{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T20:13:12Z","timestamp":1794255192499,"version":"4.9.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation (HSCT), characterized by microangiopathic hemolytic anemia, thrombocytopenia, microthrombosis, and multi-organ dysfunction. Mortality rates range from 50% to 90%, with higher rates observed in high-risk patients. The pathogenesis of TA-TMA involves abnormal activation of the complement system\u2014particularly of the alternative pathway\u2014resulting in endothelial injury and microthrombosis. We present the case of a 17-year-old man with high-risk TA-TMA who achieved a favorable outcome following the oral administration of the factor B inhibitor iptacopan. The patient exhibited significant improvements in laboratory markers, including reductions in lactate dehydrogenase, urine protein\/creatinine ratio, and C5b-9 levels, along with recovery of platelet counts and haptoglobin levels. This case highlights the potential efficacy of iptacopan in the management of TA-TMA, particularly in high-risk patients, and suggests that complement factor B inhibition may offer a promising therapeutic strategy for this challenging condition.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1583506","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T04:15:39Z","timestamp":1755058539000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Successful treatment of transplant-associated thrombotic microangiopathy with iptacopan: a non-adult case study"],"prefix":"10.3389","volume":"16","author":[{"given":"Shijie","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huamin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.blre.2014.11.001","article-title":"A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury","volume":"29","author":"Jodele","year":"","journal-title":"Blood Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1177\/1076029615598221","article-title":"Hematopoietic stem cell transplant-associated thrombotic microangiopathy","volume":"22","author":"Elsallabi","year":"2016","journal-title":"Clin Appl Thromb Hemost"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.08.016","article-title":"Therapeutic Plasma Exchange does not Improve Renal Function in Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy: An Institutional Experience","volume":"25","author":"Sartain","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00133","article-title":"Transplant-associated thrombotic microangiopathy in pediatric hematopoietic cell transplant recipients: A practical approach to diagnosis and management","volume":"7","author":"Dvorak","year":"2019","journal-title":"Front Pediatr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.08.015","article-title":"Prospective clinical and biomarker validation of the american society for transplantation and cellular therapy consensus definition for transplantation-associated thrombotic microangiopathy","volume":"29","author":"Ma","year":"2023","journal-title":"Transpl Cell Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.695037","article-title":"Early elevation of complement factor ba is a predictive biomarker for transplant-associated thrombotic microangiopathy","volume":"12","author":"Okamura","year":"2021","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28070","article-title":"The alternative complement pathway activation product Ba as a marker for transplant-associated thrombotic microangiopathy","volume":"67","author":"Sartain","year":"2019","journal-title":"Pediatr Blood Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13137","article-title":"The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target","volume":"313","author":"Risitano","year":"2023","journal-title":"Immunol Rev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1820892116","article-title":"Small-molecule factor B inhibitor for the treatment of complement-mediated diseases","volume":"116","author":"Schubart","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2018.05.014","article-title":"C3-mediated extravascular hemolysis in PNH on eculizumab: Mechanism and clinical implications","volume":"55","author":"Notaro","year":"2018","journal-title":"Semin Hematol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2201664","article-title":"Breakthrough hemolysis in PNH with proximal or terminal complement inhibition","volume":"387","author":"Notaro","year":"2022","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/bjh.17753","article-title":"How we(\u2018ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future","volume":"196","author":"Risitano","year":"2022","journal-title":"Br J Haematol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.molimm.2018.06.008","article-title":"Developments in anti-complement therapy; from disease to clinical trial","volume":"102","author":"Harris","year":"2018","journal-title":"Mol Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-189944","article-title":"Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab","volume":"113","author":"Risitano","year":"2009","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-625871","article-title":"Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria","volume":"126","author":"Lin","year":"2015","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022006960","article-title":"Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study","volume":"6","author":"Jang","year":"2022","journal-title":"Blood Adv"},{"key":"B17","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1056\/NEJMoa2308695","article-title":"Oral iptacopan monotherapy in paroxysmal nocturnal hemoglobinuria","volume":"390","author":"Peffault de Latour","year":"2024","journal-title":"N Engl J Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1583506\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T04:15:40Z","timestamp":1755058540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1583506\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":17,"alternative-id":["10.3389\/fimmu.2025.1583506"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1583506","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"article-number":"1583506"}}