{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T01:51:06Z","timestamp":1793929866620,"version":"4.8.0"},"reference-count":30,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,3,21]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>High-risk, complement mediated, untreated transplant-associated thrombotic microangiopathy (hrTMA) has dismal outcomes due to multi-organ dysfunction syndrome (MODS). The complement C5 blocker eculizumab shows promising results in hrTMA, but has not been prospectively studied in hematopoietic stem cell transplant (HCT) recipients. We performed the first multi-institutional prospective study in children and young adults to evaluate eculizumab as an early targeted intervention for hrTMA\/MODS. We hypothesized that eculizumab would more than double survival in HCT recipients with hrTMA, compared to our prior study of prospectively screened, untreated hrTMAs serving as historical controls. HrTMA features (elevated terminal complement (sC5b-9) and proteinuria measured by random urine protein\/creatinine ratio (\u22651mg\/mg)) were required for inclusion. The primary endpoint was survival at 6 six-months from hrTMA diagnosis. Secondary endpoints were cumulative incidence of MODS 6 months after hrTMA diagnosis and 1-year posttransplant survival. Eculizumab dosing included intensive loading, induction, and maintenance phases for up to 24 weeks of therapy. All 21 evaluated study subjects had MODS. Primary and secondary study endpoints were met by demonstrating survival of 71% (P &amp;lt; .0001) 6 months after hrTMA diagnosis and 62% 1 year after transplant. Of fifteen survivors, 11 (73%) fully recovered organ function and are well. Our study demonstrates significant improvement in survival and recovery of organ function in hrTMA using an intensified eculizumab dosing and real time biomarker monitoring. This study serves as a benchmark for planning future studies that should focus on preventative measures or targeted therapy to be initiated prior to organ injury. This trial was registered at www.clinicaltrials.gov as #NCT03518203.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023022526","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T04:14:40Z","timestamp":1699589680000},"page":"1112-1123","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":68,"title":["A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation\u2013associated TMA"],"prefix":"10.1182","volume":"143","author":[{"given":"Sonata","family":"Jodele","sequence":"first","affiliation":[{"name":"1Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4001-9203","authenticated-orcid":false,"given":"Christopher E.","family":"Dandoy","sequence":"additional","affiliation":[{"name":"1Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-806X","authenticated-orcid":false,"given":"Paibel","family":"Aguayo-Hiraldo","sequence":"additional","affiliation":[{"name":"3Division of Bone Marrow Transplantation, Children\u2019s Hospital of Los Angeles, Los Angeles, CA"},{"name":"4Keck School of Medicine of University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Lane","sequence":"additional","affiliation":[{"name":"1Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Teusink-Cross","sequence":"additional","affiliation":[{"name":"5Department of Pharmacy, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Sabulski","sequence":"additional","affiliation":[{"name":"1Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Mizuno","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH"},{"name":"6Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Laskin","sequence":"additional","affiliation":[{"name":"7Division of Nephrology, Children\u2019s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-2701","authenticated-orcid":false,"given":"Jason","family":"Freedman","sequence":"additional","affiliation":[{"name":"8Division of Oncology, Children\u2019s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella M.","family":"Davies","sequence":"additional","affiliation":[{"name":"1Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"1","key":"2024032115211552300_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/bloodadvances.2020003455","article-title":"A\u00a0pragmatic multi-institutional approach to understanding transplant-associated thrombotic microangiopathy after stem cell transplant","volume":"5","author":"Dandoy","year":"2021","journal-title":"Blood 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