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• W4387245660 abstract "Abstract Luspatercept, a ligand‐trapping fusion protein, binds select TGF‐β superfamily ligands implicated in thalassemic erythropoiesis, promoting late‐stage erythroid maturation. Luspatercept reduced transfusion burden in the BELIEVE trial (NCT02604433) of 336 adults with transfusion‐dependent thalassemia (TDT). Analysis of biomarkers in BELIEVE offers novel physiological and clinical insights into benefits offered by luspatercept. Transfusion iron loading rates decreased 20% by 1.4 g (~7 blood units; median iron loading rate difference: −0.05 ± 0.07 mg Fe/kg/day, p < .0001) and serum ferritin (s‐ferritin) decreased 19.2% by 269.3 ± 963.7 μg/L ( p < .0001), indicating reduced macrophage iron. However, liver iron content (LIC) did not decrease but showed statistically nonsignificant increases from 5.3 to 6.7 mg/g dw. Erythropoietin, growth differentiation factor 15, soluble transferrin receptor 1 (sTfR1), and reticulocytes rose by 93%, 59%, 66%, and 112%, respectively; accordingly, erythroferrone increased by 51% and hepcidin decreased by 53% (all p < .0001). Decreased transfusion with luspatercept in patients with TDT was associated with increased erythropoietic markers and decreasing hepcidin. Furthermore, s‐ferritin reduction associated with increased erythroid iron incorporation (marked by sTfR1) allowed increased erythrocyte marrow output, consequently reducing transfusion needs and enhancing rerouting of hemolysis (heme) iron and non‐transferrin‐bound iron to the liver. LIC increased in patients with intact spleens, consistent with iron redistribution given the hepcidin reduction. Thus, erythropoietic and hepcidin changes with luspatercept in TDT lower transfusion dependency and may redistribute iron from macrophages to hepatocytes, necessitating the use of concomitant chelator cover for effective iron management." @default.
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• W4387245660 date "2023-10-02" @default.
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• W4387245660 title "Luspatercept stimulates erythropoiesis, increases iron utilization, and redistributes body iron in transfusion‐dependent thalassemia" @default.
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• W4387245660 doi "https://doi.org/10.1002/ajh.27102" @default.
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