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在供者淋巴细胞单采术之前给予 G-CSF 可增强异基因造血干细胞移植患者的抗白血病效应。

G-CSF administration prior to donor lymphocyte apheresis promotes anti-leukaemic effects in allogeneic HCT patients.

机构信息

Blood and Marrow Transplantation, Department of Medicine II, University Hospital Tuebingen, Tuebingen, Germany.

University Children's Hospital, University Hospital Tuebingen, Tuebingen, Germany.

出版信息

Br J Haematol. 2019 Jul;186(1):60-71. doi: 10.1111/bjh.15881. Epub 2019 Mar 27.

Abstract

Donor lymphocyte infusion (DLI) is an effective method to establish full donor chimerism or to prevent and treat relapse after allogeneic haematopoietic cell transplantation (allo-HCT). Usually, DLIs are collected from naïve donors as steady-state lymphocytes. When donor lymphocytes are collected during stem cell apheresis, donors are pre-treated with granulocyte colony-stimulating factor (G-CSF). However, the impact of G-CSF stimulation and the resulting composition of DLIs on beneficial anti-leukaemic responses and survival remain elusive. Therefore, we performed a retrospective analysis to evaluate the role of G-CSF-DLIs: 44 patients received either steady-state DLIs or G-CSF-DLIs to prevent and treat relapse or establish full donor chimerism after allo-HCT. The G-CSF-DLI patient cohort showed an improved conversion to full donor chimerism and a lower cumulative incidence of relapse or disease progression without a significantly increased cumulative incidence of graft-versus-host disease (GVHD). CD34 cells, monocytic myeloid-derived suppressor cells and monocytes as well as donor age and the subsequent occurrence of chronic GVHD were identified as risk factors that significantly improve overall survival after DLI administration. In conclusion, our data suggest that administration of G-CSF-DLIs results in graft-versus-leukaemia effects without exacerbating GVHD, therefore, improving survival after DLIs.

摘要

供者淋巴细胞输注(DLI)是建立完全供者嵌合或预防和治疗异基因造血细胞移植(allo-HCT)后复发的有效方法。通常,DLI 是从幼稚供者作为稳定状态的淋巴细胞中采集的。当在干细胞采集期间采集供者淋巴细胞时,供者用粒细胞集落刺激因子(G-CSF)预处理。然而,G-CSF 刺激及其对有益的抗白血病反应和生存的影响仍不清楚。因此,我们进行了一项回顾性分析,以评估 G-CSF-DLI 的作用:44 例患者接受稳态 DLI 或 G-CSF-DLI,以预防和治疗 allo-HCT 后复发或建立完全供者嵌合。G-CSF-DLI 患者队列显示出更高的完全供者嵌合转化率和更低的复发或疾病进展累积发生率,而移植物抗宿主病(GVHD)的累积发生率没有显著增加。CD34 细胞、单核细胞来源的髓系抑制细胞和单核细胞以及供者年龄和随后发生的慢性 GVHD 被确定为 DLI 给药后总生存率显著提高的危险因素。总之,我们的数据表明,G-CSF-DLI 的给药导致移植物抗白血病效应而不加重 GVHD,因此改善了 DLI 后的生存。

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