Hematopoietic Stem Cell Transplant Unit, Giannina Gaslini Institute, Scientific Institute for Research, Hospitalization and Healthcare, Genoa, Italy.
Epidemiology Service, Giannina Gaslini Institute, Scientific Institute for Research, Hospitalization and Healthcare, Genoa, Italy.
Biol Blood Marrow Transplant. 2019 Apr;25(4):743-748. doi: 10.1016/j.bbmt.2018.11.017. Epub 2018 Nov 22.
Corticosteroids are the standard of care for first-line treatment of patients who develop grade II-IV of acute graft-versus-host disease (aGVHD), but the optimal second-line treatment has not yet been determined. We prospectively evaluated the use of the anti-TNFα monoclonal antibody etanercept (ET) as second-line treatment in children with steroid-refractory (SR) aGVHD. Twenty-five children with either malignant or nonmalignant diseases experiencing grade II-IV SR aGVHD received ET as second-line treatment. ET was administered after a median of 14days (range, 5 to 135 days) from the onset of aGVHD. Seventeen out of 25 patients (68%) developed a complete response (CR) or partial response (PR) to ET. The overall response rate (CR plus PR) was 78% in patients with cutaneous SR aGVHD, 78% in those with gastrointestinal aGVHD, and 57% in those with hepatic aGVHD. On day +100 after the start of ET, 52% of the children were in CR, 16% were in PR, and the remaining 32% failed to respond. Overall survival was 76.5% in responders and 16.7% in nonresponders (P = .004). Transplantation-related mortality at 5years was 34.1% (95% confidence interval, 18.6% to 57.1%). In our experience, ET has proven to be effective as second-line treatment in children with SR aGVHD.
皮质类固醇是治疗发生 II-IV 级急性移植物抗宿主病（aGVHD）患者的标准一线治疗药物，但尚未确定最佳的二线治疗方法。我们前瞻性评估了抗 TNFα 单克隆抗体依那西普（ET）作为二线治疗药物在类固醇难治性（SR）aGVHD 儿童中的应用。25 名患有恶性或非恶性疾病、经历 II-IV 级 SR aGVHD 的儿童接受 ET 作为二线治疗。ET 在 aGVHD 发作后中位数 14 天（范围，5 至 135 天）开始使用。25 名患者中有 17 名（68%）对 ET 产生完全缓解（CR）或部分缓解（PR）。皮肤 SR aGVHD 患者的总缓解率（CR 加 PR）为 78%，胃肠道 aGVHD 患者为 78%，肝脏 aGVHD 患者为 57%。在开始 ET 后的第 100 天，52%的儿童达到 CR，16%达到 PR，其余 32%无反应。应答者的总体生存率为 76.5%，无应答者为 16.7%（P=0.004）。5 年时与移植相关的死亡率为 34.1%（95%置信区间，18.6%至 57.1%）。根据我们的经验，ET 已被证明在治疗 SR aGVHD 的儿童中作为二线治疗有效。
