Different Doses of Sirolimus for the Maintenance Treatment of Kaposiform Hemangioendothelioma

Inclusion Criteria: Presenting a KHE with the following characteristics:

1. Male and female;
2. Between 0 and 14 years of age;
3. Diagnosis of KHE as determined by:

• Biopsy;
• Compatible MRI findings;
• History and clinical features.

4. Patients were required to have adequate liver, renal and bone marrow function, andabsence of active infection
5. Consent of parents (or the person with parental authority in families): signed anddated written informed consent.

Exclusion Criteria:

1. Patients contraindicated for the administration of sirolimus (e.g., those with anallergy to sirolimus or other rapamycin analog)
2. Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy orany 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 asreceiving intravenous antibiotics at the time of enrollment;
6. Concurrent severe and/or uncontrolled medical diseases that could compromiseparticipation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension,severe malnutrition, chronic liver or renal disease, active upper gastrointestinaltract ulceration).
7. Impairment of gastrointestinal function or chronic gastrointestinal disease that maysignificantly 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) forage and alanine aminotransferase and aspartate aminotransferase higher than or equalto 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 maximumserum 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 treatmentand assessment plan;
15. Inability to give informed consent.