Prognostic significance of plasma cell propidium iodide and annexin-V indices and their mutual ratio in multiple myeloma.

The aim of this study was a contemporaneous measurement of plasma cells proliferative and apoptotic activity in patients examined at the time of multiple myeloma (MM) diagnosis before initiation of chemotherapy, focussed on the following aspects: determination of prognostic significance of plasma cell propidium iodide (PC-PI) and annexin-V FITC (PC-AI) indices; optimal cut off of PC-PI and PC-AI with regard to overall survival; calculation of summary kinetic index of plasma cells (PC-PI/AI ratio) for evaluation of its prognostic importance; determination of an index (out of PC-PI, PC-AI and PC-PI/AI) showing the closest relation to prognosis of multiple myeloma. The analyzed 122 patients fulfilling SWOG multiple myeloma criteria were treated by conventional chemotherapy. Plasma cell proliferative activity was measured by means of PC-PI examined by flow cytometry using a DNA/CD138 double staining technique. For detection of plasma cells entering apoptosis (PC-AI), flow-cytometry method with annexin-V FITC and MoAb CD138 was used. The PC-PI median in 122 patients was 2.6(0.4-4.8)%. The sequence prognostic analysis showed that the optimal PC-PI cut off was 2.9% and displayed a significant relationship with overall survival (OS) (p=0.031). The group of 94 patients had PC-AI median of 5.0(1.4-24.5)%. The best statistical significance of the rate of apoptosis related to overall survival was found at cut off value of 4.4% (p=0.022). The median of overall kinetic index of plasma cells (PC-PI/AI) examined in 94 MM patients was 0.5(0.05-2.60) and the overall kinetic index was found to display a very good relationship to OS at the cut off value of 0.71 (p=0.032). All the three indices expressing various aspects of kinetics of plasma cells allow the stratification of patients into two prognostically different groups with statistically significantly different medians of overall survival: good risk - OS still undeterminable at the time of analysis; bad risk - M: OS was for PC-PI 17 months, for PC-AI 23 months and for PC-PI/AI 16 months. The ratio of both indices, i.e. PC- PI/AI, however did not bring any further contribution to overall survival/prognosis evaluation, when compared with single PC-PI and PC-AI. Results of present study indicates that the evaluation of both proliferation and apoptotic activities of plasma cells is important for prognosis thus extending possibilities of initial stratification of MMpatients into groups with different prognostic risk.