Novel Options of Therapy in Waldenstro¨m Macroglobulinemia

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, U.S.A.Anne-Sophie Moreau and Xavier LeleuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, U.S.A. and Service des Maladies du Sang,CHRU, Lille, FranceMeletios A. DimopoulosDepartment of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, GreeceINTRODUCTIONWaldenstro¨m macroglobulinemia (WM) is a distinct low grade B-cell lymphoma characterized by the presence of lymphoplasmacytic cells in bone marrow and a serum monoclonal IgM protein (1-3). It was first described by Dr. Jan Gosta Waldenstro¨m in 1944 when he identified two patients who developed oronasal bleeding, lymphadenopathy, anemia, and thrombocytopenia, elevated erythrocyte sedimentation rate, high serum viscosity, normal bone radiographs, and bone marrow showing predominantly lymphoid cells (3,4). The overall incidence of WM is about three per million persons per year, with 1500 new cases diagnosed per year in the United States (5,6). Unlike multiple myeloma, WM is more common in Caucasians than in African Americans (5). It is a sporadic disease with unknown etiology; however, studies have demonstrated a high familial incidence of this disease, with 18.7% of the patients having at least a first degree relative with a B-cell neoplasm (7,8). The main risk factor for the development ofWM is the presence of IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS) (9), which confers a 46-fold higher relative risk to develop WM than the general population (9). The median overall survival of patients with WM is 5-6 years; however a recent study in 337 patients with symptomatic WM, demonstrated median disease-specific survival of 11.2 years (10).