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 tumour growth because it ignores the idea that myeloma cells may have a reduced rate of apoptosis. The aims of this study were to develop a flow cytometric method to measure the apoptosis index of fresh marrow plasma cells and develop a plasma cell growth index (PCGI) that related both proliferation and apoptosis to disease activity. Marrow aspirates were obtained from 91 patients with plasma cell disorders and the plasma cells in apoptosis were identified by either 7-amino actinomycin-D (7-AAD) or annexin V-FITC three-colour flow cytometry. The median plasma cell apoptotic index (PCAI) for patients with monoclonal gammopathy of undetermined significance (MGUS), smouldering 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 same 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 + [PCLI - (0.1)(PCAI)]. The median PCGI for patients with inactive disease (MGUS, SMM/IMM or amyloidosis) was 1.8 compared to 2.4 for those with active disease (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 MM.