{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:48:46Z","timestamp":1790380126837,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:00:00Z","timestamp":1676073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Pulmonary vein stenosis results from a proliferative process that leads to the progressive obstruction of venous return to the left atrium. It is often resistant to catheterization and surgical based interventions and is frequently fatal when encountered in its severe form. Here, we describe three patients with severe, primary pulmonary vein stenosis that was progressing despite aggressive conventional management strategies. All three patients were initiated on combination chemotherapy with imatinib and sirolimus, drugs which have been previously shown to independently have potential benefit against PVS. Soon after the initiation of these therapies, all three patients experienced a stabilization of their disease process and clinical improvement. All three patients remain alive, with tolerable side effects from the medications. Although early in our experience and with only a small number of patients, combination chemotherapy with imatinib and sirolimus shows promise and merits further investigation as a therapeutic option for this aggressive disease.<\/jats:p>","DOI":"10.3390\/children10020364","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:28:46Z","timestamp":1676258926000},"page":"364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Combination Chemotherapy in Severe Pulmonary Vein Stenosis\u2014A Case Series"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7454-5957","authenticated-orcid":false,"given":"Gabriel","family":"Krivenko","sequence":"first","affiliation":[{"name":"School of Medicine, University of Central Florida, Orlando, FL 32837, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Iacono","sequence":"additional","affiliation":[{"name":"The Heart Center, Orlando Health Arnold Palmer Hospital for Children, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Nykanen","sequence":"additional","affiliation":[{"name":"The Heart Center, Orlando Health Arnold Palmer Hospital for Children, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Keen","sequence":"additional","affiliation":[{"name":"The Heart Center, Orlando Health Arnold Palmer Hospital for Children, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8617-2337","authenticated-orcid":false,"given":"Robert","family":"Sutphin","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Orlando Health Arnold Palmer Hospital for Children, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Farias","sequence":"additional","affiliation":[{"name":"The Heart Center, Orlando Health Arnold Palmer Hospital for Children, Orlando, FL 32806, USA"},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1161\/CIRCULATIONAHA.106.646166","article-title":"Congenital and acquired pulmonary vein stenosis","volume":"115","author":"Latson","year":"2007","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e656","DOI":"10.1542\/peds.2008-0075","article-title":"Pulmonary vein stenosis: Prematurity and associated conditions","volume":"122","author":"Drossner","year":"2008","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1016\/j.jtcvs.2020.05.117","article-title":"Pulmonary vein stenosis: Treatment and challenges","volume":"161","author":"Vanderlaan","year":"2021","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1016\/j.jcin.2017.05.052","article-title":"Reintervention Is Associated with Improved Survival in Pediatric Patients with Pulmonary Vein Stenosis","volume":"10","author":"Cory","year":"2017","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.athoracsur.2017.03.022","article-title":"Primary Pulmonary Vein Stenosis: Outcomes, Risk Factors, and Severity Score in a Multicentric Study","volume":"104","author":"Kalfa","year":"2017","journal-title":"Ann. Thorac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/ccd.22405","article-title":"Comparison of conventional and cutting balloon angioplasty for congenital and postoperative pulmonary vein stenosis in infants and young children","volume":"75","author":"Peng","year":"2010","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.jtcvs.2015.06.050","article-title":"Outcomes of surgery for young children with multivessel pulmonary vein stenosis","volume":"150","author":"Quinonez","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"747812","DOI":"10.3389\/fped.2021.747812","article-title":"Pulmonary Vein Stenosis: Moving From Past Pessimism to Future Optimism","volume":"9","author":"McLennan","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0002-9149(00)01022-5","article-title":"Mechanism of pulmonary vein stenosis in infants with normally connected veins","volume":"86","author":"Sadr","year":"2000","journal-title":"Am. J. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jpeds.2018.01.029","article-title":"Adjunct Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Intraluminal Pediatric Pulmonary Vein Stenosis","volume":"198","author":"Callahan","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1016\/j.jacc.2021.04.013","article-title":"Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis","volume":"77","author":"Patel","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1111\/j.1747-0803.2011.00574.x","article-title":"A prospective phase II trial of vinblastine and methotrexate in multivessel intraluminal pulmonary vein stenosis in infants and children","volume":"6","author":"Rehman","year":"2011","journal-title":"Congenit. Heart Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1159\/000515816","article-title":"Gleevec and Rapamycin Synergistically Reduce Cell Viability and Inhibit Proliferation and Angiogenic Function of Mouse Bone Marrow-Derived Endothelial Progenitor Cells","volume":"58","author":"Chen","year":"2021","journal-title":"J. Vasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s00246-019-02253-6","article-title":"Systemic Sirolimus to Prevent In-Stent Stenosis in Pediatric Pulmonary Vein Stenosis","volume":"41","author":"Callahan","year":"2020","journal-title":"Pediatr. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.1200\/JCO.2008.21.2514","article-title":"Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: A children\u2019s oncology group study","volume":"27","author":"Schultz","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S1470-2045(12)70377-7","article-title":"Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): A randomised, open-label, intergroup study","volume":"13","author":"Biondi","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1756-8722-5-29","article-title":"Administration of imatinib after allogeneic hematopoietic stem cell transplantation may improve disease-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia","volume":"5","author":"Chen","year":"2012","journal-title":"J. Hematol. Oncol."},{"key":"ref_18","unstructured":"(2021, June 30). UpToDate, Sections on Imatinib, Sirolimus, Sulfamethoxazoletrimethoprim, and Pentamidine. Available online: www.UpToDate.com."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/2\/364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:31:49Z","timestamp":1760121109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/2\/364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,11]]},"references-count":18,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["children10020364"],"URL":"https:\/\/doi.org\/10.3390\/children10020364","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,11]]}}}