DI-007 Sirolimus for the treatment of complicated vascular anomalies in children

Background Vascular anomalies comprise a heterogeneous group of disorders. The presence of D2-40 markers and the Kasabach–Merrit phenomenon (KMP), characterised by thrombocytopenia and consumption coagulopathy, are associated with major morbidity. Purpose To analyse the efficacy and safety of treatment with sirolimus in children with complicated vascular anomalies (CVA). Material and methods This was a retrospective observational study from December 2014 to August 2016. Inclusion criteria: paediatric patients with CVA treated with sirolimus (off-label use). Data collected: epidemiological and clinical characteristics, treatment and evolution. Results 2 boys with CVA received treatment with sirolimus. Case No 1: 14-month-old boy affected by lymphangiomatosis (D2-40 positive) in his right upper extremity. After receiving rehabilitation treatment with poor improvement, sirolimus (0.8 mg/m 2 /12 hours) was initiated. Pharmacokinetic controls showed mean plasma concentration of 13.22 ng/mL (range 6.27–26.19). Deviation from the target range (5–15 ng/mL) was observed due to drug interaction with azithromycin but normal values were achieved by dose adjustment (0.4 mg/m 2 /day) during the concomitance. After 262 days with active treatment, objective clinical improvement in the functionality of the affected limb was achieved. No adverse effects related to treatment were observed. Case No 2: 32-month-old boy diagnosed with unresectable cervical kaposiform haemangioendothelioma presenting with KMP treated with dual antiplatelet therapy (acetylsalicylic acid and ticlopidine). He had previously received vincristine and systemic high dose glucocorticoids therapies. Given the lack of response, treatment with sirolimus (0.8 mg/m 2 /12 hours) was added to antiplatelet therapy. 5 days after starting sirolimus, platelet values were normalised and remained normal during all treatment (388 days), and for 88 days after stopping treatment. Hypertriglyceridaemia was detected, but was resolved by dose reduction (0.8 mg/m 2 /24 hours) without any decrease in effectiveness. Pharmacokinetic controls showed mean plasma concentration of 9.86 ng/mL (range 3.49–17.8) with a dose of 0.8 mg/m 2 /12 hours and 3.73 ng/mL (range 2.9–4.95) with a dose of 0.8 mg/m 2 /24 hours. Conclusion Sirolimus has been shown be an effective therapeutic option for CVA in childhood. It was well tolerated, and adjusting plasma levels allowed minimisation pf adverse effects without compromising effectiveness. Further studies are needed to determine the contribution of mTOR inhibitors in the treatment of childhood vascular anomalies References and/or acknowledgements Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer2011;57:1018–24. No conflict of interest