Study protocol and treatment.
toxicity, toxicities
Sirolimus was started at a dose of 0.8 mg/mFluctuating sirolimus levels can be observed in very young patients (<6 months old), requiring frequent dose adaptations, mainly during the first weeks of treatment (Grade 3–4 toxicities required an interruption of the treatment until recovery to grade 1 or higher; sirolimus could subsequently be reintroduced at the initial dose or lower dose, depending on toxicity type, grade, and patient’s preference. Biological tests (including D-dimer and fibrinogen levels) were controlled at baseline, after 1 month, and then every 6 months. Magnetic resonance imaging (MRI) (T1-weighted without gadolinium chelate injection, T2-weighted with Fat Saturation or STIR sequences in 2 orthogonal planes) was performed at baseline and then every 12 months.Sirolimus was administered for a planned treatment duration of 2 years, with a further follow-up of 5 years and frequent visits (every 3 months for the first year and then every 6 months). Sirolimus was allowed to be reintroduced for an undefined duration in case of symptomatic relapse. Treatment was suspended in case of grade 3–4 toxicity related to medication, patient and/or parents who refused to continue, and patients who did not continue their follow-up.