Changes in circulating endothelial progenitor cells predict responses of multiple myeloma patients to treatment with bortezomib and dexamethasone

Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM) patients. We investigated whether circulating endothelial progenitor cells (cEPCs) could be a biomarker for predicting patient response in the first cycle of chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs and stromal cell-derived factor-1α (SDF-1α) in 46 MM patients in the first cycle of treatment with bortezomib and dexamethasone, and investigated clinical relevance based on patient response after four 21-day cycles. The mononuclear cell fraction was analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study population was divided into 3 groups according to the response to chemotherapy: good responders (n=16), common responders (n=12), and non-responders (n=18). There were no significant differences among these groups at baseline day 1 (P>0.05). cEPC levels decreased slightly at day 21 (8.2±3.3 cEPCs/μL) vs day 1 (8.4±2.9 cEPCs/μL) in good responders (P>0.05). In contrast, cEPC levels increased significantly in the other two groups (P<0.05). SDF-1α changes were closely related to changes in cEPCs. These findings indicate that change in cEPCs at day 21 in the first cycle might be considered a noninvasive biomarker for predicting a later response, and extent of change could help decide whether to continue this costly chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for improved response and outcomes in MM patients.

需完成4个周期化疗方可评估多发性骨髓瘤（MM）患者的治疗应答情况。本研究旨在探讨循环内皮祖细胞（cEPCs）能否作为硼替佐米联合地塞米松化疗第一周期的患者应答预测生物标志物，从而使患者避免无效且昂贵的治疗，并减少不必要的不良反应暴露。本研究纳入46例接受硼替佐米联合地塞米松第一周期治疗的MM患者，检测其cEPCs与基质细胞衍生因子-1α（SDF-1α）水平，并基于患者完成4个21天周期化疗后的应答情况，分析其临床相关性。通过荧光激活细胞分选术（FACS）分析单个核细胞组分以检测cEPCs水平，采用酶联免疫吸附试验（ELISA）检测SDF-1α水平。本研究队列根据化疗应答情况分为3组：良好应答组（n=16）、一般应答组（n=12）与无应答组（n=18）。基线第1天时，三组间无显著统计学差异（P>0.05）。良好应答组患者的cEPCs水平在第21天（8.2±3.3 cEPCs/μL）较第1天（8.4±2.9 cEPCs/μL）略有下降，但差异无统计学意义（P>0.05）。与之相反，其余两组的cEPCs水平均显著升高（P<0.05）。SDF-1α水平变化与cEPCs水平变化密切相关。本研究结果表明，第一周期化疗第21天的cEPCs变化可作为预测后续治疗应答的无创生物标志物，其变化幅度或可辅助临床决策是否继续该昂贵的化疗方案。cEPCs及SDF-1α/CXCR4轴有望成为改善MM患者治疗应答与预后的潜在治疗靶点。