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Pediatr Blood Cancer. 2019 May;66(5):e27614. doi: 10.1002/pbc.27614. Epub 2019 Jan 22.

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

Author information

1
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.
2
Department of Pediatric Hematology and Oncology, Children's Minnesota Hematology Oncology, Minneapolis, Minnesota.
3
Division of Pediatric Hematology Oncology, University of North Carolina, Chapel Hill, North Carolina.
4
Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, New York City, New York.
5
Sainte-Justine University Hospital Center, Montreal, Canada.
6
Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland.
7
Department of Dermatology, University of California, San Francisco, San Francisco, California.
8
Vascular Anomalies Center, Division of Hematology/Oncology, Cancer and Blood Disorders Center, Boston Children's Hospital, Boston, Massachusetts.

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)

PMID:
30672136
PMCID:
PMC6428616
[Available on 2020-05-01]
DOI:
10.1002/pbc.27614

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