Adjunct Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Intraluminal Pediatric Pulmonary Vein Stenosis

J Pediatr. 2018 Jul;198:29-35.e5. doi: 10.1016/j.jpeds.2018.01.029. Epub 2018 Mar 23.


Objective: To evaluate the use of imatinib mesylate with or without bevacizumab targeting neoproliferative myofibroblast-like cells with tyrosine kinase receptor expression, as adjuncts to modern interventional therapies for the treatment of multivessel intraluminal pulmonary vein stenosis (PVS). We describe the 48- and 72-week outcomes among patients receiving imatinib mesylate with or without bevacizumab for multivessel intraluminal PVS.

Study design: This single-arm, prospective, open-label US Food and Drug Administration approved trial enrolled patients with ≥2 affected pulmonary veins after surgical or catheter-based relief of obstruction between March 2009 and December 2014. Drug therapy was discontinued at 48 weeks, or after 24 weeks of stabilization, whichever occurred later.

Results: Among 48 enrolled patients, 5 had isolated PVS, 26 congenital heart disease, 5 lung disease, and 12 both. After the 72-week follow-up, 16 patients had stabilized, 27 had recurred locally without stabilization, and 5 had progressed. Stabilization was associated with the absence of lung disease (P = .03), a higher percentage of eligible drug doses received (P = .03), and was not associated with age, diagnosis, disease laterality, or number of veins involved. Survival to 72 weeks was 77% (37 of 48). Adverse events were common (n = 1489 total), but only 16 were definitely related to drug treatment, none of which were serious.

Conclusion: Survival to 72 weeks was 77% in a referral population with multivessel intraluminal PVS undergoing multimodal treatment, including antiproliferative tyrosine kinase blockade. Toxicity specific to tyrosine kinase blockade was minimal.

Keywords: congenital heart disease; drug therapy; outcome; treatment.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Male
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use*
  • Stenosis, Pulmonary Vein / drug therapy*
  • Stenosis, Pulmonary Vein / mortality
  • Treatment Outcome


  • Angiogenesis Inhibitors
  • Protein Kinase Inhibitors
  • Bevacizumab
  • Imatinib Mesylate