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Sirolimus for the treatment of children with various complicated vascular anomalies

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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.

Conclusion: 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.

What is Known:

• 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.

What is New:

• We reviewed the literature focusing treatment of vascular anomalies in children and adolescents.

• Our data support recent studies that sirolimus is an effective treatment option in patients with complicated vascular tumors and malformations.

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Abbreviations

CT:

Computed tomography

FDA:

Food and Drug Administration

IH:

Infantile hemangioma

ISSVA:

International Society for the Study of Vascular Anomalies

KHE:

Kaposiform hemangioendothelioma

KMP:

Kasabach-Merrit phenomenon

MRI:

Magnetic resonance imaging

mTOR:

Mammalian target of rapamycin

VEGF:

Vascular endothelial growth factor

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Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in our retrospective report were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Author’s contributions

HL and AK prepared the manuscript and searched the literature. DS, WS, MB, PS, MS, DFR, ES, EH and CU revised the manuscript. All authors contributed in the clinical management of the patients and reviewed the manuscript.

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Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Medical University of Graz, Graz, Austria

    Herwig Lackner, Anna Karastaneva, Wolfgang Schwinger, Martin Benesch, Petra Sovinz, Markus Seidel, Daniela Sperl, Sofia Lanz & Christian E. Urban

  2. Department of Pediatric and Adolescence Surgery, Medical University of Graz, Graz, Austria

    Emir Haxhija

  3. Division of Neonatology, Medical University of Graz, Graz, Austria

    Friedrich Reiterer

  4. Division of Pediatric Radiology, Medical University of Graz, Graz, Austria

    Erich Sorantin

Authors
  1. Herwig Lackner
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  2. Anna Karastaneva
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  3. Wolfgang Schwinger
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  4. Martin Benesch
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  5. Petra Sovinz
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  6. Markus Seidel
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  7. Daniela Sperl
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  8. Sofia Lanz
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  9. Emir Haxhija
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  10. Friedrich Reiterer
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  11. Erich Sorantin
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  12. Christian E. Urban
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Corresponding author

Correspondence to Daniela Sperl.

Additional information

Communicated by David Nadal

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Lackner, H., Karastaneva, A., Schwinger, W. et al. Sirolimus for the treatment of children with various complicated vascular anomalies. Eur J Pediatr 174, 1579–1584 (2015). https://doi.org/10.1007/s00431-015-2572-y

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  • DOI: https://doi.org/10.1007/s00431-015-2572-y

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