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.

Keywords: Gorham-Stout disease (GSD); generalized lymphatic anomaly (GLA); lymphangiomatosis; lymphatic malformation; mammalian target of rapamycin (mTOR); sirolimus (rapamycin).

Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

© 2019 Wiley Periodicals, Inc.

Figures

FIGURE 1:

Radiographic response with sirolimus treatment. A, Prior to initiation of sirolimus. MRI axial T2- weighted imaging of patient with a large intra-abdominal lymphatic malformation. This patient also had pleural effusions, diffuse bony disease, and lesions in the spleen and liver consistent with the diagnosis of GLA. B, 12 months on sirolimus therapy. MRI demonstrated substantial decrease in size of the intraabdominal malformation. C, Prior to initiation of sirolimus. Chest x-ray of a GLA patient with a right-sided pleural effusion. D, 3 months on sirolimus treatment. Chest x-ray exhibits near complete resolution of the right-sided pleural effusion.