Abstract

Ruxolitinib, a selective Janus Kinase (JAK) 1/2 inhibitor, is a promising treatment for the steroid-refractory graft-vs-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT). Most studies have been performed in the adult population showing efficacy against GvHD. In this retrospective study, we evaluated the outcomes of 19 children who received ruxolitinib for refractory acute or chronic GvHD (cGvHD) after HSCT from two Pediatric Hemato-Oncology Departments in Spain between March 2017 and December 2018. Patients received a median number of 4 (IQR 2) previous lines of treatment before starting ruxolitinib. The overall response rate in acute GvHD (aGvHD) and cGvHD was 87% and 91%, respectively. Complete response (CR) was observed in 37% of aGvHD and 8.3% of cGvHD. Remarkably, 43% and 40% of patients with steroid-refractory gastrointestinal aGvHD and lung cGvHD achieved CR. During ruxolitinib treatment, there were 36%, 31%, and 10% infections caused by viruses, bacteria, and fungi, respectively. Overall, four patients interrupted ruxolitinib due to infectious complications, hematological, and liver toxicity. The 2-year overall survival was 71.9% (CI 95% 58.6–85.2). Our experience supports the use of ruxolitinib as an effective treatment for steroid-refractory acute and cGvHD in children with a moderate toxicity profile.

摘要

Ruxolitinib 是一种选择性 Janus Kinase (JAK) 1/2 抑制剂，是治疗造血干细胞移植 (HSCT) 后类固醇难治性移植物抗宿主病 (GvHD) 的一种有前途的治疗方法。大多数研究都是在成年人群中进行的，显示出对抗 GvHD 的功效。在这项回顾性研究中，我们评估了 19 名儿童在 2017 年 3 月至 2018 年 12 月期间在西班牙两个儿科血液肿瘤科接受 HSCT 后接受鲁索替尼治疗难治性急性或慢性 GvHD (cGvHD) 的结果。患者接受的中位数为 4 ( IQR 2) 开始使用鲁索替尼之前的先前治疗线。急性 GvHD (aGvHD) 和 cGvHD 的总体反应率分别为 87% 和 91%。在 37% 的 aGvHD 和 8.3% 的 cGvHD 中观察到完全反应 (CR)。值得注意的是，43% 和 40% 的类固醇难治性胃肠道 aGvHD 和肺 cGvHD 患者达到 CR。在 ruxolitinib 治疗期间，病毒、细菌和真菌引起的感染分别为 36%、31% 和 10%。总体而言，四名患者因感染并发症、血液学和肝脏毒性而中断了鲁索替尼治疗。2 年总生存率为 71.9% (CI 95% 58.6–85.2)。我们的经验支持使用鲁索替尼作为中度毒性儿童的类固醇难治性急性和 cGvHD 的有效治疗方法。2 年总生存率为 71.9% (CI 95% 58.6–85.2)。我们的经验支持使用鲁索替尼作为中度毒性儿童的类固醇难治性急性和 cGvHD 的有效治疗方法。2 年总生存率为 71.9% (CI 95% 58.6–85.2)。我们的经验支持使用鲁索替尼作为中度毒性儿童的类固醇难治性急性和 cGvHD 的有效治疗方法。