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增强多发性骨髓瘤中自体免疫效应细胞的新型动员策略。

Novel mobilization strategies to enhance autologous immune effector cells in multiple myeloma.

作者信息

Talebian Laleh, Wu Jia Yan, Fischer Dawn A, Hill John M, Szczepiorkowski Zbigniew M, Ernstoff Marc S, Sentman Charles L, Meehan Kenneth R

机构信息

Blood and Marrow Transplant Program, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, NH 03756, USA.

出版信息

Front Biosci (Elite Ed). 2011 Jun 1;3(4):1500-8. doi: 10.2741/e351.

Abstract

The immune system plays a critical role determining the outcomes in transplanted multiple myeloma patients, since enhanced lymphocyte recovery results in improved survival. Since mobilization regimens influence the cellular subsets collected and infused for transplant, these regimens may determine immune recovery following transplant. We hypothesized that a mobilized stem cell product harboring an increased number of lymphocytes would enhance immune recovery following autologous stem cell infusion, increase lymphocyte recovery, and improve clinical outcomes. We designed a phase I immune mobilization trial using IL-2 and growth factors to increase the number of lymphocytes within the stem cell product. This regimen efficiently mobilized CD34+ progenitor cells (median: 3.6 x 10(6) cells/kg; range 1.9-6.6 x 10(6) cells/kg) and improved the immune properties of the mobilized stem cells, including an increase in CD8+ T cells expressing an NK activating receptor called NKG2D (P less than 0.004), cells that are extremely potent at killing myeloma cells using non-MHC-I restricted and TCR-independent mechanisms. Novel mobilization techniques can improve the mobilized graft and may improve clinical outcomes in myeloma patients.

摘要

免疫系统在决定多发性骨髓瘤移植患者的预后方面起着关键作用,因为淋巴细胞恢复增强会导致生存率提高。由于动员方案会影响采集并输注用于移植的细胞亚群,这些方案可能决定移植后的免疫恢复情况。我们假设含有更多淋巴细胞的动员干细胞产品会增强自体干细胞输注后的免疫恢复,增加淋巴细胞恢复,并改善临床预后。我们设计了一项I期免疫动员试验,使用白细胞介素-2和生长因子来增加干细胞产品中的淋巴细胞数量。该方案有效地动员了CD34+祖细胞(中位数:3.6×10⁶个细胞/千克;范围1.9 - 6.6×10⁶个细胞/千克),并改善了动员干细胞的免疫特性,包括表达一种名为NKG2D的自然杀伤细胞激活受体的CD8⁺T细胞增加(P小于0.004),这些细胞在使用非MHC-I限制和非TCR依赖机制杀伤骨髓瘤细胞方面极其有效。新型动员技术可以改善动员移植物,并可能改善骨髓瘤患者的临床预后。

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Improving stem cell mobilization strategies: future directions.改善干细胞动员策略:未来方向。
Bone Marrow Transplant. 2009 Feb;43(3):181-95. doi: 10.1038/bmt.2008.410. Epub 2009 Jan 12.

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