Multiple myeloma: clinical evaluation of plasma cell lymphoproliferative disorders and initial management.

After many years of nosologic errance, plasma cell lymphoproliferative disorders are now firmly classified as belonging to the lymphoma family. Their characteristic biological and clinical course starts from the localized form of plasmacytoma, progressing to the more diffuse benign gammopathy, then the premalignant conditions like indolent (IM) or smouldering (SM) myeloma, and ending at the multiple myeloma (MM) stage. During and before this multistep development, genetic and environmental factors appear to be involved and spontaneous regressions may even occur. However, when MM is diagnosed, the outcome is invariably fatal despite conventional radiotherapy and chemotherapy. Prognostic factors like G-reactive protein, the plasma cell labeling index, and beta 2-microglobulin are extremely useful not only for determining the aggressivity of the abnormal clone but also for predicting the transformation from a benign state to a definitive malignant condition. Standard single-agent chemotherapy with melphalan and multidrug combinations can significantly prolong survival, but no cure has yet been achieved. High-dose chemotherapy with stem cell support can decrease tumor burden to an undetectable level and, compared with conventional approaches, has recently proved to increase response rates, the symptom-free interval, and survival. Moreover, interferon alfa is also able to prolong the responding interval, but this has yet to be translated into a survival advantage. These new more aggressive therapies are reminiscent of the early days of leukemia treatment and should now be offered to patients in controlled trials on the basis of comorbidities rather than age or some discriminating economic factors.