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Waldenström macroglobulinemia (WM) is a clonal lymphocytic neoplasm resulting in the accumulation, predominantly in the marrow, of immunoglobulin (Ig) M-secreting lymphoplasmacytic cells. Twenty percent of patients have a familial predisposition, indicating an important genetic component. The disease can have long periods of indolence and asymptomatic patients should be followed periodically. Patients with a disease-related hemoglobin level <10g/L, platelet count <100 × 109/L, bulky adenopathy or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or evidence of disease progression should be considered for therapy. Nucleoside analogues and oral alkylating agents should be avoided in younger patients as a result of an increased risk of secondary malignancies, especially myelodysplasia or acute myelogenous leukemia. Plasmapheresis is useful for symptomatic hyperviscosity, and as a prophylactic measure prior to rituximab administration in patients with high plasma IgM levels. Cyclophosphamide in combination with glucocorticoids and rituximab is appropriate initial treatment. Bortezomib in combination with glucocorticoids and rituximab may be particularly beneficial in those patients with symptomatic hyperviscosity and those needing more immediate disease control.

In relapsed or refractory patients, one can use or reuse a frontline regimen or use bortezomib, alemtuzumab, or autologous stem cell transplantation. In a younger patient with a matched donor, allogeneic stem cell transplantation can be considered.

Acronyms and Abbreviations

Acronyms and abbreviations used in this chapter include: CD16, FcγRIIIA receptor; CD40L, CD40 ligand; CDR, complement determination region; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; GM1, ganglioside M1; HCV, hepatitis C virus; Ig, immunoglobulin; IL, interleukin; κ, kappa light chain; λ, lambda light chain; LPL, lymphoplasmacytic lymphoma; MAG, myelin-associated glycoprotein; R-CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab; R-CP, cyclophosphamide, prednisone, rituximab; R-CVP, cyclophosphamide, vincristine, prednisone, rituximab; sCD27, soluble CD27; WM, Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a lymphoid neoplasm resulting from the accumulation, predominantly in the marrow, of a clonal population of lymphocytes, lymphoplasmacytic cells, and plasma cells, which secrete a monoclonal immunoglobulin (Ig) M.1 WM corresponds to lymphoplasmacytic lymphoma (LPL) as defined in the Revised European-American Lymphoma (REAL) and World Health Organization classification systems.2,3 Most cases of LPL are WM; less than 5 percent of cases are IgA-secreting, IgG-secreting, or nonsecreting LPL.

In 1944, Jan Waldenström, a Swedish physician-scientist, reported in Acta Medica Scandinavica three cases of a disease he presciently thought was related to myeloma but for the absence of bone involvement and the scarcity of plasma cells in the infiltrate of small lymphocytes. He noted the increase in plasma protein concentration, marked increased serum viscosity, exaggerated bleeding and retinal hemorrhages, and virtually every other feature of the disorder in his case descriptions. In collaboration with a colleague, he showed, using ultracentrifugation and electrophoresis, that the abundant abnormal protein had a molecular weight of approximately 1 million and was not an aggregate of smaller proteins. The disease, which he described with such thoroughness, was later named in his honor.

The age-adjusted incidence ...

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