Measurement of apoptosis and proliferation of bone marrow plasma cells in patients with plasma cell proliferative disorders

The proliferative rate of malignant plasma cells, as measured by the plasma cell labelling index (PCLI), is an important prognostic factor in multiple myeloma (MM); however, the PCLI alone is probably inadequate to describe t umour growth because it ignores the idea that myeloma cells may have a redu ced rate of apoptosis. The aims of this study were to develop a now cytomet ric method to measure the apoptosis index of fresh marrow plasma cells and develop a plasma cell growth index (PCGI) that related both proliferation a nd apoptosis to disease activity, Marrow aspirates were obtained from 91 pa tients with plasma cell disorders and the plasma cells in apoptosis were id entified by either 7-amino actinomycin-D (7-AAD) or annexin V-FITC three-co lour flow cytometry, The median plasma cell apoptotic index (PCAI) for pati ents with monoclonal gammopathy of undetermined significance (MGUS), smould ering or indolent myeloma (SMM/IMM), and new multiple myeloma (MM) was 5.2, 3.4 and 2.4, respectively (P=0.03, MGUS v MM). The median PCLI for these s ame patient groups was 0.0, 0.2 and 0.6, respectively (P<0.001, MGUS v MM). The paired PCLI and PCAI for each sample were used to derive the PCGI=2+[P CLI - (0.1)(PCAI)]. The median PCGI for patients with inactive disease (MGU S, SMM/IMM or amyloidosis) was 1.8 compared to 2.4 for those with active di sease (new or relapsed MM) (P<0.001). These results suggest that a decrease in the PCAI may be a factor in the progression from MGUS to SMM to overt M M.