This patient should begin combination rituximab plus chemotherapy. He has symptomatic Waldenström macroglobulinemia, demonstrated by a neoplastic infiltrate consisting of clonal lymphocytes, plasmacytoid lymphocytes, plasma cells, and immunoblasts comprising 10% or more of the bone marrow cellularity with disease-related manifestations, including night sweats, weight loss, anemia, lymphadenopathy, and splenomegaly. Management of this low-grade, mature B-cell, non-Hodgkin lymphoma consists of the anti-CD20 monoclonal antibody, rituximab, as single agent therapy or combined with chemotherapy. Considering this patient's degree of symptoms and tumor burden, along with his otherwise good health, combined rituximab and chemotherapy would be highly appropriate. The chemotherapy regimen may consist of an alkylating agent base (such as cyclophosphamide) or purine analog base (such as fludarabine).

Management of anemia should be directed at treating the underlying cause, in this case the Waldenström macroglobulinemia. Plasma exchange is essential for patients presenting with symptomatic hyperviscosity and is occasionally used as adjunctive therapy for cold agglutinin disease, an autoimmune hemolytic anemia that can be associated with Waldenström macroglobulinemia. However, it would not be appropriate in this patient, who does not have symptoms of hyperviscosity. Although the patient is anemic and has an elevated lactate dehydrogenase level, the reticulocyte count is low considering the degree of anemia, no erythrocyte clumps appear on the peripheral blood smear, and the direct antiglobulin (Coombs) test is negative, making a diagnosis of cold agglutinin disease highly unlikely. Furthermore, the patient does not have any clinical manifestations of this disorder (such as acrocyanosis), so a cold agglutinin titer would not be appropriate.

The patient has no symptoms of hyperviscosity (blurry vision, headache, hearing loss, tinnitus, vertigo, dizziness, altered mental status) or findings on physical examination to suggest hyperviscosity (dilated, tortuous retinal veins on funduscopic examination). In the absence of signs and symptoms of hyperviscosity and an M protein of less than 4 g/dL, serum viscosity testing is of no significant value.