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Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis.
Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, Davies MV, Alexander MJ, Devine M, Loveday KS, Underwood KW, Grinberg AV, Quisel JD, Chopra R, Pearsall RS, Seehra J, Kumar R. Suragani RN, et al. Nat Med. 2014 Apr;20(4):408-14. doi: 10.1038/nm.3512. Epub 2014 Mar 23. Nat Med. 2014. PMID: 24658078
Cotreatment with ACE-536 and EPO produced a synergistic erythropoietic response. ACE-536 bound growth differentiation factor-11 (GDF11) and potently inhibited GDF11-mediated Smad2/3 signaling. ...
Cotreatment with ACE-536 and EPO produced a synergistic erythropoietic response. ACE-536 bound growth differenti …
Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.
Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Götze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellström-Lindberg E, Zeidan AM, Adès L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Fenaux P, et al. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892. N Engl J Med. 2020. PMID: 31914241 Clinical Trial.
Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). ...The most common luspatercept-associated adverse events (of any grade) included fatigue, …
Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of …
How we manage adults with myelodysplastic syndrome.
Fenaux P, Platzbecker U, Ades L. Fenaux P, et al. Br J Haematol. 2020 Jun;189(6):1016-1027. doi: 10.1111/bjh.16206. Epub 2019 Sep 30. Br J Haematol. 2020. PMID: 31568568 Review.
In LR-MDS without deletion 5q, anaemia is generally treated first by erythropoietic stimulating factors, while second line treatments are currently not approved [lenalidomide, hypomethylating agents (HMA), luspatercept] or rarely indicated (antithymocyte globulin). Lenalid …
In LR-MDS without deletion 5q, anaemia is generally treated first by erythropoietic stimulating factors, while second line treatments are cu …
Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis.
Fenaux P, Kiladjian JJ, Platzbecker U. Fenaux P, et al. Blood. 2019 Feb 21;133(8):790-794. doi: 10.1182/blood-2018-11-876888. Epub 2019 Jan 2. Blood. 2019. PMID: 30602619 Review.
The transforming growth factor-beta superfamily, including activins and growth differentiation factors (GDFs), is aberrantly expressed in lower-risk MDSs and PMF. Luspatercept (and sotatercept), ligand traps that particularly inhibit GDF11, lead to RBC transfusion independ …
The transforming growth factor-beta superfamily, including activins and growth differentiation factors (GDFs), is aberrantly expressed in lo …
Novel therapies in low- and high-risk myelodysplastic syndrome.
Germing U, Schroeder T, Kaivers J, Kündgen A, Kobbe G, Gattermann N. Germing U, et al. Expert Rev Hematol. 2019 Oct;12(10):893-908. doi: 10.1080/17474086.2019.1647778. Epub 2019 Jul 31. Expert Rev Hematol. 2019. PMID: 31353975 Review.
Expert opinion: New therapeutic options for lower-risk patients include thrombopoietin analogues, the TGF-beta family ligand trapping drug Luspatercept, and the telomerase inhibitor Imetelstat. Combinations of hypomethylating agents (HMA) with other compounds, and inhibito …
Expert opinion: New therapeutic options for lower-risk patients include thrombopoietin analogues, the TGF-beta family ligand trapping drug …
Myelodysplastic syndromes: moving towards personalized management.
Hellström-Lindberg E, Tobiasson M, Greenberg P. Hellström-Lindberg E, et al. Haematologica. 2020 Jul;105(7):1765-1779. doi: 10.3324/haematol.2020.248955. Epub 2020 May 21. Haematologica. 2020. PMID: 32439724 Free PMC article. Review.
Agents that stimulate erythropoiesis continue to be first-line treatment for the anemia of lower-risk MDS but luspatercept has shown promise as second-line therapy for sideroblastic MDS and lenalidomide is an established second-line treatment for del(5q) lower-risk MDS. .. …
Agents that stimulate erythropoiesis continue to be first-line treatment for the anemia of lower-risk MDS but luspatercept has shown …
Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis: "2019 Update on Diagnosis, Risk-stratification, and Management".
Patnaik MM, Tefferi A. Patnaik MM, et al. Am J Hematol. 2019 Apr;94(4):475-488. doi: 10.1002/ajh.25397. Epub 2019 Jan 24. Am J Hematol. 2019. PMID: 30618061 Free PMC article. Review.
TREATMENT: Anemia and iron overload are complications seen in both and are managed similar to lower-risk MDS and MPN. The advent of luspatercept, a first-in-class erythroid maturation agent will tremendously boost the ability to manage anemia. ...
TREATMENT: Anemia and iron overload are complications seen in both and are managed similar to lower-risk MDS and MPN. The advent of luspa
Current and emerging treatment options for autoimmune hemolytic anemia.
Barcellini W, Fattizzo B, Zaninoni A. Barcellini W, et al. Expert Rev Clin Immunol. 2018 Oct;14(10):857-872. doi: 10.1080/1744666X.2018.1521722. Epub 2018 Oct 8. Expert Rev Clin Immunol. 2018. PMID: 30204521 Review.
Areas covered: The following targeted therapies are illustrated: drugs acting on CD20 (rituximab, alone or in association with bendamustine and fludarabine) and CD52 (alemtuzumab), B cell receptor and proteasome inhibitors (ibrutinib, bortezomib), complement inhibitors (eculizuma …
Areas covered: The following targeted therapies are illustrated: drugs acting on CD20 (rituximab, alone or in association with bendamustine …
Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia.
Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Piga A, et al. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7. Blood. 2019. PMID: 30617198 Free PMC article. Clinical Trial.
Eighteen non-transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase 1.5 g/dL over 14 days vs baseline. ...In this study, a high percentage of beta-thalassemia patients receiving luspatercept
Eighteen non-transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglo …
A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent beta-Thalassemia.
Cappellini MD, Viprakasit V, Taher AT, Georgiev P, Kuo KHM, Coates T, Voskaridou E, Liew HK, Pazgal-Kobrowski I, Forni GL, Perrotta S, Khelif A, Lal A, Kattamis A, Vlachaki E, Origa R, Aydinok Y, Bejaoui M, Ho PJ, Chew LP, Bee PC, Lim SM, Lu MY, Tantiworawit A, Ganeva P, Gercheva L, Shah F, Neufeld EJ, Thompson A, Laadem A, Shetty JK, Zou J, Zhang J, Miteva D, Zinger T, Linde PG, Sherman ML, Hermine O, Porter J, Piga A; BELIEVE Investigators. Cappellini MD, et al. N Engl J Med. 2020 Mar 26;382(13):1219-1231. doi: 10.1056/NEJMoa1910182. N Engl J Med. 2020. PMID: 32212518 Clinical Trial.
Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was admini …
Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A …
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