{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:07:13Z","timestamp":1789589233197,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Extensive venous malformations involving limbs severely impact quality of life, mostly due to chronic pain and functional limitations. But patients can also display coagulopathy with associated risks of life\u2010threatening thromboembolism and bleeding. Available pharmacological treatments (e.g., sirolimus) are not universally effective. Novel therapies are urgently needed for patients with treatment\u2010resistant venous malformations. We report three patients with TIE\u20102 receptor mutations treated with alpelisib for 6 months (daily dosing: 50\u00a0mg for children weighing\u00a0&lt;50\u00a0kg and 100\u00a0mg for those\u00a0&gt;50\u00a0kg). Pain was controlled, gait improved, size of the abnormal venous network decreased, and coagulopathy dramatically improved. Drug exposure was highly variable, suggesting that alpelisib dosing should be individualized to patient's characteristics and guided by therapeutic drug monitoring.<\/jats:p>","DOI":"10.1002\/pbc.29897","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T08:59:58Z","timestamp":1658739598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Repurposing alpelisib, an anti\u2010cancer drug, for the treatment of severe TIE2\u2010mutated venous malformations: Preliminary pharmacokinetics and pharmacodynamic data"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2041-9741","authenticated-orcid":false,"given":"Amandine","family":"Remy","sequence":"first","affiliation":[{"name":"General Pediatric Fellowship Program CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-6233","authenticated-orcid":false,"given":"Thai Hoa","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Department of Pediatrics CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Vascular Anomaly Team CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Research Center CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9e","family":"Dubois","sequence":"additional","affiliation":[{"name":"Vascular Anomaly Team CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Research Center CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Radiology CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gavra","sequence":"additional","affiliation":[{"name":"Departement Clinique de M\u00e9decine de Laboratoire Secteur Pharmacologie Clinique Optilab Montr\u00e9al \u2010 CHU Sainte\u2010Justine  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Lapointe","sequence":"additional","affiliation":[{"name":"Vascular Anomaly Team CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle","family":"Winikoff","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Department of Pediatrics CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Vascular Anomaly Team CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-247X","authenticated-orcid":false,"given":"Garcia\u2010Bournissen","family":"Facundo","sequence":"additional","affiliation":[{"name":"Division of Paediatric Clinical Pharmacology Department of Paediatrics Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Th\u00e9or\u00eat","sequence":"additional","affiliation":[{"name":"Research Center CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Departement Clinique de M\u00e9decine de Laboratoire Secteur Pharmacologie Clinique Optilab Montr\u00e9al \u2010 CHU Sainte\u2010Justine  Montreal Canada"},{"name":"Department of Physiology and Pharmacology CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7730-0541","authenticated-orcid":false,"given":"Niina","family":"Kleiber","sequence":"additional","affiliation":[{"name":"Vascular Anomaly Team CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Research Center CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Departement Clinique de M\u00e9decine de Laboratoire Secteur Pharmacologie Clinique Optilab Montr\u00e9al \u2010 CHU Sainte\u2010Justine  Montreal Canada"},{"name":"Department of Physiology and Pharmacology CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pediatrics CHU Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.11.011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt198"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201048854\u20102"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sempedsurg.2020.150967"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.13461"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/moh.0000000000000498"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010015\u20102842\u20104"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.272"},{"key":"e_1_2_7_10_1","unstructured":"Novartis.Managed access 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