It is characterized by having high levels of a circulating antibody, immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease.
Because of its indolent nature, many patients are able to lead active lives and, when treatment is required, may experience years of symptom-free remission.
[8] Signs and symptoms of Waldenström macroglobulinemia include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums.
[citation needed] Waldenström macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes.
[12] However, CXCR4 mutation is not associated with splenomegaly, high platelet counts, or different response to therapy, questioning the relevance of CXCR4 in treating patients.
[14] There are genetic factors with first-degree relatives of Waldenström macroglobulinemia patients shown to have a highly increased risk of also developing the disease.
[15] There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of Waldenström macroglobulinemia.
[16] Although believed to be a sporadic disease, studies have shown increased susceptibility within families, indicating a genetic component.
[43] Symptoms including blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effects of the IgM paraprotein, which may cause autoimmune phenomena or cryoglobulinemia.
[48] A diagnosis of Waldenström macroglobulinemia depends on a significant monoclonal IgM spike, which is evident in blood tests and malignant cells consistent with the disease in bone marrow biopsy samples.
[50] Additional tests such as computed tomography (CT or CAT) scan may be used to evaluate the chest, abdomen, and pelvis, particularly swelling of the lymph nodes, liver, and spleen.
A low level of neutrophils (a specific type of white blood cell) may also be found in some individuals with Waldenström macroglobulinemia.
Immunoelectrophoresis and immunofixation studies help identify the type of immunoglobulin, the light chain's clonality, and the paraprotein's monoclonality and quantitation.
High-resolution electrophoresis and serum and urine immunofixation are recommended to help identify and characterize the monoclonal IgM paraprotein.
Results from characterization studies of urinary immunoglobulins indicate that light chains (Bence Jones protein), usually of the kappa type, are found in the urine.
[58][clarification needed] Patients with Waldenström macroglobulinemia are at higher risk of developing second cancers than the general population, but it is not yet clear whether treatments are contributory.
These asymptomatic cases are now classified as two successively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia.
[5][6] But on occasion, the disease can be fatal, as it was to the French president Georges Pompidou, who died in office in 1974, six years after the discovery of his cancer.
[63] Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide.
[74] A database of clinical trials investigating Waldenström macroglobulinemia is maintained by the National Institutes of Health in the U.S..[75] Patients with polymorphic variants (alleles) FCGR3A-48 and -158 were associated with improved categorical responses to rituximab-based treatments.
[78] The International Prognostic Scoring System for Waldenström's Macroglobulinemia is a predictive model to characterise long-term outcomes.
Waldenström macroglobulinemia was first described by Jan G. Waldenström (1906–1996) in 1944 in two patients with bleeding from the nose and mouth, anemia, decreased levels of fibrinogen in the blood (hypofibrinogenemia), swollen lymph nodes, neoplastic plasma cells in bone marrow, and increased viscosity of the blood due to increased levels of a class of heavy proteins called macroglobulins.
[87] For a time, Waldenström macroglobulinemia was considered to be related to multiple myeloma because of the presence of monoclonal gammopathy and infiltration of the bone marrow and other organs by plasmacytoid lymphocytes.