Medical School of Chinese PLA, Beijing, 100853, China.
Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, NO. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Ann Hematol. 2022 Mar;101(3):621-630. doi: 10.1007/s00277-021-04727-1. Epub 2021 Nov 23.
We started a single-arm, phase II, open-label, prospective clinical trial using steroids-ruxolitinib as the first-line therapy for intermediate- to high-risk aGVHD (NCT04397367). Here, we report the association of a biomarker panel (sST2, REG3α, sTNFR1, IL-6 and IL-8) with responses to GVHD therapy. The novel first-line therapy for 39 patients with newly diagnosed aGVHD consisted of 1 mg/kg methylprednisolone and 5 mg/day ruxolitinib. The serum concentrations of the biomarkers were prospectively detected at planned time points. Of the 39 patients, the complete response rate at day 28 was 82.05%. In patients who achieved CR, the concentrations of REG3α (P = 0.01; P = 0.10) and sTNFR1 (P = 0.42; P = 0.04) declined at day 14 and day 28 compared with the pre-enrolment levels. In refractory patients, the levels of REG3α at day 14 were higher than those pre-enrolment (P = 0.04). REG3α (P = 0.02) was elevated in the refractory patients compared with the patients achieving CR at day 14 after enrolment, while there was no significant difference in the levels of sST2, sTNFR1 or IL-6. Elevated REG3α levels may predict refractory aGVHD after novel first-line therapy with steroids-ruxolitinib.
我们开展了一项单臂、二期、开放标签、前瞻性临床试验，使用类固醇-鲁索利替尼作为中高危急性移植物抗宿主病（aGVHD）的一线治疗（NCT04397367）。在这里，我们报告了生物标志物组（sST2、REG3α、sTNFR1、IL-6 和 IL-8）与 GVHD 治疗反应的关联。39 例新发 aGVHD 患者的新型一线治疗方案包括 1mg/kg 甲基强的松龙和 5mg/天鲁索利替尼。在计划的时间点前瞻性检测生物标志物的血清浓度。在 39 例患者中，第 28 天的完全缓解率为 82.05%。在达到 CR 的患者中，REG3α（P=0.01；P=0.10）和 sTNFR1（P=0.42；P=0.04）的浓度在第 14 天和第 28 天较入组前水平下降。在难治性患者中，第 14 天的 REG3α 水平高于入组前（P=0.04）。与达到 CR 的患者相比，在第 14 天和第 14 天以后，难治性患者的 REG3α（P=0.02）升高，而 sST2、sTNFR1 或 IL-6 的水平没有显著差异。在新型一线类固醇-鲁索利替尼治疗后，REG3α 水平升高可能预示难治性 aGVHD。
