{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T20:08:00Z","timestamp":1787947680672,"version":"build-2784847793"},"reference-count":28,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Aplastic anemia (AA) in its severe form has historically been associated with high mortality. With limited supportive care and no effective strategy to reverse marrow failure, most patients diagnosed with severe AA (SAA) died of pancytopenia complications. Since the 1970s, hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have changed SAA's natural history by improving marrow function and pancytopenia. Standard IST with horse anti-thymocyte globulin plus cyclosporine produces a hematologic response rate of 60 to 70%. In the long term, about one-third of patients relapse, and 10 to 15% can develop cytogenetic abnormalities. Outcomes with either HSCT or IST are similar, and choosing between these modalities relies on age, availability of a histocompatible donor, comorbidities, and patient preference. The introduction of eltrombopag, a thrombopoietin receptor agonist, improved SAA outcomes as both salvage (second-line) and upfront therapy combined with IST. As a single agent, eltrombopag in doses up to 150 mg daily improved cytopenias in 40 to 50% in those who failed initial IST, which associated with higher marrow cellularity, suggesting a pan-stimulatory marrow effect. When eltrombopag was combined with IST as upfront therapy, overall (about 90%) and complete responses (about 50%) were higher than observed extensively with IST alone of 65% and 10%, respectively. Not surprisingly, given the strong correlation between hematologic response rates and survival in SAA, most (&gt;90%) were alive after a median follow-up of 18 months. Longer follow-up and real-word data continue to confirm the activity of this agent in AA. The use of eltrombopag in different combinations and doses are currently being explored. The activity of another thrombopoietin receptor agonist in AA, romiplostim, suggests a class effect. In the coming years, the mechanisms of their activity and the most optimal regimen are likely to be elucidated.<\/ns4:p>","DOI":"10.12688\/f1000research.22214.1","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T13:02:15Z","timestamp":1599742935000},"page":"1118","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Novel therapeutic choices in immune aplastic anemia"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-4538","authenticated-orcid":false,"given":"Phillip","family":"Scheinberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1185-96","DOI":"10.1182\/blood-2011-12-274019","article-title":"How I treat acquired aplastic anemia.","volume":"120","author":"P Scheinberg","year":"2012","journal-title":"Blood."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"97-104","DOI":"10.1182\/hematology.2019000019","article-title":"Idiopathic aplastic anemia vs hypocellular myelodysplastic syndrome.","volume":"2019","author":"J Durrani","year":"2019","journal-title":"Hematology Am Soc Hematol Educ Program."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"609-18","DOI":"10.1016\/j.hoc.2018.03.003","article-title":"Recent Advances and Long-Term Results of Medical Treatment of Acquired Aplastic Anemia: Are Patients Cured?","volume":"32","author":"P Scheinberg","year":"2018","journal-title":"Hematol Oncol Clin North Am."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"2353-65","DOI":"10.1056\/NEJMra0903373","article-title":"Telomere diseases.","volume":"361","author":"R Calado","year":"2009","journal-title":"N Engl J Med."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"1643-56","DOI":"10.1056\/NEJMra1413485","article-title":"Aplastic Anemia.","volume":"379","author":"N Young","year":"2018","journal-title":"N Engl J Med."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1428-36","DOI":"10.1182\/blood-2016-08-693481","article-title":"How I treat acquired aplastic anemia.","volume":"129","author":"A Bacigalupo","year":"2017","journal-title":"Blood."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"1130-5","DOI":"10.1001\/jama.289.9.1130","article-title":"Antithymocyte globulin and cyclosporine for severe aplastic anemia: Association between hematologic response and long-term outcome.","volume":"289","author":"S Rosenfeld","year":"2003","journal-title":"JAMA."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1989-92","DOI":"10.1182\/blood-2017-09-807859","article-title":"Transplant outcome for patients with acquired aplastic anemia over the age of 40: Has the outcome improved?","volume":"131","author":"S Giammarco","year":"2018","journal-title":"Blood."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"585-94","DOI":"10.1111\/bjh.13614","article-title":"Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. 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Gaslini Children's Research Hospital, Genova, Italy, 10 Sep 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-1118\/v1#referee-response-71175","order":0,"name":"referee-response-71175","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.24499.r71174, Maria A. 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