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Novel therapeutic choices in immune aplastic anemia

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 tr...

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Autor principal: Scheinberg, Phillip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484718/
https://www.ncbi.nlm.nih.gov/pubmed/32953089
http://dx.doi.org/10.12688/f1000research.22214.1
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author Scheinberg, Phillip
author_facet Scheinberg, Phillip
author_sort Scheinberg, Phillip
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description 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 (>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.
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spelling pubmed-74847182020-09-18 Novel therapeutic choices in immune aplastic anemia Scheinberg, Phillip F1000Res Review 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 (>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. F1000 Research Limited 2020-09-10 /pmc/articles/PMC7484718/ /pubmed/32953089 http://dx.doi.org/10.12688/f1000research.22214.1 Text en Copyright: © 2020 Scheinberg P http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Scheinberg, Phillip
Novel therapeutic choices in immune aplastic anemia
title Novel therapeutic choices in immune aplastic anemia
title_full Novel therapeutic choices in immune aplastic anemia
title_fullStr Novel therapeutic choices in immune aplastic anemia
title_full_unstemmed Novel therapeutic choices in immune aplastic anemia
title_short Novel therapeutic choices in immune aplastic anemia
title_sort novel therapeutic choices in immune aplastic anemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484718/
https://www.ncbi.nlm.nih.gov/pubmed/32953089
http://dx.doi.org/10.12688/f1000research.22214.1
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