title: Sirolimus for the treatment of children with various complicated vascular anomalies.
abstract: Vascular anomalies include a heterogeneous group of disorders that are categorized as vascular tumors or vascular malformations. Treatment options include resection, embolization, laser therapy, and sclerotherapy or medical treatment such as propranolol, steroids, interferon, and cytostatic chemotherapy. Mammalian target of rapamycin seems to play a key role in the signal pathway of angiogenesis and subsequently in the development of vascular anomalies. Recently, the successful use of sirolimus has been reported in children with lymphatic malformations and kaposiform hemangioendotheliomas. We report on six patients with different vascular anomalies (kaposiform hemangioendothelioma n = 2, combined lymphatico-venous malformation n = 2, pulmonary lymphangiectasia n = 1, and orbital lymphatic malformation n = 1) who were treated with peroral sirolimus. Three of the children initially presented with a Kasabach-Merrit phenomenon. Median duration of treatment was 10 months; two children are still on treatment. Three children each achieved complete and partial remission. Kasabach-Merrit phenomenon resolved within 1 month in all patients. Treatment with sirolimus was tolerated well; only mild reversible leukopenia was observed.
  
  
  CONCLUSIONS
  Sirolimus proved to be effective in children with complicated lymphatic or lymphatico-venous malformations and kaposiform hemangioendotheliomas. Treatment was tolerated well with acceptable side effects. The optimum length of treatment and possible long-term side effects have to be evaluated.
  
  
  BACKGROUND
  • Vascular anomalies including vascular tumors and vascular malformations may lead to life-threatening conditions.• Some patients are refractory to established treatment and/or are not available for local invasive procedures.
  
  
  BACKGROUND
  • We reviewed the literature focusing treatment of vascular anomalies inc hildren and adolescents.• Our data support recent studies that sirolimus is an effective treatment option in patients with complicated vascular tumors andmalformations
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. herwig.lackner@medunigraz.at.
authors.forename: Herwig
authors.initials: H
authors.lastname: Lackner
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. a.karastaneva@yahoo.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Karastaneva
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. wolfgang.schwinger@medunigraz.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwinger
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. martin.benesch@medunigraz.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. petra.sovinz@klinikum-graz.at.
authors.forename: Petra
authors.initials: P
authors.lastname: Sovinz
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. markus.seidel@medunigraz.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Seidel
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. daniela.sperl@medunigraz.at.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sperl
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. sofia.lanz@klinikum-graz.at.
authors.forename: Sofia
authors.initials: S
authors.lastname: Lanz
authors.affiliation: Department of Pediatric and Adolescence Surgery, Medical University of Graz, Graz, Austria. emir.haxhija@klinikum-graz.at.
authors.forename: Emir
authors.initials: E
authors.lastname: Haxhija
authors.affiliation: Division of Neonatology, Medical University of Graz, Graz, Austria. friedrich.reiterer@medunigraz.at.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Reiterer
authors.affiliation: Division of Pediatric Radiology, Medical University of Graz, Graz, Austria. erich.sorantin@medunigraz.at.
authors.forename: Erich
authors.initials: E
authors.lastname: Sorantin
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria. christian.urban@medunigraz.at.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Urban
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D054079:Vascular Malformations / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D020123:Sirolimus
keywords: Children; Sirolimus; Treatment; Vascular anomalies