Evaluation of the Use of Sirolimus in Treatment of Complex Vascular Malformation and Tissue Overgrowth Syndromes

Abstract

BACKGROUND AND OBJECTIVES: Management of complex vascular malformations and overgrowth syndromes is challenging. They usually present at birth and have different complications including bleeding, pain, cosmetic disfigurement and functional impairment. This study was to done to determine symptomatic relief and quality of life improvement after sirolimus. METHODS: The intervention phase included sirolimus administered orally on a continuous dosing schedule at a starting dose of 0.8 mg/m2, and its level to be maintained between 4-12 ng/ml. Dose was rounded to the nearest 1mg tablet form. Assessment of response to sirolimus was done (usually 2 weeks after start of sirolimus) clinically by assessment of clinical improvement of the main complaint of the patient e.g. bleeding, pain, cosmetic disfigurement. Laboratory Improvement of patients labs after start of sirolimus e.g elevation of hemoglobin and Mean cell volume. Arabic translation of pediatric quality of life PedsQL 4.0 was done again 6 months after start of sirolimus. Assessment of safety of sirolimus was done clinically by surveillance for incidence of any complications e.g chest infections, diarrhoea, mucositis. and laboratory assessment after 2 weeks and after every 6 months including blood picture, liver function test (Alanine transferase) , kidney function test (creatinine), fasting lipid profile :cholesterol and triglycerides and sirolimus trough level. RESULTS: 33patients were enrolled, Age of the patient during start of sirolimus ranged from 5 months to 13 years with median age 3 years. Bleeding stopped in 15 patients (93.8%), cosmetic Disfigurement improved in 21 patients (80%) and perception of pain improved in 8 patients (72.7%). Also, mean pediatric quality of life score rase from 65.18 to 78 after sirolimus. 10 (30%)patients had adverse effects from sirolimus including infections 15.2% ,,mucositis 12.1% and diarrhea 1%. CONCLUSIONS: Patients with complex vascular malformation require multidisciplinary team for diagnosis and management. Symptomatic relief in patients after sirolimus is evident with better quality of life.