The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies

Michio OzekiEmail author View ORCID ID profile,
Akifumi Nozawa,
Shiho Yasue,
Saori Endo,
Ryuta Asada,
Hiroya Hashimoto and
Toshiyuki Fukao

Orphanet Journal of Rare Diseases201914:141

https://doi.org/10.1186/s13023-019-1118-1

Received: 4 December 2018
Accepted: 4 June 2019
Published: 13 June 2019

Abstract

Background

Lymphatic anomalies (LAs) include several disorders in which abnormal lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs.

Methods

All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration.

Results

Twenty patients (five with cystic lymphatic malformation (LM), three with kaposiform lymphangiomatosis, three with generalized lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores (P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia.