Separating graft-versus-leukemia from graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.
Separating graft-versus-leukemia from graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.
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DOI：
10.2217/imt.09.32
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发表时间：
2009-07
期刊：
影响因子：
2.8
通讯作者：
Waller EK
中科院分区：
文献类型：
--
作者：
Li JM;Giver CR;Lu Y;Hossain MS;Akhtari M;Waller EK
缺乏常规方法来最大化异基因造血干细胞移植（HSCT）的移植物抗白血病（GvL）活性，而没有移植物抗宿主病（GvHD）的有害影响。同种异体反应性T细胞的消耗或抑制在预防GvHD中部分有效，但通常导致GvL活性降低。目前急性GvHD的病理生理学模型描述了一系列免疫途径，这些免疫途径导致供体T细胞和炎性细胞因子的活化，这些细胞因子负责急性GvHD中的组织损伤。该模型没有解释同种异体移植如何在没有GvHD的情况下导致GvL效应，或者供体免疫细胞的初始激活如何导致限制GvHD的反调节效应。在这篇综述中，我们将总结新的研究结果，支持一个更复杂的模型启动GvHD和GvL活动在异基因造血干细胞移植，并讨论新的策略，以提高移植的GvL活性的潜力。
Routine methods to maximize the graft-versus-leukemia (GvL) activity of allogeneic hematopoietic stem cell transplantation (HSCT) without the detrimental effects of graft-versus-host disease (GvHD) are lacking. Depletion or inhibition of alloreactive T cells is partially effective in preventing GvHD, but usually leads to decreased GvL activity. The current model for the pathophysiology of acute GvHD describes a series of immune pathways that lead to activation of donor T cells and inflammatory cytokines responsible for tissue damage in acute GvHD. This model does not account for how allotransplant can lead to GvL effects without GvHD, or how the initial activation of donor immune cells may lead to counter-regulatory effects that limit GvHD. In this review, we will summarize new findings that support a more complex model for the initiation of GvHD and GvL activities in allogeneic HSCT, and discuss the potential of novel strategies to enhance GvL activity of the transplant.