Plasma cell dyscrasias are a group of diseases with malignant proliferation of a monoclonal population of plasma cells. These cells may or may not secrete detectable levels of the monoclonal immunoglobulin or paraprotein commonly referred to as M protein. Although the most common plasma cell dyscrasia is monoclonal gammopathy of undetermined significance (MGUS), closely related disorders include multiple myeloma, solitary plasmacytoma of bone, extramedullary plasmacytoma, Waldenström macroglobulinemia (WM), primary amyloidosis, and heavy-chain disease. The spectrum of MGUS, solitary plasmacytoma of bone, and asymptomatic and symptomatic multiple myeloma may actually represent a natural progression of the same disease. This chapter focuses on the etiology, diagnosis, clinical features, and current therapy for multiple myeloma and other plasma cell disorders.
Since the publication of the first edition in 2006, there has been much progress in our understanding of the biology of multiple myeloma (MM) and in its treatments. New diagnostic criteria have been developed, and an International Staging System has replaced the Durie-Salmon Staging System. The role of single and double autologous stem cell transplantation has been clarified by randomized trials. Most importantly, thalidomide, bortezomib, lenalidomide, and liposomal doxorubicin have emerged as new active agents and are rapidly being incorporated into the treatment of both newly-diagnosed and relapsed MM.
Multiple myeloma (MM) is a malignant proliferation of monoclonal plasma cells that produces a monoclonal immunoglobulin. The immunoglobulin secreted in the majority of cases is IgG (60%). Immunoglobulin A (IgA) is secreted in 20%, IgD in 2%, and IgE in <0.1%; biclonal secretion (<1%) is rare. Secretion of light chain only is noted in 18%, and <5% of patients do not secrete an M protein (nonsecretory MM) (1).
The National Cancer Institute estimates that 20,580 people will be diagnosed with multiple myeloma in the United States in 2009, and there will be 10,580 deaths from the disease (2). The median age of diagnosis is 70 years. The incidence is highest in the age range of 75 to 84 years (27.6%), followed by the 65 to 74 year-old range (26.5%). The annual age-adjusted incidence of the disease per 100,000 populations is 6.6 among white men and 4.1 in white women. Among African Americans, the frequency doubles to 14.3 in men and 10.0 in women. Similarly, there is a difference in mortality by racial group. The annual age-adjusted mortality rate per 100,000 is 4.3 and 2.7 in white men and women, respectively. This rate increases to 8.2 and 5.8 in African- American men and women, respectively (3).
No predisposing events appear to be important in the etiology of MM. Some events that have been suggested include radiation exposure (in radiologists and radium-dial workers); occupational exposure (in agricultural, chemical, metallurgical, rubber plant, pulp, paper workers, and leather tanners); and chemical exposure to benzene, formaldehyde, epichlorohydrin, hair dyes, paint spray, and asbestos; most of these associations have been countered by negative correlations (4).
Initially, it was reported that survivors of the atomic bombing of Hiroshima had a greater risk of developing myeloma, but longer follow-up data now refute any evidence ...