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采用粒细胞-巨噬细胞集落刺激因子和粒细胞集落刺激因子联合动员正常供者造血祖细胞可减少移植物中的浆细胞样树突状细胞,并增强供者 T 细胞植入和 Th1 极化:一项随机临床试验的结果。

Mobilization of hematopoietic progenitors from normal donors using the combination of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor results in fewer plasmacytoid dendritic cells in the graft and enhanced donor T cell engraftment with Th1 polarization: results from a randomized clinical trial.

机构信息

Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.

出版信息

Biol Blood Marrow Transplant. 2013 Mar;19(3):460-7. doi: 10.1016/j.bbmt.2012.11.017. Epub 2012 Nov 28.

Abstract

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) both mobilize CD34(+) stem cells into the blood when administered before apheresis but have distinct effects on dendritic cell (DC) differentiation. We previously demonstrated that the combination of GM+G-CSF results in fewer plasmacytoid DCs (pDCs) when used to mobilize peripheral blood stem cells for autologous transplantation. To test the hypothesis that the content of pDCs in an allograft can be modulated with the cytokines used for mobilization, we randomized the human leukocyte antigen-matched sibling donors of 50 patients with hematological malignancies to a mobilization regimen of either GM+G-CSF (n = 25) or G-CSF alone (n = 25). Primary and secondary endpoints included the cellular constituents of the mobilized grafts, the kinetics of posttransplantation immune reconstitution, and clinical outcomes of the transplantation recipients. Grafts from donors receiving GM+G-CSF contained equivalent numbers of CD34(+) cells with fewer pDCs and T cells, with a higher fraction of Th1-polarized donor T cells than G-CSF mobilized grafts. Immune recovery was enhanced among recipients of GM+G-CSF. Survival was not significantly different between transplantation recipients in the two arms. The use of GM+G-CSF modulates immune function and recovery after allogeneic transplantation and should be explored in larger studies powered to evaluate clinical outcomes.

摘要

粒细胞集落刺激因子(G-CSF)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)在采集前使用时均可将 CD34+干细胞动员到血液中,但对树突状细胞(DC)分化有不同的影响。我们之前的研究表明,用于动员自体移植外周血干细胞时,GM+G-CSF 联合使用可导致较少的浆细胞样 DC(pDC)。为了验证用于动员的细胞因子可调节同种异体移植物中 pDC 含量的假设,我们将 50 例血液系统恶性肿瘤患者的 HLA 匹配同胞供者随机分为 GM+G-CSF 组(n=25)或 G-CSF 组(n=25)。主要和次要终点包括动员移植物的细胞成分、移植后免疫重建的动力学和移植受者的临床结局。接受 GM+G-CSF 治疗的供者的移植物中含有等量的 CD34+细胞,pDC 和 T 细胞较少,Th1 极化的供者 T 细胞比例高于 G-CSF 动员的移植物。GM+G-CSF 组受者的免疫恢复增强。两组移植受者的存活率无显著差异。GM+G-CSF 的使用可调节同种异体移植后的免疫功能和恢复,应在更大规模的研究中进行评估以评估临床结局。

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