Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham–Stout disease

Abstract

Background 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. Procedure 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. Results 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. Conclusions 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.

Analysis of mTOR pathway expression in lymphatic malformation and related diseases

“…Sirolimus is an effective and safe treatment for most patients with complicated lymphatic anomalies. However, some patients did not get good response to sirolimus 5,12,31,32 . Further study is needed to determine whether it is possible to predict which patients will benefit from sirolimus treatment and whether the mTOR pathway expression level can serve as a biomarker of treatment response.…”

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature

“…Before administering sirolimus, zoledronic acid, interferon, or propranolol were given, indicating that the current therapeutic protocols are not uniform (Table 2). In addition to cases listed in Table 1, Ricci et al [23] and Ozeki et al [24] reported eight cases treated with sirolimus but did not provide clinical histories of these cases. Six of the eight cases responded well to sirolimus.…”

A Large Skull Defect Due to Gorham-Stout Disease: Case Report and Literature Review on Pathogenesis, Diagnosis, and Treatment

“…mTOR is an important kinase in the progression of the cell cycle. The net result is immune suppression by inhibition of lymphocytes and decreased lymphangiomatous invasion by inhibition of lymphangiogenic growth factors (33,34). The betablocking agent propranolol has also been reported as therapeutic option for Gorham-Stout disease, possibly through lowering of VEGF-A levels (35).…”