Macroglobulinemia

(Primary macroglobulinemia, Waldenstrom macroglobulinemia)

Macroglobulinemia is a malignant plasma cell disease, form excessive amounts of IgM paraprotein in B-cells. The manifestations may include hyperviscosity, bleeding, recurrent infections and a generalized lymphadenopathy. Diagnosis requires a bone marrow examination and detection of paraprotein. The treatment includes a plasma exchange with hyperviscosity as well as systemic therapy with alkylating drugs, corticosteroids, nucleoside analogues and monoclonal antibodies.

Macroglobulinemia, an unusual B-cell tumor, clinically resembles more of a lymphatic disease as myeloma and other plasma cell diseases. Its cause is unknown. Men are affected more frequently than women; the median age is 65 years.

Macroglobulinemia is a malignant plasma cell disease, form excessive amounts of IgM paraprotein in B-cells. The manifestations may include hyperviscosity, bleeding, recurrent infections and a generalized lymphadenopathy. Diagnosis requires a bone marrow examination and detection of paraprotein. The treatment includes a plasma exchange with hyperviscosity as well as systemic therapy with alkylating drugs, corticosteroids, nucleoside analogues and monoclonal antibodies. Macroglobulinemia, an unusual B-cell tumor, clinically resembles more of a lymphatic disease as myeloma and other plasma cell diseases. Its cause is unknown. Men are affected more frequently than women; the median age is 65 years. After myeloma macroglobulinemia is the second most common malignant disease which is associated with of monoclonal gammopathy. Excessive amounts of paraprotein can also accumulate in other diseases and similar trigger the changes macroglobulinemia. Small monoclonal IgM components are found in the serum of about 5% of patients with non-Hodgkin’s B-cell lymphomas. This condition is referred to as makroglobulinämisches lymphoma. In addition, para proteins are found occasionally in patients with chronic lymphocytic leukemia or other lymphoproliferative disorders. Clinical manifestations of macroglobulinemia may be due to the large amount of circulating plasma IgM monoclonal proteins high molecular weight, but most patients with high IgM levels no problems. Some of these proteins are antibodies directed against autologous IgG (rheumatoid factor) or I antigen (cold agglutinins) are directed. About 10% are Cryoglobulins. Secondary amyloidosis occurs in 5% of patients. Symptoms and signs Most patients are asymptomatic, but often there are signs of anemia, and hyperviscosity syndrome: fatigue, weakness, skin and mucosal bleeding, blurred vision, headache, signs of peripheral neuropathy and other neurological manifestations changing. An increased plasma volume can cause heart failure. Furthermore, sensitivity to cold, Raynaud’s syndrome or recurrent bacterial infections can occur. On examination, lymphadenopathy, hepatosplenomegaly and purpura can (which may be the first sign in rare cases) found. Increased blood volume and circumscribed narrowing of retinal veins that resemble the constrictions at sausages, suggest a hyperviscosity syndrome. Retinal hemorrhages, exudates, microaneurysms and papilledema occur in the late stage. Tips and risks Increased congestion and circumscribed narrowing of retinal veins that resemble the constrictions at sausages, suggest a hyperviscosity syndrome. Diagnosis Blubild with platelets, red cell indices and peripheral blood smear Serum protein electrophoresis followed by serum and urine immunofixation and quantitative Immunoglobulinspiegeln study of serum viscosity bone marrow examination Occasionally lymph node biopsy A macroglobulinemia is suspected in patients with symptoms of hyperviscosity or other typical symptoms, especially in the presence of anemia. However, the diagnosis is often happens when a protein electrophoresis showing a paraprotein which proves in immunofixation as IgM. The laboratory tests include tests for evaluation of plasma cell diseases (multiple myeloma, multiple myeloma) and the determination of cryoglobulins, rheumatoid factor and cold agglutinins and coagulation tests and the direct Coombs test. A moderate normocytic, normochromic anemia, severe rouleaux formation and a very high ESR are typical. Leukopenia, relative lymphocytosis and thrombocytopenia are uncommon. Cryoglobulins, rheumatoid factor or cold agglutinins may be present. In cold agglutinins direct Coombs test is usually positive. There may be different coagulation and platelet function disorders, and the results of routine blood tests may be disturbed in the presence of cryoglobulinemia or hyperviscosity pronounced. Normal immunoglobulins are decreased in half of the patients. The immunofixation in concentrated urine often shows a monoclonal light chain (usually kappa [?]), but a significant Bence Jones proteinuria is unusual. Bone marrow tests show a different proliferation of plasma cells, lymphocytes, plasmacytoid lymphocytes, and mast cells. PAS-positive material can be found in lymphoid cells. The processing performed in normal bone marrow finding lymph node biopsy is often interpreted as a diffuse, well-differentiated or lymphoplasmacytic lymphoma. The serum viscosity is measured to confirm the suspected hyperviscosity and is – if available – usually> 4.0 (standard: 1.4-1.8). Treatment plasma exchange (with hyperviscosity) corticosteroids, alkylating drugs, nucleoside analogues, monoclonal antibodies (rituximab) alone or in combination may a proteasome inhibitor (bortezomib or Carfilzomib), an immunomodulator (thalidomide, pomalidomide or lenalidomide), Ibrutinib or Idelalisib The median survival of patient is between 7 and 10 years. Age> 60, anemia and cryoglobulinemia associated with a shorter survival time (1). Often the patients for many years do not require therapy (1). Upon the occurrence of hyperviscosity the initial treatment is a plasma exchange, which fixes bleeding and neurological disorders rapidly. Often, the plasma exchange has to be repeated. Corticosteroids may be effective for the reduction in tumor burden. For palliation treatment with oral alkylating agents may be necessary, but it can bone marrow toxicity may occur. With a large number of newly diagnosed patients a response to treatment with nucleoside analogues (fludarabine, and 2-chloro-deoxyadenosine) can be achieved; Nucleoside analogs have, however, associated with a high risk of myelodysplasia, and myeloid leukemia. Rituximab may reduce the tumor burden without suppression of normal hematopoiesis. But in the first months, the IgM levels can increase, requiring a plasma exchange. The proteasome inhibitors bortezomib or carfilzomib and immunomodulatory agents thalidomide, lenalidomide and pomalidomide are also effective in this cancer. Ibrutinib, a Bruton’s tyrosine kinase inhibitor and idelalisib, a PI3K inhibitor, are also effective in these patients. Treatment Note Oza A, Rajkumar SV. Waldenstrom macroglobulinemia: prognosis and mgmt Blood Cancer J O doi: 10.1038 / bcj.2015.28. The important points macroglobulinemia is a malignant plasma cell disease form excessive amounts of IgM paraprotein in B cells. Most patients are asymptomatic, but often there are signs of anemia, and hyperviscosity syndrome: fatigue, weakness, skin and mucosal bleeding, blurred vision, headache, peripheral neuropathy and other neurological manifestations. A serum protein electrophoresis with subsequent serum and urine immunofixation and quantitative Immunoglobulinspiegeln is performed. Hyperviscosity is treated with a plasma exchange which fixes bleeding and neurological disorders quickly. Corticosteroids, fludarabine, rituximab, Proteason inhibitors (bortezomib and carfilzomib), immunomodulators (thalidomide, lenalidomide and pomalidomide) Ibrutimib or idelalisib can be helpful; alkylating drugs can be used for relief.

Health Life Media Team

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