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[粪便微生物群移植治疗异基因造血干细胞移植后19例类固醇难治性胃肠道急性移植物抗宿主病的临床研究]

[Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation].

作者信息

Zheng Y Y, Yang X T, Lin G Q, Bian M R, Si Y J, Zhang X X, Zhang Y M, Wu D P

机构信息

Department of Hematology, Huai'an Hospital Affiliated to Xuzhou Medical Universitity, Huai'an 223002, China.

Department of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Disease, Suzhou 215006, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2023 May 14;44(5):401-407. doi: 10.3760/cma.j.issn.0253-2727.2023.05.008.

Abstract

To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all < 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L 6.82 (2.40-8.91) ng/L, =0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L 7.51 (4.10-9.58) ng/L, =0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L 74.35 (33.50-139.50) μg/L, =0.021]. FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

摘要

为探讨粪菌移植(FMT)治疗类固醇难治性胃肠道急性移植物抗宿主病(GI-aGVHD)的临床疗效。本分析纳入了2017年3月至2022年3月在徐州医科大学附属淮安医院接受异基因造血干细胞移植(allo-HSCT)后发生类固醇难治性GI-aGVHD的29例血液科患者。其中,19例患者接受了FMT治疗(FMT组),10例患者未接受治疗(对照组)。评估了FMT的疗效和安全性,以及FMT治疗前后肠道微生物群丰度、淋巴细胞亚群比例、外周血炎症细胞因子和GVHD生物标志物的变化。①FMT后13例(68.4%)患者临床症状完全缓解,对照组为2例(20.0%),差异有统计学意义(<0.05)。FMT后肠道微生物群多样性增加并逐渐恢复至正常水平,且未发生与FMT相关的感染。②治疗后FMT组CD3(+)和CD8(+)细胞比例低于对照组,CD4(+)、调节性T细胞(Treg)及CD4(+)/CD8(+)细胞比例升高(均<0.05)。FMT组白细胞介素(IL)-6浓度低于对照组[4.15(1.91-5.71)ng/L对6.82(2.40-8.91)ng/L,P=0.040],FMT组IL-10浓度高于对照组[12.11(5.69-20.36)ng/L对7.51(4.10-9.58)ng/L,P=0.024]。胰岛衍生蛋白3α(REG3α)在GI-aGVHD患者中显著升高,治疗后FMT组REG3α水平低于对照组[30.70(10.50-105.00)μg/L对74.35(33.50-139.50)μg/L,P=0.021]。FMT是一种通过恢复肠道微生物群多样性、调节炎症细胞因子和上调Treg细胞来治疗类固醇难治性GI-aGVHD的安全有效的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c10/10440624/b70db205221a/cjh-44-05-401-g001.jpg

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