Blood 83(6): 1452-1459, 1994.
Dimopoulos MA, Alexanian R
Waldenstrom's macroglobulinemia, which represents about 2% of hematologic cancers, and is a low-grade, small-cell lymphoma, is characterized by a monoclonal macroglobulinemia. It occurs mainly among older individuals and exhibits family clustering. Tumor infiltration is most frequent in the bone marrow, lymph nodes and spleen, there is usually anemia, monoclonal blood lymphocytosis and Bence Jones proteinuria. Circulating IgM may be associated with hyperviscosity in essentially all patients with the lymphoma, cryoglobulinemia in about 15%, although fewer than 5% have symptoms, and cold agglutinin anemia in about 10%. Tissue IgM deposition is associated with peripheral neuropathy in about 5-10%, and much less common glomerular disease and amyloidosis. For IgM-induced complications, plasma exchange transfusion should be considered, and may be performed on an automatic blood cell separator using albumin and saline replacement. This produces rapid reduction in IgM which is 80% intravascular, but chemotherapy is required for the lymphoma. Chemotherapy has included chlorambucil and prednisone (57% response rate), cyclophosphamide, vincristine, prednisone, with or without doxorubicin (65% and 44% responses), and nucleoside analogs fludarabine or 2-chlorodeoxyadenosine (79% responses). These nucleoside analogs may provide significant response rates in patients initially resistant to alkylating agent/prednisone combinations (54% responses for a 30 month median survival), but responses have been only about 18% in those becoming resistant to ongoing therapy. Myelodysplasia and acute myelogenous leukemia have occurred in patients treated with alkylating agent combinations. Transformation of the macroglobulinemia to a large-cell lymphoma with reduced IgM levels occurs as a result of natural clonal evolution. Among prognostic factors, age over 60 years, male gender, and hemoglobin below 10 g/dL indicated shorter survival. In survival studies attention should be paid to cause-specific mortality, since 16-23% die of unrelated causes in these primarily older patients. (74 Refs.)
Rheinische Friedrich- Wilhelms- Universität Bonn