Propranolol as an Alternative Treatment Option for Pediatric Lymphatic Malformation

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  • Ozeki Michio
    Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University
  • Kanda Kaori
    Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University
  • Kawamoto Norio
    Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University
  • Ohnishi Hidenori
    Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University
  • Fujino Akihiro
    Department of Pediatric Surgery, Keio University School of Medicine
  • Hirayama Masahiro
    Department of Pediatrics and Cell Transplantation, Mie University Graduate School of Medicine
  • Kato Zenichiro
    Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University
  • Azuma Eiichi
    Department of Pediatrics and Cell Transplantation, Mie University Graduate School of Medicine
  • Fukao Toshiyuki
    Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University
  • Kondo Naomi
    Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University

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Lymphatic malformation (LM), which was previously termed lymphangioma, is a rare congenital malformation of the lymphatic system and its treatment is still challenging. Propranolol (beta blocker) has been recently developed as a first-line treatment of infantile hemangioma. Our study aimed to assess the effect of propranolol on pediatric LM and the relationship between its effectiveness and vascular endothelial growth factor (VEGF) family members (VEGF-A, C and D). Six Japanese patients with LM (age range: 10 months-19 years old; 2 macrocystic, 2 microcystic and 2 combined type) were enrolled. Oral propranolol was administered at 2 mg/kg/day. The efficacy of propranolol for LM was evaluated by the rate of volume change as calculated from MRI imaging and by symptomatic improvement. In all patients, there were no significant side effects. Patients 3 and 5 were classified as objective responders with tumor volume reduction of 30.6% and 22.9%, respectively, at 24 weeks. Patient 1 showed 8% tumor volume reduction and patient 6 showed symptomatic improvement, hence, both were classified as minimal responders. The other two patients were classified as non-responders. Plasma VEGF-A, C, and D levels were significantly higher in the LM group than in the controls (all P < 0.01 by Mann-Whitney test). VEGF-A and D levels at 24 weeks were significantly lower than those at pre-treatment (P = 0.031, 0.047 by Wilcoxon matched pairs test). Though further trials with this treatment must be carried out, we propose that propranolol may be an alternative therapy option for intractable LM.

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