Cytobiological studies in multiple myeloma.

Abstract

Multiple myeloma (MM) is a heterogeneous disease in which the median survival time varies from a few months to more than 10 years. Clinical, kinetic, and immunological studies reflected such a heterogeneity. In clinical studies beta 2-microglobulin (beta 2-M), which is a well-known prognostic factor, was evaluated as an expression of tumor burden: a linear increase has been observed from stage I to stage III. No clear cutoff was detected between monoclonal gammopathy of undetermined significance (MGUS) and stage I MM. Kinetic studies have been performed by 3[H]thymidine or 5-bromo-2-deoxyuridine incorporation in bone marrow plasma cells. An analysis has been carried out between beta 2-M and the labeling index (LI). No correlation has been observed between these 2 parameters which identify different subgroups of poor prognosis patients. MGUS always showed an LI less than 1% allowing a clear distinction from stage I MM. A reduced survival time has been observed in patients with an LI greater than 2%. A subgroup of MM patients characterized by an LI greater than 2% and a decrease of M component greater than 50% within 3 months (early responders) has been identified. These patients showed a median survival time of about 10 months. Immunological studies identified a sharp decrease of 5' nucleotidase (5'NT) enzymatic activity in peripheral blood lymphocytes. This enzymatic defect is the biochemical marker of the expansion of a T subpopulation expressing low levels of 5'NT. This subpopulation was characterized by monoclonal antibodies and is represented by activated suppressor cells (OKM1+, DR+). Such an unbalancement in the T cell subpopulation was evident in poor prognosis patients. Clinical, kinetic and immunological studies identified new prognostic parameters that will be useful in the future therapeutic strategy of MM.