Yang Jing-Jing, Peng Bo, Fang Shu, Wei Yan, Wang Hao, Zhao Ying-Xin, Qian Kun, Wen Ya-Nan, Liu Dai-Hong, Dou Li-Ping
Medical School of Chinese PLA, Beijing 100853, China,Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Feb;30(1):276-285. doi: 10.19746/j.cnki.issn.1009-2137.2022.01.046.
To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).
We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).
Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4CD29 T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4CD29 T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8CD28 T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8CD28 T / CD8CD28 T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P=0.01, P=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P=0.0351; P=0.0142; P=0.0369).
We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.
从一项单臂、开放性临床试验（NCT04061876）分析初诊中高危急性移植物抗宿主病（aGVHD）且接受类固醇-鲁索替尼一线治疗患者的淋巴细胞亚群和髓系来源抑制细胞（MDSC）的动力学特征。
我们前瞻性观察了23例中高危aGVHD且接受类固醇-鲁索替尼一线治疗患者的疗效。监测淋巴细胞亚群和MDSC的动力学特征，然后在类固醇-鲁索替尼组（n = 23）、无aGVHD组（n = 20）和类固醇组（n = 23）中进行比较。
23例患者中，一线使用类固醇-鲁索替尼治疗28天后完全缓解（CR）率为78.26%（18/23）。治疗后第28天，患者的CD4CD29 T细胞水平（P = 0.08）低于治疗前，而本研究中其他淋巴细胞亚群水平高于治疗前；CR患者的CD4CD29 T细胞较难治性aGVHD患者减少。治疗第28天，aGVHD患者的CD8CD28 T细胞（P = 0.03）较无aGVHD患者显著增加，CD8CD28 T / CD8CD28 T细胞比值也显著增加（P = 0.03）。与无aGVHD患者相比，aGVHD患者的粒-单核细胞集落刺激因子（G-MDSC）水平较低，尤其是在异基因造血干细胞移植（allo-HSCT）后第14天（P = 0.04）。与治疗前相比，CR患者治疗后第3天和第7天的单核细胞MDSC（M-MDSC）较高（P = 0.01，P = 0.03），治疗后第28天的嗜酸性粒细胞MDSC（e-MDSC）较高（P = 0.01）。此外，与CR患者相比，难治性aGVHD患者治疗后第3天的M-MDSC较低（P = 0.01），治疗后第28天的e-MDSC较低（P = 0.01）。与类固醇组相比，类固醇-鲁索替尼组的MDSC较高，M-MDSC差异最为显著（P = 0.0351；P = 0.0142；P = 0.0369）。
我们发现，初诊中高危aGVHD且接受类固醇-鲁索替尼一线治疗的患者有较高的缓解率。此外，这种新型一线治疗对allo-HSCT后患者的免疫重建影响较小。MDSC升高可能预示接受这种新型一线治疗的aGVHD患者有更好的反应。M-MDSC对类固醇-鲁索替尼的反应早于e-MDSC、G-MDSC。
