This disorder also involves a proliferation of neoplastic B cells, which produce an M protein of the IgM class. The disease is similar to other lymphocytic malignancies, with a median age of approximately 63 years. It is an uncommon disease, with an incidence of approximately one-tenth that of myeloma.

Clinically, the manifestations of the disease are frequently the result of the very high viscosity resulting from an increased level of IgM in the plasma. Visual changes, neurologic symptoms, congestive heart failure, and recurrent infections frequently occur. Bone pain and lytic lesions are rare in macroglobulinemia. Hepatosplenomegaly and lymphadenopathy are common. Retinal hemorrhaging and vascular segmentation (sausage links) are characteristic. A chronic demyelinating polyneuropathy can be seen in 10% of the patients.

The serum protein electrophoresis demonstrates a protein peak of gamma mobility (IgM), and frequently a monoclonal light chain is present in the urine. The bone marrow demonstrates extensive infiltration with so-called plasmacytoid lymphocytes. In one series, the measured serum viscosity related well with development of symptoms; six of eight patients with a serum viscosity higher than 5 cp (normal is 1.8 or lower) had symptoms, whereas no patients had symptoms if viscosity was below 3 cp.

The prognosis for patients with Waldenstrom’s macroglobulinemia can be quite variable. About one-third of patients will die of unrelated causes and one-third will die of infectious complications. The remainder will die of complications of their illness including the conversion to a higher-grade lymphoma, conversion to AML, renal failure, or other complications.

Treatment
Treatment for complications of the M protein, including hyperviscosity, cryoglobulin, or peripheral neuropathy, should be a course of plasmapheresis. The emergent treatment of symptomatic hyperviscosity is effected with plasmapheresis. It is recommended that daily plasma exchanges of 3 to 4 L occur until the patient is asymptomatic.

Reducing further M protein excretion by the lymphocytic clone requires cytotoxic chemotherapy. Chlorambucil is the most frequently used alkylating agent for Waldenstrom’s macroglobulinemia. However, regimens similar to those used for myeloma are also successful. Recently, nucleoside analogues 2-CDA and fludarabine have produced a significant number of responses for untreated patients (80% response rate), as well as those patients refractory to standard alkylating agent therapy.