Waldenstrom's disease is a B-cell neoplasm characterized by the accumulation of lymphoplas-macytic cells (LPCs) in the bone marrow, and more rarely in the lymph nodes and the spleen, which produce a monoclonal immunoglobulin M (IgM) protein. The diagnosis requires the identification of LPCs in the bone marrow, using specific markers in flow cytometry. The MYD88L265P mutation is found in 95% of cases and the CXCR4 mutation in 30-40% of cases. These markers must be sought because they have a diagnostic and prognostic role, and they might become predictive in the future. The clinical presentation is very variable, and includes anomalies related to the bone marrow infiltration of the LPCs (such as anemia), but also anomalies of the physico-chemical and/or immunological activity of the overproduced IgM (hyperviscosity AL amyloidosis, cryoglobulinemia, anti-MAG neuropathies, etc.). Prognostic scores (IPSSWM) now make it possible to understand the prognosis of symptomatic WM requiring appropriate treatment. The therapeutic management depends on many parameters, such as the specific clinical presentation, the speed of evolution and of course the age and comorbidities. Immuno-chemotherapy is often the 1st line treatment (rituximab-cyclophosphamide-dexame-thasone (RCD) or bendamustine-rituximab (BR)) but the role of targeted therapies is becoming preponderant. Bruton tyrosine kinase inhibitors (BTKi) are used today in first relapse. Other therapeutic perspectives will certainly allow us tomorrow to better understand this incurable chronic disease, such as new generations of BTKi, BCL2 inhibitors, anti-CXCR4, bi-specific antibodies, and CAR-T cells.
展开▼
