There is a group of patients who are suspected as having early or incipient myeloma with a low serum concentration of monoclonal immunoglobulin (the paraprotein), whose bone marrow contains less than 10% of plasma cells and whose skeletal survey shows no bone lesions; such patients do not qualify for the diagnosis of myeloma but are referred to as ‘monoclonal gammopathy of uncertain significance’ (or MGUS).
These patients and those with bone marrow infiltration of 10-30% of plasma cells (also called ‘smouldering myeloma’), as well as all the ‘solitary plasmacytoma’ patients must be kept under careful observation as multiple myeloma may well develop in the future in all these categories.
In patients who ‘qualify’ as suffering multiple myeloma, the prognosis depends on several other factors: patients who present with anaemia, kidney failure, a bone marrow with a very high infiltrate of plasma cells (or worse a plasma cell leukaemia on the peripheral blood film) and/or those with a very high serum paraprotein level, all have a worse outlook for survival than those who do not demonstrate these characteristics on presentation. The foregoing relates to the time honoured Salmon staging system, which concentrated on these clinical features to give a forecast/prognosis as to how any patient is likely to fare.
More recently, other factors that can be ascertained at the time of diagnosis have been demonstrated to impact on the prognosis. For example, a high serum level of beta-2-microglobulin is an independent marker of a poor prognosis. Anaemia (as mentioned above), high blood calcium and low serum level of albumin are also of poor prognostic influence. Atypical plasma cell appearances in the bone marrow (e.g. in terms of mitotic activity) are poorly prognostic.
Further, cytogenetic abnormalities (structural genetic abnormalities detectable in the genes of the malignant plasma cells) have been shown to be prognostic e.g. gene expression profiling is likely in the future to further refine the classification of myeloma in terms of prognostic impact.