Monoclonal gammopathies: new approaches to clinical problems in diagnosis and prognosis.

When a patient presents with monoclonal gammopathy, a wide variety of clinical conditions must be considered. The importance of distinguishing accurately between patients with stable monoclonal gammopathies and those with overt multiple myeloma cannot be over-emphasised. The bone marrow examination with plasma cell labeling index, and newer techniques such as magnetic resonance imaging and computed tomography can improve diagnostic discrimination. In difficult cases, the detection of small numbers of circulating myeloma cells, the peripheral blood B-cell labeling index, and light chain isotype suppression may bring better diagnostic resolution. These tests may also be used to help assess disease activity. If the diagnosis is multiple myeloma, prediction of outcome assumes clinical importance. There are widely disparate survivals among patients with different clinical presentations. Standard clinical assays or a combination of these as in clinical staging do not provide sufficient prediction of outcome but are routinely available and therefore widely used. Independent predictive tests such as the plasma cell labeling index and beta 2-microglobulin improve prognostic accuracy. Ploidy analysis and immunophenotyping are additional variables that may assume more importance as the results of ongoing studies appear. Other promising approaches include detection of oncogene and multiple drug resistance gene expression. All such techniques will become more relevant as we apply more intensive treatment earlier in the disease course, particularly for the younger myeloma patients in whom the prognosis is poor.