{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:43:31Z","timestamp":1792763011883,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Exagamglogene autotemcel (exa\u2010cel) is a one\u2010time, ex\u00a0vivo, CRISPR\u2010Cas9 gene edited cell therapy approved for patients with transfusion dependent \u03b2\u2010thalassemia (TDT) aged 12\u201335\u2009years. In a Phase 3 study (CLIMB THAL\u2010111), exa\u2010cel treatment resulted in reactivation of fetal hemoglobin and increases in total hemoglobin, leading to transfusion independence in 91% of participants. Here, we report on the impact of exa\u2010cel treatment on measures of ineffective erythropoiesis and iron homeostasis, which were secondary and exploratory endpoints in CLIMB THAL\u2010111 and the CLIMB\u2010131 long\u2010term follow\u2010up study. Prior to exa\u2010cel infusion, all participants were receiving regular red blood cell transfusions and iron chelation therapy. At time of data cut (April 2025), 98% of participants (55 of 56) had been transfusion independent for \u2265\u200912\u2009months and 38 (68%) had discontinued iron removal therapy (mean duration off iron removal therapy 19.4\u2009months). Following transfusion independence and cessation of iron removal therapy, erythroferrone concentrations decreased and hepcidin levels normalized in all participants, indicating correction of ineffective erythropoiesis and restoration of iron homeostasis. Further supporting this finding, improvements and trends toward normalization were seen in key erythropoiesis biomarkers, including erythropoietin levels, reticulocyte counts, and soluble transferrin receptor concentrations. Iron overload biomarkers, including ferritin, liver iron concentration, and cardiac T2*, decreased and then remained stable throughout follow\u2010up, even after cessation of iron removal therapy. These results demonstrate restoration of effective erythropoiesis and iron homeostasis after exa\u2010cel infusion in the setting of transfusion independence following reactivation of fetal hemoglobin. (CLIMB THAL\u2010111 and CLIMB\u2010131; Clinical Trials.gov numbers NCT03655678 and NCT04208529).<\/jats:p>","DOI":"10.1002\/ajh.70382","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:46:31Z","timestamp":1780897591000},"page":"1969-1979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Correction of Ineffective Erythropoiesis and Normalization of Iron Homeostasis After Exagamglogene Autotemcel in Transfusion\u2010Dependent \u03b2\u2010Thalassemia"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-1244","authenticated-orcid":false,"given":"Sujit","family":"Sheth","sequence":"first","affiliation":[{"name":"Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selim","family":"Corbacioglu","sequence":"additional","affiliation":[{"name":"University of Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josu","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Imperial College Healthcare NHS Trust, St Mary's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Algeri","sequence":"additional","affiliation":[{"name":"IRCCS, Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"},{"name":"Department of Health Sciences Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Rupprecht","sequence":"additional","affiliation":[{"name":"University Children's Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin H. M.","family":"Kuo","sequence":"additional","affiliation":[{"name":"University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Stanford University  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lang","sequence":"additional","affiliation":[{"name":"University of T\u00fcbingen, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Merkeley","sequence":"additional","affiliation":[{"name":"The University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Carpenter","sequence":"additional","affiliation":[{"name":"University College London Hospitals NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus Y.","family":"Mapara","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert I.","family":"Liem","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. Lurie Children's Hospital of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Grupp","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9891-6759","authenticated-orcid":false,"given":"Yogi","family":"Chopra","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children\/University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Li","sequence":"additional","affiliation":[{"name":"BC Children's Hospital, University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Kirby\u2010Allen","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children\/University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Domenica","family":"Cappellini","sequence":"additional","affiliation":[{"name":"Ca'granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-0655","authenticated-orcid":false,"given":"Antonis","family":"Kattamis","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakellarios","family":"Zairis","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Liu","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haydar","family":"Frangoul","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at The Children's Hospital at TriStar Centennial  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7976-3654","authenticated-orcid":false,"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"IRCCS, Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"},{"name":"Catholic University of the Sacred Heart  Rome 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