Scudla V, Ordeltova M, Minarik J, Dusek L, Zemanova M, Bacovsky J
3rd Department of Internal Medicine, University Hospital, Medical Faculty of Palacky University, 775 20 Olomouc, Czech Republic.
Neoplasma. 2006;53(3):213-8.
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.
本研究的目的是在化疗开始前对多发性骨髓瘤（MM）诊断时的患者进行浆细胞增殖和凋亡活性的同期测量，重点关注以下方面：确定浆细胞碘化丙啶（PC-PI）和膜联蛋白-V FITC（PC-AI）指数的预后意义；关于总生存期的PC-PI和PC-AI的最佳临界值；计算浆细胞的综合动力学指数（PC-PI/AI比值）以评估其预后重要性；确定与多发性骨髓瘤预后关系最密切的指数（PC-PI、PC-AI和PC-PI/AI中的一个）。分析的122例符合SWOG多发性骨髓瘤标准的患者接受了传统化疗。采用DNA/CD138双重染色技术通过流式细胞术检测PC-PI来测量浆细胞增殖活性。为检测进入凋亡的浆细胞（PC-AI），使用膜联蛋白-V FITC和单克隆抗体CD138的流式细胞术方法。122例患者的PC-PI中位数为2.6（0.4-4.8）%。序列预后分析表明，PC-PI的最佳临界值为2.9%，与总生存期（OS）显示出显著关系（p=0.031）。94例患者组的PC-AI中位数为5.0（1.4-24.5）%。在临界值为4.4%时发现凋亡率与总生存期的统计学意义最佳（p=0.022）。94例MM患者检测的浆细胞综合动力学指数（PC-PI/AI）中位数为0.5（0.05-2.60），在临界值为0.71时发现综合动力学指数与OS显示出非常好的关系（p=0.032）。表达浆细胞动力学不同方面的所有三个指数都能将患者分为两个预后不同的组，总生存期中位数有统计学显著差异：低风险组——分析时OS仍无法确定；高风险组——对于PC-PI，OS为17个月，对于PC-AI为23个月，对于PC-PI/AI为16个月。然而，与单个PC-PI和PC-AI相比，两个指数的比值即PC-PI/AI对总生存期/预后评估没有进一步贡献。本研究结果表明，评估浆细胞的增殖和凋亡活性对预后很重要，从而扩展了将MM患者初步分层为不同预后风险组的可能性。
