Effective low–dose sirolimus regimen for kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon in young infants. Issue 6 (18th January 2022)

• Record Type: Journal Article
• Authors: Harbers, Veroniek E. M.; van der Salm, Nathalie; Pegge, Sjoert A. H.; van der Vleuten, Carine J. M.; Verhoeven, Bas H.; Vrancken, Sabine L. A. G.; Schultze Kool, Leo J.; Fuijkschot, Joris; te Loo, D. Maroeska M. W. M.
• Other Names: Mifsud Janet guestEditor.; Cranswick Noel guestEditor.
• Is Part Of: British journal of clinical pharmacology. Volume 88:Issue 6(2022)
• Page Start: 2769
• Page End: 2781
• Publication Date: 2022-01-18
• Subjects: kaposiform haemangioendothelioma -- Kasabach–Merritt phenomenon -- sirolimus -- vascular tumour; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.15202
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : Aims: Management of kaposiform haemangioendotheliomas (KHE) with Kasabach–Merritt phenomenon is challenging in young infants who are subjected to developmental pharmacokinetic changes. Sirolimus, sometimes combined with corticosteroids, can be used as an effective treatment of KHE. Simultaneously, toxicities such as interstitial pneumonitis related to the use of sirolimus may be fatal. As infants have a very low CYP3‐enzyme expression at birth, which rises during ageing, we hypothesize that a reduced metabolization of sirolimus might lead to high sirolimus serum levels and low dose may be sufficient without the side effects. Methods: A case series of 5 infants with kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon was analysed retrospectively. All infants were treated with sirolimus 0.2 mg/m 2 every 24 or 48 hours according to their age. Prednisone was added to the therapy for additional effect in 4 patients. Results: In all patients, low dose of sirolimus led to therapeutic sirolimus levels (4–6 ng/mL). All infants (aged 4 days–7 months) had a complete haematological response, without serious adverse events. In all patients, the Kasabach–Merritt phenomenon resolved, the coagulation profile normalized and tumour size reduction was seen. Conclusion: Low‐dose sirolimus treatment is safe for infants with kaposiform haemangioendothelioma and Kasabach–Merritt phenomenon. It is essential to realize that during the first months of life, metabolism is still developing and enzymes necessary to metabolise drugs like sirolimus still have to mature. To avoid toxic levels, the sirolimus dosage should be based on age and the associated pharmacological developments.