A NEW STAGING SYSTEM FOR MULTIPLE-MYELOMA BASED ON THE NUMBER OF S-PHASE PLASMA-CELLS

In the present study, we analyzed the cell cycle distribution of bone marrow (BM) cells in 120 untreated multiple myeloma patients using a D NA/CD38 double-staining technique at flow cytometry in which plasma ce lls (PCs) can be clearly discriminated from residual BM cells based on their CD38 expression. This approach allows us to determine the proli ferative activity of both PCs and residual normal BM cells. The percen tage of S-phase cells in the myelomatous population was found to be si gnificantly lower than that of the residual normal BM cells (P < .001) . Regarding the proliferative activity of myelomatous cells, patients with a high number of S-phase PCs (>3%) showed a significantly (P < .0 5) increased incidence of anemia and hypercalcemia; higher values of b eta(2)-microglobulin (beta(2)M), urea, and creatinine; and higher numb ers of peripheral blood natural killer cells, as well as a poor progno sis as assessed both by response duration and overall survival. With r espect to the residual BM normal fraction, a low proliferative activit y was significantly (P < .05) associated with the presence of anemia a nd neutropenia together with increased numbers of BM PCs, a higher inc idence of Bence Jones myelomas, and DNA diploidy. Multivariate analysi s showed that the number of S-phase PCs was the most important indepen dent prognostic factor, allowing us to discriminate two subgroups of p atients with different prognoses, even within the same clinical stage. Moreover, the S-phase PCs, together with beta(2)M, age, and performan ce status, represent the best combination of disease characteristics f or stratifying patients according to prognosis and allow the establish ment of a simple and powerful staging system for multiple myeloma pati ents. In addition, this classification can be used for planning treatm ent in patients who are candidates for transplantation. (C) 1995 by Th e American Society of Hematology.