different doses of sirolimus for the treatment of cystic lymphatic malformations

Conditions: Lymphatic Malformation

Summary: the purpose of this study is to compare the efficacy and safety of different concentration gradients of sirolimus in the treatment of cystic lymphatic malformation.

cystic lymphatic malformation is a disease caused by abnormal development of the lymphatic system, characterized by abnormal dilation and/or structural disorder of lymphatic vessels. these abnormalities may lead to accumulation of lymphatic fluid, causing local swelling, pain, and even affecting organ function. cystic lymphatic malformation can occur anywhere in the body, including skin, soft tissue, internal organs, etc. sirolimus, also known as rapamycin, is an immunosuppressant mainly used to prevent rejection after organ transplantation. in recent years, studies have shown that sirolimus has certain potential in the treatment of lymphatic malformations. however, long-term high-dose sirolimus treatment can cause some common complications, such as oral mucositis, which affects the quality of life of patients. more fine-grained control of rapamycin plasma concentrations may help improve the therapeutic effect and reduce the incidence of complications. therefore, the investigators conducted this study to understand whether low-dose rapamycin is beneficial to the prognosis of patients.

Eligibility criteria:
inclusion criteria: * presenting a lm with the following characteristics: 1. male and female; 2. between 0 and 18 years of age; 3. lm diagnosis was confirmed by local investigators and by consensus of our multidisciplinary vascular anomaly group at the west china hospital of sichuan university based on: biopsy; compatible mri findings; history and clinical features. exclusion criteria: 1. patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog) 2. exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study; 3. patients had a history of a major surgery within 2 weeks before enrollment; 4. patients who have a history of treatment with sirolimus or other mtor inhibitor; 5. any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment; 6. concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration). 7. impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus. 8. patients with inadequate liver function: total bilirubin higher than or equal to 1.5 × the upper limit of the normal (uln) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the uln for age. 9. patients with inadequate renal function: 0-5 years of age maximum serum creatinine (mg/dl) of 0.8; 6-10 years of age maximum serum creatinine (mg/dl) of 1.0; 11-14 years of age maximum serum creatinine (mg/dl) of 1.2; 10. adequate bone marrow function: absolute neutrophil count lower than 1 × 109/l; 11. history of a malignancy within 5 years; 12. hiv infection or known immunodeficiency; 13. indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than ih; 14. patients with an inability to participate in or follow-up during the study treatment and assessment plan; 15. inability to give informed consent.

Keywords: lymphatic malformation sirolimus efficacy safety