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新型药物和方法在正常供者和患者中的干细胞动员。

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

机构信息

Department of Hematology and Stem Cell Transplantation, School of Medicine, Ankara University, Ankara, Turkey.

出版信息

Bone Marrow Transplant. 2012 Sep;47(9):1154-63. doi: 10.1038/bmt.2011.170. Epub 2011 Aug 29.

Abstract

In spite of the safety and efficiency of the classical mobilization protocols, recombinant human G-CSF±chemotherapy, 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.

摘要

尽管经典动员方案、重组人 G-CSF±化疗具有安全性和有效性,但仍有相当数量的动员失败(10-30%),这需要在自体和同种异体移植环境中使用新的药物和方法。尝试使用几种细胞因子和生长因子作为 G-CSF 的辅助物来提高 CD34+产量,在过去十年中并没有改变标准方法,要么是因为效率低下,要么是因为这些药物的不良反应。作为一种长效 G-CSF 类似物,培非格司亭具有较早开始单采、减少单采次数以及与未缀合 G-CSF 相比减少注射次数的优点。然而,剂量和成本效益,尤其是在仅使用细胞因子的动员中,需要进一步研究。随着对造血干细胞与骨髓微环境相互作用的理解不断加深,针对这些相互作用的新分子正在出现。plerixafor 最初作为一种抗 HIV 药物问世,最近成为一种流行的干细胞动员剂,具有快速动员的能力,并获得批准作为 G-CSF 的辅助药物,用于动员不良者。目前,通过使用适当的时机和具有成本效益的方法,寻找最佳方法,在初始动员尝试后提供足够的 CD34+产量,并避免进一步的动员尝试和化疗暴露,这是一个具有挑战性的问题。不仅旨在增加干细胞产量,而且旨在改善移植物含量和相关移植结果的质量的方法是有前途的研究领域。

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