No generally accepted staging system exists for monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of bone, or extramedullary plasmacytoma. Of the plasma cell neoplasms, a staging system exists only for multiple myeloma.
Multiple myeloma is staged by estimating the myeloma tumor cell mass on the basis of the amount of monoclonal (or myeloma) protein (M protein) in the serum and/or urine, along with various clinical parameters, such as hemoglobin and serum calcium concentrations, the number of lytic bone lesions, and the presence or absence of renal failure. Impaired renal function worsens prognosis regardless of stage.
The stage of the disease at presentation is a strong determinant of survival, but it has little influence on the choice of therapy since almost all patients, except for rare patients with solitary bone tumors or extramedullary plasmacytomas, have generalized disease.
International staging system
The International Myeloma Working Group studied 11,171 patients, of whom 2,901 received high-dose therapy and 8,270 received only standard-dose therapy.
An International Staging System was derived and is shown below in Table 2 2.
Table 2. 2. The International Staging System for Multiple Myeloma
|Stage||Criteria||Median Survival (mo)|
|I||Beta-2-microglobulin <3.5 mg/L and albumin ≥3.5 g/dL||62|
|II||Beta-2-microglobulin <3.5 mg/L and albumin <3.5 g/dL or beta-2-microglobulin 3.5 mg/L to <5.5 mg/L||44|
|III||Beta-2-microglobulin ≥5.5 mg/L||29|
Genetic factors and risk groups
Genetic aberrations detected by interphase fluorescence in situ hybridization (FISH) may define prognostic groups in retrospective and prospective analyses.[2,3] Short survival and shorter duration of response to therapy have been reported with t(4;14)(p16;q32), t(14; 16)(q32;q23), cytogenetic deletion of 13q-14, and deletion of 17p13 (p53 locus).[2,3,4,5,6] The question of whether the choice of therapy based on FISH analysis can influence outcome must await further study in prospective trials.
Newer clinical investigations are stratifying patients with multiple myeloma into a so-called standard-risk group, which accounts for 75% of patients and has a median survival of 3 to 6 years, and a high-risk group, which has a median survival of less than 3 years.[2,3,4,5,6,7] (See Table 3 3 below.) This stratification, based on cytogenetic findings, has been derived from retrospective analyses and requires prospective validation. Bone marrow samples are sent for cytogenetic and FISH analysis. Plasma cell leukemia has a particularly poor prognosis.