{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T09:01:08Z","timestamp":1792918868208,"version":"4.5.0"},"reference-count":37,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,7]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent \u03b2-thalassemia (TDT) involves autologous transplantation of hematopoietic stem and progenitor cells transduced with a modified \u03b2-globin gene to produce functional adult hemoglobin (Hb) containing \u03b2A-T87Q-globin (HbAT87Q). Sixty-three participants with TDT (median age, 17 years [range, 4-35]) received beti-cel in phase 1\/2 (n = 22) or phase 3 (n = 41) studies and enrolled in the long-term follow-up LTF-303 study (median follow-up, 5.9 years [range, 2.9-10.1]). Manufacturing refinements in phase 3 increased transduction efficiency, resulting in higher drug product vector copy number and HbAT87Q levels, which translated into higher Hb and transfusion independence (TI) rates than in phase 1\/2. TI was achieved by 15 of 22 (68.2%) phase 1\/2 participants (median weighted average Hb during TI, 10.2 g\/dL) and 37 of 41 (90.2%) of phase 3 participants (median, 11.2 g\/dL), and was sustained through last follow-up. Treatment efficacy was similar across ages and TDT genotypes. Among participants achieving TI, 38 of 52 (73%) had discontinued iron chelation at last follow-up, with no increase in liver iron concentration. Markers of ineffective erythropoiesis, including serum transferrin receptor and erythropoietin, improved with restoration of iron homeostasis. Health-related quality-of-life assessment scores showed durable improvements. No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported. These findings establish beti-cel as a durable, 1-time therapy that achieves TI, restores iron balance, and improves quality of life, offering a potentially curative treatment option for people with TDT. This trial was registered at www.clinicaltrials.gov as NCT02633943.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029196","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T20:01:36Z","timestamp":1768248096000},"page":"2203-2214","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":14,"title":["Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent \u03b2-thalassemia"],"prefix":"10.1182","volume":"147","author":[{"given":"Janet L.","family":"Kwiatkowski","sequence":"first","affiliation":[{"name":"1Division of Hematology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"},{"name":"2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4961-8103","authenticated-orcid":false,"given":"Alexis A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"},{"name":"2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1851-7521","authenticated-orcid":false,"given":"Jennifer","family":"Schneiderman","sequence":"additional","affiliation":[{"name":"3Division of Hematology Oncology NeuroOncology and Stem Cell Transplantation, Ann & Robert H. 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