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Novel agents and approaches for stem cell mobilization in normal donors and patients

机译:正常供体和患者中动员干细胞的新型药物和方法

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In spite of the safety and efficiency of the classical mobilization protocols, recombinant human G-CSFchemotherapy, there is still a considerable amount of mobilization failures (10-30%), which warrant novel agents and approaches both in an autologous and an allogeneic transplant setting. Attempts to improve CD34 yields by using several cytokines and growth factors as adjuncts to G-CSF could not change the standard approaches during the last decade, either because of inefficiency or the adverse events encountered with these agents. As a long-acting G-CSF analog, pegfilgrastim has the advantages of an earlier start of apheresis, reduction in the number of apheresis procedures as well as a reduced number of injections as compared with unconjugated G-CSF. However, dosing and cost-effectiveness especially in cytokine-only mobilizations require further investigation. As interactions between hematopoietic stem cells and the BM microenvironment are better understood, new molecules targeting these interactions are emerging. Plerixafor, which started its journey as an anti-HIV drug, recently ended up being a popular stem cell mobilizer with the ability of rapid mobilization and gained approval as an adjunct to G-CSF for poor mobilizers. At present, it is challenging to search for the best approach by using the available drugs with appropriate timing to provide sufficient CD34 yield after an initial mobilization attempt, and in a cost-effective manner thereby avoiding further mobilization attempts and exposure to chemotherapy. Approaches not only for increasing stem cell yield, but also aiming to improve the quality of graft content and the associated transplantation outcomes are promising areas of research.
机译:尽管经典的动员方案,重组人G-CSF化学疗法具有安全性和有效性,但仍有相当数量的动员失败(10-30%),这在自体和异体移植环境中都需要新颖的药物和方法。通过使用几种细胞因子和生长因子作为G-CSF的辅助物来尝试提高CD34产量的尝试在过去十年中无法改变标准方法,这是由于这些试剂的无效或不良事件。作为长效G-CSF类似物,pegfilgrastim具有以下优点:与未结合的G-CSF相比,pegfilgrastim可以更早地开始血液分离,减少血液分离程序的次数,减少注射次数。然而,剂量和成本效益,特别是在仅细胞因子的动员中,需要进一步研究。随着对造血干细胞和BM微环境之间相互作用的更好理解,出现了靶向这些相互作用的新分子。作为抗HIV药物开始的Plerixafor,最近成为具有快速动员能力的广受欢迎的干细胞动员者,并获得批准用作G-CSF的辅助动员者。当前,通过在适当的时机使用可得的药物以在初始动员尝试之后以成本有效的方式提供足够的CD34产量来寻求最佳方法是有挑战性的,从而避免进一步的动员尝试和暴露于化学疗法。不仅增加干细胞产量的方法,而且旨在提高移植物含量的质量和相关移植结果的方法都是有前途的研究领域。

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