{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:09:31Z","timestamp":1792796971821,"version":"4.5.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007642","name":"Universit\u00e0 degli Studi di Roma Tor Vergata","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007642","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Immune thrombocytopenia (ITP) in pediatrics is typically self-limiting, yet a subset develops refractory ITP (rITP), which persists despite standard first-line treatments. Clinical evidence on the efficacy of second-line therapies in this condition, such as mycophenolate mofetil (MMF), rituximab (RTX) and romiplostim, remains limited. This study aims to evaluate the efficacy of second-line therapies for the management of rITP in a cohort of 33 pediatric patients treated at Ospedale Pediatrico Bambino Ges\u00f9 over a 16-year period. Some of these patients switched second-line therapies due to inadequate clinical responses, thus receiving more than one treatment over the study period. Collectively, patients in our cohort received MMF (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920), RTX (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916), romiplostim (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915), dapsone (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093) and sirolimus (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092). Response rates were 50% (10\/20) for mycophenolate mofetil (MMF), 18.8% (3\/16) for rituximab, and 66.7% (10\/15) for romiplostim. None of the 3 patients treated with dapsone showed clinical benefits. One of the two patient undergoing sirolimus achieved a sustained clinical response. Combination therapies showed promising results, particularly the association of MMF and romiplostim. Our results provide new insights into the management of pediatric rITP, while highlighting the need for further studies to establish evidence-based treatment guidelines and improve outcomes of this condition.\n                  <\/jats:p>","DOI":"10.1007\/s00277-025-06542-4","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T06:10:34Z","timestamp":1759471834000},"page":"4981-4985","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Management and outcomes of refractory immune thrombocytopenia in pediatric patients: A retrospective analysis from Ospedale Pediatrico Bambino Ges\u00f9"],"prefix":"10.1007","volume":"104","author":[{"given":"Gabriele","family":"Canciani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cascone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Musolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Torelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Monteferrario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ceglie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"6542_CR1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1002\/ajh.21616","volume":"85","author":"DR Terrell","year":"2010","unstructured":"Terrell DR, Beebe LA, Vesely SK et al (2010) The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol 85:174\u2013180. https:\/\/doi.org\/10.1002\/ajh.21616","journal-title":"Am J Hematol"},{"key":"6542_CR2","doi-asserted-by":"publisher","first-page":"3829","DOI":"10.1182\/bloodadvances.2019000966","volume":"3","author":"C Neunert","year":"2019","unstructured":"Neunert C, Terrell DR, Arnold DM et al (2019) American society of hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 3:3829\u20133866. https:\/\/doi.org\/10.1182\/bloodadvances.2019000966","journal-title":"Blood Adv"},{"key":"6542_CR3","doi-asserted-by":"publisher","first-page":"4190","DOI":"10.1182\/blood-2010-08-302984","volume":"117","author":"C Neunert","year":"2011","unstructured":"Neunert C, Lim W, Crowther M et al (2011) The American society of hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117:4190\u20134207. https:\/\/doi.org\/10.1182\/blood-2010-08-302984","journal-title":"Blood"},{"key":"6542_CR4","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3390\/medicina56120667","volume":"56","author":"DR Terrell","year":"2020","unstructured":"Terrell DR, Neunert CE, Cooper N et al (2020) Immune thrombocytopenia (ITP): current limitations in patient management. Med (Kaunas) 56:667. https:\/\/doi.org\/10.3390\/medicina56120667","journal-title":"Med (Kaunas)"},{"key":"6542_CR5","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1182\/blood-2008-07-162503","volume":"113","author":"F Rodeghiero","year":"2009","unstructured":"Rodeghiero F, Stasi R, Gernsheimer T et al (2009) Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113:2386\u20132393. https:\/\/doi.org\/10.1182\/blood-2008-07-162503","journal-title":"Blood"},{"key":"6542_CR6","doi-asserted-by":"publisher","unstructured":"Russo G, Parodi E, Farruggia P et al (2024) Recommendations for the management of acute immune thrombocytopenia in children. A Consensus Conference from the Italian Association of Pediatric Hematology and Oncology. Blood Transfus 22:253\u2013265. https:\/\/doi.org\/10.2450\/BloodTransfus.501","DOI":"10.2450\/BloodTransfus.501"},{"key":"6542_CR7","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1056\/NEJMra010501","volume":"346","author":"DB Cines","year":"2002","unstructured":"Cines DB, Blanchette VS (2002) Immune thrombocytopenic purpura. N Engl J Med 346:995\u20131008. https:\/\/doi.org\/10.1056\/NEJMra010501","journal-title":"N Engl J Med"},{"key":"6542_CR8","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1002\/ajh.27337","volume":"99","author":"T Pincez","year":"2024","unstructured":"Pincez T, Fernandes H, Fahd M et al (2024) Pediatric refractory chronic immune thrombocytopenia: identification, patients\u2019 characteristics, and outcome. Am J Hematol 99:1269\u20131280. https:\/\/doi.org\/10.1002\/ajh.27337","journal-title":"Am J Hematol"},{"key":"6542_CR9","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1111\/bjh.13622","volume":"171","author":"A Taylor","year":"2015","unstructured":"Taylor A, Neave L, Solanki S et al (2015) Mycophenolate mofetil therapy for severe immune thrombocytopenia. Br J Haematol 171:625\u2013630. https:\/\/doi.org\/10.1111\/bjh.13622","journal-title":"Br J Haematol"},{"key":"6542_CR10","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1111\/bjh.14261","volume":"175","author":"M Miano","year":"2016","unstructured":"Miano M, Ramenghi U, Russo G et al (2016) Mycophenolate mofetil for the treatment of children with immune thrombocytopenia and Evans syndrome. A retrospective data review from the Italian association of paediatric haematology\/oncology. Br J Haematol 175:490\u2013495. https:\/\/doi.org\/10.1111\/bjh.14261","journal-title":"Br J Haematol"},{"key":"6542_CR11","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1097\/MPH.0000000000002688","volume":"45","author":"TA Goldberg","year":"2023","unstructured":"Goldberg TA, Levy CF (2023) Mycophenolate mofetil use in pediatric immune thrombocytopenia refractory to first-line therapy: a single-center experience. J Pediatr Hematol Oncol 45:339\u2013343. https:\/\/doi.org\/10.1097\/MPH.0000000000002688","journal-title":"J Pediatr Hematol Oncol"},{"key":"6542_CR12","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/pbc.23130","volume":"58","author":"RF Grace","year":"2012","unstructured":"Grace RF, Bennett CM, Ritchey AK et al (2012) Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia. Pediatr Blood Cancer 58:221\u2013225. https:\/\/doi.org\/10.1002\/pbc.23130","journal-title":"Pediatr Blood Cancer"},{"key":"6542_CR13","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1111\/bjh.12609","volume":"164","author":"M Pasquet","year":"2014","unstructured":"Pasquet M, Aladjidi N, Guiton C et al (2014) Romiplostim in children with chronic immune thrombocytopenia (ITP): the French experience. Br J Haematol 164:266\u2013271. https:\/\/doi.org\/10.1111\/bjh.12609","journal-title":"Br J Haematol"},{"issue":"2","key":"6542_CR14","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/pbc.25136","volume":"62","author":"JB Bussel","year":"2015","unstructured":"Bussel JB, Hsieh L, Buchanan GR et al (2015) Long-term use of the thrombopoietin-mimetic Romiplostim in children with severe chronic immune thrombocytopenia (ITP). Pediatr Blood Cancer 62(2):208\u2013213. https:\/\/doi.org\/10.1002\/pbc.25136","journal-title":"Pediatr Blood Cancer"},{"key":"6542_CR15","doi-asserted-by":"publisher","first-page":"E175","DOI":"10.1002\/ajh.25119","volume":"93","author":"M Miano","year":"2018","unstructured":"Miano M, Rotulo GA, Palmisani E et al (2018) Sirolimus as a rescue therapy in children with immune thrombocytopenia refractory to mycophenolate mofetil. Am J Hematol 93:E175\u2013E177. https:\/\/doi.org\/10.1002\/ajh.25119","journal-title":"Am J Hematol"},{"issue":"2","key":"6542_CR16","doi-asserted-by":"publisher","DOI":"10.1111\/sji.13376","volume":"100","author":"SO Acar","year":"2024","unstructured":"Acar SO, Tahta N, Al IO et al (2024) Sirolimus is effective and safe in childhood relapsed-refractory autoimmune cytopenias: a multicentre study. Scand J Immunol e13376. https:\/\/doi.org\/10.1111\/sji.13376","journal-title":"Scand J Immunol"},{"key":"6542_CR17","doi-asserted-by":"publisher","first-page":"8338","DOI":"10.4049\/jimmunol.177.12.8338","volume":"177","author":"M Battaglia","year":"2006","unstructured":"Battaglia M, Stabilini A, Migliavacca B et al (2006) Rapamycin promotes expansion of functional CD4\u2009+\u2009CD25\u2009+\u2009FOXP3\u2009+\u2009regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 177:8338\u20138347. https:\/\/doi.org\/10.4049\/jimmunol.177.12.8338","journal-title":"J Immunol"},{"key":"6542_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0916-7","volume":"14","author":"G Stallone","year":"2016","unstructured":"Stallone G, Infante B, Di Lorenzo A et al (2016) mTOR inhibitors effects on regulatory T cells and on dendritic cells. J Transl Med 14:152. https:\/\/doi.org\/10.1186\/s12967-016-0916-7","journal-title":"J Transl Med"},{"key":"6542_CR19","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1111\/jth.12371","volume":"11","author":"C Rodrigo","year":"2013","unstructured":"Rodrigo C, Gooneratne L (2013) Dapsone for primary immune thrombocytopenia in adults and children: an evidence-based review. J Thromb Haemost 11:1946\u20131953. https:\/\/doi.org\/10.1111\/jth.12371","journal-title":"J Thromb Haemost"},{"key":"6542_CR20","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3109\/09537104.2014.886677","volume":"26","author":"AP Patel","year":"2015","unstructured":"Patel AP, Patil AS (2015) Dapsone for immune thrombocytopenic purpura in children and adults. Platelets 26:164\u2013167. https:\/\/doi.org\/10.3109\/09537104.2014.886677","journal-title":"Platelets"},{"key":"6542_CR21","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1111\/j.1600-0609.2005.00545.x","volume":"75","author":"S Damodar","year":"2005","unstructured":"Damodar S, Viswabandya A, George B et al (2005) Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults\u2013a report on 90 patients. Eur J Haematol 75:328\u2013331. https:\/\/doi.org\/10.1111\/j.1600-0609.2005.00545.x","journal-title":"Eur J Haematol"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-025-06542-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-025-06542-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-025-06542-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T20:04:28Z","timestamp":1763409868000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-025-06542-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":21,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["6542"],"URL":"https:\/\/doi.org\/10.1007\/s00277-025-06542-4","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]},"assertion":[{"value":"25 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki. Approval was granted by the Ethics Committee of Bambino Ges\u00f9 Children\u2019s Hospital.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent"}},{"value":"The authors declare no competing interests.\u00a0","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}