Dataset Information

Sirolimus in the treatment of kaposiform lymphangiomatosis.

ABSTRACT:

Background

Kaposiform lymphangiomatosis (KLA), which is a new subtype of generalized lymphatic anomaly, is a rare disease with a poor prognosis. Currently, there is no standard treatment due to the poor understanding of KLA. Sirolimus, which is an inhibitor of mammalian target of rapamycin, has been shown to have promising potential in the treatment of complicated vascular anomalies. The aim of this study was to introduce the use of sirolimus for the treatment of KLA and to highlight the challenges of managing this refractory disease.

Results

We reported seven patients with KLA who received sirolimus therapy in our center. Combined with previously reported cases, 58.3% achieved a partial response, 25.0% had stable disease, and 16.7% experienced disease progression. No severe sirolimus-related adverse events occurred during treatment.

Conclusions

This study suggests that sirolimus is currently an option for the treatment of KLA, and it is hoped that more specific therapies will be developed in the future. Rapid advances in basic science and clinical practice may facilitate the development of important new treatments for KLA.

SUBMITTER: Zhou J

PROVIDER: S-EPMC8186093 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Sirolimus in the treatment of kaposiform lymphangiomatosis.

Zhou Jiangyuan J Yang Kaiying K Chen Siyuan S Ji Yi Y

Orphanet journal of rare diseases 20210608 1

<h4>Background</h4>Kaposiform lymphangiomatosis (KLA), which is a new subtype of generalized lymphatic anomaly, is a rare disease with a poor prognosis. Currently, there is no standard treatment due to the poor understanding of KLA. Sirolimus, which is an inhibitor of mammalian target of rapamycin, has been shown to have promising potential in the treatment of complicated vascular anomalies. The aim of this study was to introduce the use of sirolimus for the treatment of KLA and to highlight the ...[more]

PMID: 34103076

Similar Datasets

Project description:BackgroundKaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy.MethodsThe NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay.ResultsTrametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib.ConclusionsTrametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies.ImpactThis is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

Dataset Information

Sirolimus in the treatment of kaposiform lymphangiomatosis.

Background

Results

Conclusions

Publications

Sirolimus in the treatment of kaposiform lymphangiomatosis.

Similar Datasets

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