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异基因造血细胞移植后使用环磷酰胺后的 G-CSF 的安全性和有效性:内皮细胞活化的临床和体外检查。

Safety and efficacy of G-CSF after allogeneic hematopoietic cell transplantation using post-transplant cyclophosphamide: clinical and in vitro examination of endothelial activation.

机构信息

Hemostasis and Erythropathology Laboratory, Hematopathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Barcelona, Spain.

Research Biomedical Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

出版信息

Bone Marrow Transplant. 2024 Oct;59(10):1466-1476. doi: 10.1038/s41409-024-02388-y. Epub 2024 Aug 8.

Abstract

Since 2021 the use of G-CSF was implemented in allo-HCT with PTCY-based prophylaxis with the aim of shortening the aplastic phase and reducing infectious complications. This study investigates the effectiveness of this change in protocol performed at our institution. One-hundred forty-six adults undergoing allo-HCT with PTCY-based prophylaxis were included, and among them, 58 (40%) received G-CSF. The median of days to neutrophil engraftment was shorter in the G-CSF group (15 vs. 20 days, p < 0.001). Patients receiving G-CSF had a lower incidence of day +30 bacterial bloodstream infections (BSI) than the rest (20.7% vs. 47.7%, p < 0.001). GVHD, SOS, and TA-TMA incidences were comparable between groups, and using G-CSF did not impact on survival. Endothelial activation was investigated using EASIX and by the measurement of soluble biomarkers in cryopreserved plasma samples obtained on days 0, +7, +14 and +21 of 39 consecutive patients (10 received G-CSF) included in the study. EASIX, VWF:Ag, sVCAM-1, sTNFRI, ST2, REG3α, TM and NETs medians values were comparable in patients receiving G-CSF and those who did not. Compared with allo-HCT performed without G-CSF, the addition of G-CSF to PTCY-based allo-HCT accelerated neutrophil engraftment contributing on decreasing BSI incidence, and without inducing additional endothelial activation.

摘要

自 2021 年以来,我们机构在使用 PTCY 进行预防移植物抗宿主病(GVHD)的异基因造血干细胞移植(allo-HCT)中使用 G-CSF,目的是缩短造血停滞期并减少感染并发症。本研究旨在调查该方案变化在本机构实施的效果。共纳入 146 例接受 PTCY 预防移植物抗宿主病的成人 allo-HCT 患者,其中 58 例(40%)接受 G-CSF 治疗。G-CSF 组中性粒细胞植入的中位时间较短(15 天 vs. 20 天,p<0.001)。与未接受 G-CSF 治疗的患者相比,接受 G-CSF 治疗的患者在第 30 天发生细菌性血流感染(BSI)的发生率较低(20.7% vs. 47.7%,p<0.001)。GVHD、SOS 和 TA-TMA 的发生率在两组之间无差异,且使用 G-CSF 并未影响患者的生存。使用 EASIX 和冷冻保存的血浆样本中可溶性生物标志物(于移植后第 0、+7、+14 和+21 天采集)测量了 39 例连续患者(10 例接受 G-CSF 治疗)的内皮细胞激活情况,纳入本研究。接受 G-CSF 治疗和未接受 G-CSF 治疗的患者的 EASIX、VWF:Ag、sVCAM-1、sTNFRI、ST2、REG3α、TM 和 NETs 中位数无差异。与未使用 G-CSF 的 allo-HCT 相比,在 PTCY 基础上添加 G-CSF 可加速中性粒细胞植入,降低 BSI 发生率,且不会引起额外的内皮细胞激活。

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