Waldenström's Macroglobulinemia

(Primary Macroglobulinemia)

A neoplastic disorder in which there is a proliferation of B cells that produce an M protein of the IgM class.

Waldenström's macroglobulinemia is an uncommon disease with an incidence of about one tenth that of multiple myeloma.

Etiology and Pathophysiology

The etiology is unknown, but the etiologic associations are similar to those of multiple myeloma.

Lymphocytic infiltration of the bone marrow crowds out the normal hematologic elements, producing cytopenic complications, such as anemia. Abnormal B cells produce large amounts of IgM proteins. The manifestations of the illness frequently result from high plasma viscosity resulting from increased levels of these IgM proteins in the plasma.

Symptoms and Signs

Plasma hyperviscosity leads to visual changes, CNS symptoms, heart failure, acute myocardial infarction, and strokes. Infections, bleeding, and anemia (eg, with resulting pallor, weakness, vertigo) are a consequence of lymphocytic infiltration of the bone marrow. Bone pain and lytic lesions are not common. Lymphadenopathy and hepatosplenomegaly are common. Retinal hemorrhages and vascular segmentation in the retinal vessels (sausage links) are characteristic. A history of cold sensitivity or Raynaud's phenomenon may be associated with a cryoglobulin or a cold agglutinin. The course of the illness is similar to that of a low-grade B-cell lymphoma with bone marrow involvement.

Diagnosis

Waldenström's macroglobulinemia is diagnosed when there is both a B-cell lymphocyte proliferation and an overproduction of a monoclonal IgM. In contrast to multiple myeloma, there is no plasma cell proliferation and no bone destruction.

The serum protein electrophoresis shows a sharp protein peak, with gamma motility. Serum immunoelectrophoresis demonstrates that the M protein is an IgM. Urine immunoelectrophoresis frequently reveals a monoclonal light chain (usually k), but gross Bence Jones proteinuria is rare. Osteolytic lesions are not usually found. The bone marrow shows a variable increase in lymphocytes and plasmacytoid lymphocytes. Lymph node biopsy usually resembles a diffuse well-differentiated B-cell lymphoma. Serum viscosity commonly is elevated and must be treated.

Other laboratory findings include moderate anemia, high ESR, and rouleaux formation of RBCs on peripheral blood smear. Leukopenia, relative lymphocytosis, and thrombocytopenia occasionally occur. Cryoglobulins, rheumatoid factor, and cold agglutinins may be present. A variety of platelet and coagulation abnormalities may be found.

Prognosis and Treatment

The prognosis is variable, but the course tends to be much more benign than in multiple myeloma. When hyperviscosity is controlled, the course seems to be similar to that of CLL. Hyperviscosity is treated by plasmapheresis. Daily plasma exchanges of 3 to 4 L are recommended until the patient is asymptomatic.

Chemotherapy is reserved for patients who have symptoms due to lymphomatous spread. Chlorambucil is the mainstay of chemotherapy; the regimens are identical to those used in CLL. Fludarabine is sometimes effective for patients refractory to chlorambucil. Regimens identical to those used to treat multiple myeloma have also been used.