Waldenstroms macroglobulinemia

Malignancy of lymphoplasmacytoid cells that secreted IgM. In contrast to myeloma, the disease was associated with lymphadenopathy and hepatosplenomegaly, but the major clinical manifestation was hyperviscosity syndrome.

• The disease resembles the related diseases chronic lymphocytic leukemia, myeloma, and lymphocytic lymphoma.
• It originates from a post–germinal center B cell
• Waldenstrom’s macroglobulinemia (WM) and IgM myeloma follow a similar clinical course, but therapeutic options are different.
• Like myeloma, the disease involves the bone marrow, but unlike myeloma, it does not cause bone lesions or hypercalcemia.
• Bone marrow shows >10% infiltration with lymphoplasmacytic cells. Like myeloma, an M component is present in the serum in excess of 30 g/L (3 g/dL), but unlike myeloma, the size of the IgM paraprotein results in little renal excretion, and only 20% of patients excrete light chains. Therefore, renal disease is not common.
• Patients present with weakness, fatigue, and recurrent infections similar to myeloma patients, but epistaxis, visual disturbances, and neurologic symptoms such as peripheral neuropathy, dizziness, headache, and transient paresis are much more common in WM.
• Physical examination reveals adenopathy and hepatosplenomegaly, and ophthalmoscopic examination may reveal vascular segmentation and dilation of the retinal veins characteristic of hyperviscosity states.
• Patients may have a normocytic, normochromic anemia, but rouleaux formation and a positive Coombs’ test are much more common than in myeloma. Malignant lymphocytes are usually present in the peripheral blood.
• About 10% of macroglobulins are cryoglobulins. These are pure M components and are not the mixed cryoglobulins seen in rheumatoid arthritis and other autoimmune diseases. Therefore Raynaud’s phenomenon and serious vascular symptoms precipitated by the cold are occasionaly present.

Treatment

• Control of serious hyperviscosity symptoms such as an altered state of consciousness or paresis can be achieved acutely by plasmapheresis because 80% of the IgM paraprotein is intravascular.
• The median survival of affected individuals is 50 months, similar to that of MM.
• Many patients with WM have indolent disease that does not require therapy.
• Pretreatment parameters including older age, male sex, general symptoms, and cytopenias define a high-risk population.
• Treatment is usually not initiated unless the disease is symptomatic or increasing anemia, hyperviscosity, lymphadenopathy, or hepatosplenomegaly is present.
• Bortezomib and bendamustine are two agents with significant efficacy in WM.
• Rituximab (anti-CD20) can produce responses, alone or combined with either of these two agents. Rituximab can produce IgM flare, so its use is initially withheld in patients with high IgM levels. Fludarabine (25 mg/m2 per day for 5 days every 4 weeks) and cladribine (0.1 mg/kg per day for 7 days every 4 weeks) are also highly effective single agents.
• Although highdose therapy plus autologous transplantation is an option, its use has declined due to the availability of other effective agents.