Macroglobulinemia
Last reviewed: 23.04.2024
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Macroglobulinemia (primary macroglobulinemia, Waldenstrom's macroglobulinemia) is a malignant plasma-cell disease in which B cells produce large amounts of monoclonal IgM. Manifestations of the disease include increased blood viscosity, bleeding, recurrent infections and generalized adenopathy. For the diagnosis is necessary to study the bone marrow and the definition of M-protein. Treatment includes plasmapheresis with hyperviscosity and systemic therapy with alkylating drugs, glucocorticoids, nucleoside analogues or rituximab.
Macroglobulinemia is clinically more similar to a lymphoproliferative disease than with myeloma and other plasma-cell diseases. The cause of the disease is unknown. Men are sick more often than women. The median age is 65 years.
Macroglobulinemia develops in 12% of patients with monoclonal gammapathy. A large number of monoclonal IgM can be produced in other diseases, causing manifestations similar to macroglobulinemia. A small amount of monoclonal IgM is present in serum in 5% of patients with B-cell non-Hodgkin's lymphoma, in these cases it is called macroglobubinemic lymphoma. In addition, monoclonal IgM is sometimes detected in patients with chronic lymphocytic leukemia or other lymphoproliferative diseases.
Many clinical manifestations of macroglobulinemia are caused by a large amount of high-molecular monoclonal IgM circulating in the plasma. Some of these proteins are antibodies to autologous IgG (rheumatoid factor) or I antigens (cold agglutinins), about 10% are cryoglobulins. Secondary amyloidosis occurs in 5% of patients.
[Symptoms of Macroglobulinemia
In most patients, the disease is asymptomatic, but in many patients there are manifestations of hyperviscosity syndrome: weakness, fatigue, bleeding of mucous membranes and skin, visual impairment, headache, symptoms of peripheral neuropathy and other neurological disorders. An increased volume of plasma can contribute to the development of heart failure. There are cold sensitivity, the phenomenon of Raynaud and recurrent bacterial infections. On examination, generalized lymphadenopathy, hepatosplenomegaly and purpura can be detected. Stagnant, narrowed veins of the retina are characteristic of hyperviscosity syndrome. In the late stages of the retina, hemorrhages, exudate, microaneurysms and papilledema of the optic nerve are determined.
Diagnosis of macroglobulinemia
Suspicion of macroglobulinemia is possible in patients with symptoms of hyperviscosity or other typical manifestations, especially in the presence of anemia. However, the disease is often diagnosed accidentally, when protein electrophoresis reveals M-protein and when immunofiksatsii prove its belonging to IgM. The laboratory examination includes a set of tests for determination of plasma cell diseases, as well as determination of cryoglobulins, rheumatoid factor, Cold agglutinins, coagulation tests and direct Coombs test.
Typical manifestations are moderate normocytic, normochromic anemia, marked agglutination and very high ESR. Sometimes there is leukopenia, relative lymphocytosis and thrombocytopenia. Cryoglobulins, rheumatoid factor or cold agglutinins may be present. In the presence of cold agglutination, the direct Coombs test is usually positive. There may be a variety of coagulation and platelet functional disorders. In the presence of cryoglobulinemia or severe hyperviscosity routine blood tests can give false results. The level of normal immunoglobulins is reduced in half of patients.
Electrophoresis with immunofixation of the urine concentrate often demonstrates the presence of monoclonal light chains (usually k), but there is usually no pronounced Bens-Jones proteinuria. When studying the bone marrow, an increase in the content of plasma cells of various degrees, lymphocytes, plasmacytoid lymphocytes and mast cells is revealed. Periodically, PAS-positive material is detected in lymphoid cells. Lymph node biopsy is performed in a normal bone marrow picture and often shows a picture of diffuse, well differentiated or lymphoplasmocytic lymphoma. The viscosity of the serum is determined to confirm hyperviscosity, which is usually greater than 4.0 (norm 1.4-1.8).
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Treatment of macroglobulinemia
Often, treatment of macroglobulinemia is not required for many years. In the presence of hyperviscosity, treatment begins with plasmapheresis, which quickly eliminates coagulation disorders and neurologic disorders. The courses of plasmapheresis often need to be repeated.
Long-term therapy with oral alkylating agents is indicated for the purpose of reducing symptoms, but it may be accompanied by myelotoxicity. Nucleoside analogues (fludarabine and 2-chlorodeoxyadenosine) cause response in most newly diagnosed patients. The use of rituximab can reduce the tumor mass without suppressing normal hematopoiesis.
Prognosis for macroglobulinemia
The course of the disease is variable with a median survival of 7 to 10 years. Age over 60 years, anemia, cryoglobulinemia worsen the prognosis for survival.