Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I, Dresden, Germany.
Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I, Dresden, Germany; National Center for Tumor Diseases, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Dresden, Germany.
Biol Blood Marrow Transplant. 2018 Nov;24(11):2171-2177. doi: 10.1016/j.bbmt.2018.06.023. Epub 2018 Jun 21.
This study was conducted to characterize and compare peripheral blood stem cell grafts from healthy donors who underwent granulocyte colony-stimulating factor (G-CSF) mobilization and subsequently received 1 dose of plerixafor after insufficient stem cell yields were achieved at the first apheresis. Aliquots from 35 donors were collected from the first apheresis after mobilization with G-CSF alone and from the second apheresis after additional plerixafor administration. Samples were freshly analyzed for cellular subsets by 8-color flow cytometry. Leukapheresis samples mobilized with additional plerixafor showed a significant increase of total nucleated cells, including B cells, CD4 and CD8 T cells, and CD34 hematopoietic stem and progenitor cells. Absolute numbers of plasmacytoid dendritic cells were also significantly increased, whereas no changes were detected for myeloid dendritic cells. Furthermore, absolute numbers of regulatory T cells increased, with naive CD45RA regulatory T cells showing the highest rise. Finally, strikingly higher numbers of myeloid-derived suppressor cells were detected in the plerixafor and G-CSF-mobilized graft. The mobilization of peripheral stem cells in healthy donors with G-CSF and plerixafor led to a significant difference in cellular graft composition compared with G-CSF alone. The clinical impact of the different cell composition for the graft recipient warrants further clinical investigation.
本研究旨在对接受粒细胞集落刺激因子(G-CSF)动员的健康供者的外周血造血干细胞移植物进行特征描述和比较,并在首次单采时未获得足够的干细胞产量后,给予 1 剂plerixafor。从 35 名供者的首次单采后采集移植物,这些供者在单独使用 G-CSF 动员后和在额外使用 plerixafor 后的第二次单采后采集移植物。通过 8 色流式细胞术对新鲜样本进行细胞亚群分析。使用额外的 plerixafor 动员的白细胞单采样本显示总核细胞(包括 B 细胞、CD4 和 CD8 T 细胞以及 CD34 造血干细胞和祖细胞)显著增加。浆细胞样树突状细胞的绝对数量也显著增加,而髓样树突状细胞无变化。此外,调节性 T 细胞的绝对数量增加,其中幼稚 CD45RA 调节性 T 细胞增加最多。最后,在 plerixafor 和 G-CSF 动员的移植物中检测到明显更多的髓源性抑制细胞。与单独使用 G-CSF 相比,G-CSF 和 plerixafor 动员健康供者的外周干细胞导致细胞移植物组成的显著差异。不同细胞组成对移植物受者的临床影响需要进一步的临床研究。