{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:55:51Z","timestamp":1791384951101,"version":"4.3.3"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel\u2013Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large\u2010scale randomized clinical drug trials challenging. Identification of\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      (phosphatidylinositol\u20104,5\u2010bisphosphate 3\u2010kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010nine patients with CLVM, including KTS and CLOVES, were included. Ninety\u2010three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D\u2010dimer (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.008) and increases in mean fibrinogen (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers\/stomatitis. No toxicities were life\u2010threatening, and none required long\u2010term discontinuation of sirolimus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment\u2010related toxicities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.30215","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T08:30:29Z","timestamp":1674030629000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology, quality of life, and radiographic response"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-5511","authenticated-orcid":false,"given":"Elissa R.","family":"Engel","sequence":"first","affiliation":[{"name":"Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-4924","authenticated-orcid":false,"given":"Adrienne","family":"Hammill","sequence":"additional","affiliation":[{"name":"Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center and Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Adams","sequence":"additional","affiliation":[{"name":"Division of Oncology, Comprehensive Vascular Anomalies Program Children's Hospital of Philadelphia and Perelman School of Medicine and the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderic J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Monash University Royal Children's Hospital  Melbourne New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-8484","authenticated-orcid":false,"given":"Michael","family":"Jeng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha M.","family":"Tollefson","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Pediatrics Mayo Clinic and Mayo Clinic Children's Center  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionela","family":"Iacobas","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\u2010Oncology Texas Children's Hospital  Houston Texas 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School of Medicine San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nibal","family":"Zaghloul","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology The Children's Hospital at Saint Peter's University Hospital  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Drolet","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Pediatrics Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Geddis","sequence":"additional","affiliation":[{"name":"Cancer and Blood Disorders Center Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dov","family":"Goldenberg","sequence":"additional","affiliation":[{"name":"Divisions of Plastic Surgery and General Surgery, Hospital das Clinicas University of Sao Paulo Medical School  Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7253-5632","authenticated-orcid":false,"given":"Kiersten","family":"Ricci","sequence":"additional","affiliation":[{"name":"Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center and Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-3673"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.006"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2014.12.069"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-3257"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2300"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23124"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-015-2572-y"},{"key":"e_1_2_8_9_1","unstructured":"Common Terminology Criteria for Adverse Events v3.0 (CTCAE).NIH; published August 9 2006. 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