Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Cytotherapy. 2013 Jul;15(7):850-60. doi: 10.1016/j.jcyt.2013.02.008. Epub 2013 Apr 24.
Stem cell mobilization and harvesting by peripheral blood leukapheresis in patients with myeloma can alter plasma levels of certain cytokines. In the present study, we investigated the effects of these interventions on a larger group of cytokines.
Plasma cytokine levels were determined in 15 patients with myeloma who were undergoing peripheral blood stem cell harvesting, and we compared the patients with healthy donors who were undergoing platelet apheresis.
Several cytokines showed altered levels in patients with myeloma when examined after chemotherapy plus granulocyte colony-stimulating factor-induced stem cell mobilization. The most striking effect was increased levels of several CCL (CCL2/3/4) and CXCL (CXCL5/8/10/11) chemokines as well as increased thrombopoietin, interleukin 1 receptor antagonist, interleukin-4, granulocyte colony-stimulating factor and hepatocyte growth factor. Stem cell harvesting by apheresis altered the plasma levels of several mediators (CD40 ligand, interleukin 1 receptor antagonist, CCL5 and CXCL5/8/10/11). Apheresis in patients with myeloma had divergent effects on these chemokine levels, although they were all still significantly higher than for healthy individuals. Thrombapheresis in healthy individuals had only minor effects on plasma cytokine levels. Stem cell graft supernatants showed high levels of several cytokines, especially CCL and CXCL chemokines. Analyses of chemokine profiles in pre-apheresis plasma and graft supernatants suggested that such profiling can be used to detect prognostically relevant differences between patients.
Our results demonstrate that patients with myeloma have an altered cytokine network during stem cell mobilization, and the network is further altered during stem cell harvesting by leukapheresis. These treatment- or procedure-induced alterations involve several mediators known to affect myeloma cell proliferation, migration and survival.
多发性骨髓瘤患者通过外周血白细胞分离术进行干细胞动员和采集会改变某些细胞因子的血浆水平。在本研究中，我们研究了这些干预措施对更大一组细胞因子的影响。
我们检测了 15 名正在接受外周血干细胞采集的多发性骨髓瘤患者的血浆细胞因子水平，并将这些患者与正在接受血小板单采术的健康供体进行了比较。
在化疗加粒细胞集落刺激因子诱导的干细胞动员后，多发性骨髓瘤患者的几种细胞因子水平发生了改变。最显著的影响是几种 CCL（CCL2/3/4）和 CXCL（CXCL5/8/10/11）趋化因子以及血小板生成素、白细胞介素 1 受体拮抗剂、白细胞介素 4、粒细胞集落刺激因子和肝细胞生长因子的水平升高。通过单采术采集干细胞改变了几种介质（CD40 配体、白细胞介素 1 受体拮抗剂、CCL5 和 CXCL5/8/10/11）的血浆水平。多发性骨髓瘤患者的单采术对这些趋化因子水平有不同的影响，但它们仍然明显高于健康个体。健康个体的血小板单采术对血浆细胞因子水平只有轻微影响。干细胞移植物上清液显示出几种细胞因子的高水平，尤其是 CCL 和 CXCL 趋化因子。对单采术前血浆和移植物上清液中趋化因子谱的分析表明，这种谱分析可用于检测患者之间具有预后相关性的差异。
我们的研究结果表明，多发性骨髓瘤患者在干细胞动员期间具有改变的细胞因子网络，并且在白细胞分离术进行干细胞采集期间，该网络进一步改变。这些治疗或程序诱导的改变涉及几种已知会影响骨髓瘤细胞增殖、迁移和存活的介质。
