THE BIOLOGICAL AND CLINICAL-SIGNIFICANCE OF THE KI-67 GROWTH FRACTION IN MULTIPLE-MYELOMA

We tested the significance of the Ki-67 plasma cell growth fraction in 49 bone marrow samples from 42 patients with multiple myeloma (MM). As a new approach to study myeloma cell proliferation, strong positivity of the CD38 antigen as plasma cell related feature was simultaneously evaluated with nuclear Ki-67 expression in a flow cytometric double immunofluorescence assay. Mean Ki-67 values were significantly higher in MM at relapse (22.4 per cent +/- 10.4) as compared with MM at diagnosis (11.9 per cent +/- 8.4, p < 0.005) and plateau-phase (10.0 per cent +/- 5.5, p < 0.001), respectively. Serial observations in six patients confirmed this change in cell kinetic behaviour during the course of the disease. Elevated Ki-67 values correlated significantly with stage III (versus stage I, p < 0.05), beta-2-microglobulin serum levels > 6 (p < 0.001), plasmablastic morphology (p < 0.001), and diploid myeloma cell DNA-content (p < 0.005). No correlation was found between Ki-67 and immunoglobulin isotypes as well as immunophenotypic features (expression of CD10, CD33, and CD56) of myeloma cells. Clinically, six of seven patients with Ki-67 > 14 per cent at diagnosis had an unfavourable course (primary resistant disease or early relapse), and three of four patients with elevated Ki-67 values at plateau-phase relapsed within 3 months. Our results demonstrate the usefulness of Ki-67 in determining proliferative activity in MM and emphasize its value in the evaluation of the risk profile of MM patients.