1.1 Definitions
1.1.1 Multiple myeloma
Multiple myeloma is a plasma cell neoplasm characterized by the proliferation of monoclonal plasma cells in the bone marrow, associated with the synthesis of a monoclonal protein, either complete or incomplete (light chains only) and with a high incidence of osteolytic bone lesions.
1.1.2 Indolent (or asymptomatic) multiple myeloma
Multiple myeloma diagnosed by chance in the absence of symptoms, usually after screening laboratory studies.
1.1.3 Smoldering multiple myeloma
Despite criteria compatible with the diagnosis of multiple myeloma, no evidence of progressive course. These are cases with a slow progression, the tumor cell mass is low at diagnosis and the percentage of bone marrow plasma cells in S phase is low (<0,5%).
1.1.4 Solitary myeloma of bone
A single bone lesion, with monoclonal plasma cell infiltrate in the absence of other bone lesions elsewhere on skeletal survey and of bone marrow plasmacytosis.
1.1.5 Extramedullary plasmacytoma
Monoclonal plasma cell infiltrate of tissues other than bone (soft tissues, Waldeyer's ring, gastro-intestinal tract) in the absence of bone lesions on skeletal survey and of bone marrow plasmacytosis.
1.1.6 Macroglobulinemia (Waldenström's macroglobulinemia)
B-cell chronic lymphoproliferative disorder characterized by bone marrow infiltration with monoclonal B cells (with pleomorphic morphologic appearance ranging from small lymphoid cells to mature plasma cells) and by the presence of a serum monoclonal IgM.
1.1.7 Heavy-chain disease
B-cell chronic lymphoproliferative disorder in which a fragment of an Ig heavy chain is secreted by the tumor cells and detected in the serum or in the urine (according to the heavy chain fragment, g-heavy-chain disease, a-heavy-chain disease, m-heavy-chain disease, or d-heavy-chain disease).
1.1.8 Monoclonal Gammopathy of Unknown Significance (MGUS)
Presence in the serum of a monoclonal immunoglobulin detected by screening laboratory studies (usually without urinary light chain, i.e. without Bence-Jones proteinuria) in the absence of symptoms and of abnormalities related to a chronic lymphoproliferative disorder or to a plasma cell neoplasm. The diagnosis of MGUS requires a careful evaluation of diagnostic criteria used for the diagnosis of multiple myeloma and there is an overlap in presenting findings between some patients with MGUS and some patients with indolent multiple myeloma. Overall, each year 1-2of patients with MGUS will progress to a diagnosis of B cell neoplasm.
1.2 Incidence
1.2.1 Multiple myeloma
In northern America, multiple myeloma accounts for 1.1% of all malignancies in whites and 2.1% in blacks, with an average annual incidence in 3-4/100 000 in whites, 6-10/100 000 in blacks. In Europe, incidence figures are similar to those observed in the American white population and have been estimated at 2.6/100 000 in England and 3.3/100 000 in Sweden.
The disease is slightly more common in males. The incidence of multiple myeloma increases with age.
Fewer than 2% of patients are under 40 years at diagnosis. The median age at onset is between 63 and 71 years, according to the series.
Indolent or asymptomatic multiple myeloma accounts for approximately 20% of diagnosed cases and solitary bone myeloma for 3% of cases.
1.2.2 Waldenström's macroglobulinemia
Waldenström's macroglobulinemia is less frequent than multiple myeloma and the annual incidence is less than 1/100 000. The disease is more frequent in older persons (median age 63 years).
1.2.3 MGUS
The incidence of MGUS increases with age. In a large study of 6995 asymptomatic adults over the age of 25, the overall incidence of MGUS was 1% but increased with age up to 3% after age 70 almost 6% in the ninth decade. Subclass distribution includes approximately 75% IgG (mostly IgG1), 10% IgA, 14% IgM. Two thirds have k light chain. Two to three percent of cases may manifest biclonal M protein. The use of more sensitive screening tests such as agarose gel electrophoresis, immunofixation or immunoisoelectric focusing could increase the frequency with which MGUS can be detected.
1.3 Risk factors
1.3.1 Multiple myeloma
The role of genetic factors has only been suggested by several lines of evidence: the increased prevalence of the disease in blacks in the US, the higher incidence of myeloma in first-degree relatives of patients, the slightly increased frequency of HLA antigens C4. Environmental or occupational factors have been examined in large studies but no firm conclusion can be drawn, since some associations may have occurred by chance alone. Occupational exposure to petroleum products, asbestosis and radiation exposure have been considered as risks factors for multiple myeloma. Chronic antigenic stimulation has also been suggested as a predisposing factor but conclusive data are lacking.
1.3.2 MGUS
Age is the major known risk factor for developing of MGUS. A serum M-component can be detected in a variety of diseases different from plasma cell neoplasms, especially in other B-cell malignancies including chronic lymphocytic leukemias, cold-agglutinin diseases or B-cell non-Hodgkin lymphomas. M-components are also occasionally seen in non-lymphoid neoplasms such as carcinomas (colon, breast, prostate or other sites), in auto-immune disorders (Sjögren's syndrome, rheumatoid arthritis), and in miscellaneous disorders (papula mucinosis, Gaucher's disease, cirrhosis, sarcoidosis). Transient M-component has also been observed in patients recovering form various infections (viral hepatitis, CMV infection) and after bone marrow transplantation.
1.4 Referral
According to the clinical presentation at diagnosis, patients can be referred to a variety of specialists including hematologists, oncologists, rheumatologists, nephrologists, general practitioners, specialists of internal medicine.
However, since a thorough analysis of biological parameters and a careful staging evaluation are useful to define the prognosis and to tailor the treatment strategy, it is recommended that patients with multiple myeloma be referred to specialized and experienced institutions. In particular, since intensive therapy with autologous (or allogeneic) stem cell transplantation appears to be the most promising way to improve survival in younger patients, patients under the age of 65 should be referred to oncology or hematology centres having facilities and ongoing clinical trials for such treatments.
1.5 Recent Reviews
1.5.1
Salmon SE, Cassidy JRJ on all aspects (1985).
1.5.2
Barlogie B et al on main biological characteristics (1989).
1.5.3
Alexanian R, Dimopoulos D. on general treatment strategy (1994).
1.5.4
Child JA. on general treatment approach (1994).
1.5.5
Dimopoulos M, Alexanian R. on all aspects of the disease (1994).
References
1.I 1.II 1.III 1.IV
Alexanian R, Dimopoulos D. The treatment of multiple myeloma. New Engl J Med 1994;330:484-489.
Barlogie B, Epstein J, Selvanayagam P, Alexanian K. Plasma cell myeloma- New biological insights and advances in therapy. Blood 1989;73:865-79.
Child JA. Evolving strategies for the treatment of myelomatosis. Br J Haematol 1994;88:672-5.
Dimopoulos M, Alexanian R. Waldenström's macroglobulinemia. Blood 1994;83:1452-9.
1.V
Salmon SE, Cassidy JRJ. Plasma cell neoplasms. in: Cancer. Principles and Practice of Oncology. (Eds) De Vita Jr V, Hellman S, Rosenberg SA. 1985, Philadelphia, pp 1853-95.
© European School of Oncology, 1996
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