{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:35:18Z","timestamp":1791858918941,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"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. Pharmacol."],"abstract":"<jats:p>Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of hematopoietic stem cell transplantation in which systemic complement activation induces endothelial injury, leading to microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction. TA-TMA often progresses rapidly and has historically been associated with high mortality. Over the last decade, increasing recognition of complement activation as a central driver of TA-TMA has shifted management from largely empirical supportive care toward mechanism-based therapy. This review summarizes recent advances in complement-targeted therapies for TA-TMA and outlines key aspects of pathophysiology, risk factors, and monitoring that inform therapeutic decision-making. Earlier non\u2013complement-directed therapies, including calcineurin inhibitor modification, plasma exchange, defibrotide, and rituximab, showed limited and inconsistent benefit. In contrast, complement-targeted therapies have advanced the treatment of TA-TMA. Prospective and large cohort data support the clinical activity of eculizumab (C5 inhibitor), with meaningful improvements in survival and organ recovery. Ravulizumab (long-acting C5 inhibitor) has shown encouraging phase 3 results, and narsoplimab (MASP-2 inhibitor), which became the first approved treatment for TA-TMA, has demonstrated promising outcomes, including activity in some patients previously exposed to C5 inhibition. In addition, newer agents targeting C5, C3, or factor B are expanding the therapeutic horizon for TA-TMA, although efficacy data are still limited for some of these therapies. Overall, complement-targeted therapies represent a therapeutic advance in TA-TMA, and ongoing prospective studies will be crucial to define optimal agent selection, sequencing, and integration into clinical practice.<\/jats:p>","DOI":"10.3389\/fphar.2026.1835245","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T22:10:25Z","timestamp":1781475025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Complement-targeted therapies for transplant-associated thrombotic microangiopathy: recent advances"],"prefix":"10.3389","volume":"17","author":[{"given":"Taichiro","family":"Tokura","sequence":"first","affiliation":[{"name":"Department of Hematology, Tokyo Metropolitan Tama-Hokubu Medical Center","place":["Tokyo, Japan"]},{"name":"Department of Hematology, Nippon Medical School","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayuri","family":"Motomura","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Metropolitan Tama-Hokubu Medical Center","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1002\/ajh.27651","article-title":"Clinical outcomes and treatment strategies of adult transplant-associated thrombotic microangiopathy: external validation of harmonizing definitions and high-risk criteria","volume":"100","author":"Acosta-Medina","year":"2025","journal-title":"Am. 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