe the clinical and biological presentation of VEXAS syndrome and its association with other haematological diseases;
• To study the relationship between giant cell arteritis and clonal hematopoiesis;
• To specify clinical symptoms according to the genetic mutations identified;
• To define the main genetic mutations associated with these manifestations;
• To identify patients eligible for different therapeutic trials;
• To assess the characteristics of associated haematological diseases;
• To compare the effectiveness of immunomodulatory and antitumour treatments according to the type of immuno-inflammatory manifestation and type of underlying haematological disease or clonal hematopoiesis;
• To study the profile of patients eligible for stem cell transplantation;
• To study mortality in patients followed for an inflammatory disease with or without haematological disease/clonal hematopoiesis;
• To explore the natural history of patients over a 10-year follow-up in order to better characterise long-term complications;
• To build a multicentre reference database enabling cross-sectional and longitudinal analyses to guide future therapeutic strategies;
• To establish correlations between clinical, biological and molecular characteristics in order to better stratify risk and adapt patient management.

Inclusion Criteria:

• Age >=18 years old;
• Confirmed dysimmune manifestations: clinical or biological abnormality or systemic disease;
• Presence or absence of myeloid or lymphoid blood disease according to World Health Organization (WHO) classification

Exclusion Criteria:

• Persons benefiting from special protection: adults under guardianship and curatorship;
• People hospitalized without their consent and not protected by law; persons deprived of liberty;
• Persons not affiliated to the social security system