Treatment options in Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is a rare chronic B-cell lymphoproliferative disorder characterized by macroglobulin (immunoglobulin M; IgM) paraproteinemia. The clinical manifestations associated with WM can be related to those of direct organ tumor infiltration, hyperviscosity and tissue deposition of IgM. Treatment must be individualized according to the nature of the clinical manifestations. Plasmapheresis has a role in patients whose symptoms are caused by increased serum viscosity. Chlorambucil was first used with response rates varying between 31% and 72% and is now probably the most commonly used oral agent. Melphalan and cyclophosphamide may have similar clinical efficacy. The addition of corticosteroids does not seem to increase response rates and the use of combination chemotherapy in the first-line setting is not recommended. Fludarabine and cladribine are cross-resistant and induce a response in 30%-60% of patients who have had prior therapy with alkylating agents and as many as 100% of previously untreated patients. Thirty-five percent to 50% of patients respond to single rituximab therapy, with limited toxicity. There are no data from prospective randomized studies to guide the choice between alkylating agents, nucleoside analogues, and rituximab for first-line therapy of WM. Autologous and allogeneic stem cell transplantation may be considered for patients with primary refractory/relapsing disease, especially in the younger age groups. Thalidomide alone or in combination with steroids/clarithromycin may be a useful salvage regimen for some heavily pretreated patients with cytopenia, even though toxicity is considerable. Splenectomy is rarely indicated.