Different Doses of Sirolimus for the Treatment of Cystic Lymphatic Malformations

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.