Hemangioma and Vascular Malformation Center, Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Pediatric Hematology and Oncology, Children's Minnesota Hematology Oncology, Minneapolis, Minnesota.
Pediatr Blood Cancer. 2019 May;66(5):e27614. doi: 10.1002/pbc.27614. Epub 2019 Jan 22.
Generalized lymphatic anomaly (GLA) and Gorham-Stout disease (GSD) are rare complicated lymphatic malformations that occur in multiple body sites and are associated with significant morbidity and mortality. Treatment options have been limited, and conventional medical therapies have been generally ineffective. Emerging data suggest a role for sirolimus as a treatment option for complex lymphatic anomalies.
Disease response was evaluated by radiologic imaging, quality of life (QOL), and clinical status assessments in children and young adults with GLA and GSD from a multicenter systematic retrospective review of patients treated with oral sirolimus and the prospective phase 2 clinical trial assessing the efficacy and safety of sirolimus in complicated vascular anomalies (NCT00975819). Sirolimus dosing regimens and toxicities were also assessed.
Eighteen children and young adults with GLA (n = 13) or GSD (n = 5) received oral sirolimus. Fifteen patients (83%) had improvement in one or more aspects of their disease (QOL 78%, clinical status 72%, imaging 28%). No patients with bone involvement had progression of bone disease, and the majority had symptom or functional improvement on sirolimus. Improvement of pleural and pericardial effusion(s) occurred in 72% and 50% of affected patients; no effusions worsened on treatment.
Sirolimus appears effective at stabilizing or reducing signs/symptoms of disease in patients with GLA and GSD. Functional impairment and/or QOL improved in the majority of individuals with GLA and GSD with sirolimus treatment.
全身性淋巴管异常（GLA）和 Gorham-Stout 病（GSD）是罕见的复杂淋巴管畸形，可发生在多个身体部位，并伴有较高的发病率和死亡率。治疗选择有限，常规的医学治疗通常无效。新出现的数据表明，西罗莫司作为治疗复杂淋巴管异常的一种选择具有一定作用。
对接受口服西罗莫司治疗的多中心系统回顾性研究中患有 GLA 和 GSD 的儿童和年轻患者以及评估西罗莫司在复杂血管异常中的疗效和安全性的前瞻性 2 期临床试验（NCT00975819）中患者的影像学、生活质量（QOL）和临床状况评估，对疾病反应进行了评估。还评估了西罗莫司的剂量方案和毒性。
18 名患有 GLA（n=13）或 GSD（n=5）的儿童和年轻患者接受了口服西罗莫司治疗。15 名患者（83%）在疾病的一个或多个方面有改善（QOL 78%，临床状态 72%，影像学 28%）。没有骨受累的患者出现骨病进展，大多数患者在使用西罗莫司后症状或功能有改善。72%和 50%的受累患者的胸腔和心包积液得到改善；没有积液在治疗过程中恶化。
西罗莫司似乎能有效稳定或减轻 GLA 和 GSD 患者的疾病体征/症状。大多数 GLA 和 GSD 患者在接受西罗莫司治疗后，功能障碍和/或 QOL 得到改善。
