Eltrombopag mobilizes iron in patients with aplastic anemia

Zhao, Zhen; Sun, Qian; Sokoll, Lori J.; Streiff, Michael B.; Cheng, Zhe; Grasmeder, Sophie; Townsley, Danielle M.; Young, Neal S.; Dunbar, Cynthia E.; Winkler, Thomas

doi:10.1182/blood-2018-01-826784

Cited by 32 publications

(29 citation statements)

References 11 publications

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“…It has been identified that the thrombopoietin (TPO) receptor is expressed not only on megakaryocytes, but also on hematopoietic stem cells [2]. So it is easy to understand that eltrombopag (ELT), an oral TPO receptor agonist, which has been first designed for immune thrombocytopenia [3], has been proved to promote tri-lineage hematopoiesis [4] in patients with AA [5,6]. Olnes et al [7] did the first trial of eltrombopag on 25 patients with refractory AA, and found that 11 of them had at least one lineage response at 12 weeks' treatment.…”

Section: Introductionmentioning

confidence: 99%

Eltrombopag is effective in patients with relapse/refractory aplastic anemia—report from a single center in China

et al. 2020

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Eltrombopag has shown a promising effect on patients with refractory/relapsed aplastic anemia (AA). However, data in Asian patients are limited due to the short launching time. Data from relapsed/refractory AA patients treated with eltrombopag in Peking Union Medical College Hospital from December 2017 to May 2019 were analyzed retrospectively. Totally 41 patients including 37 non-severe AA and 4 severe AA were analyzed with a median age of 47 (13~81) years old. The dosage of eltrombopag varies from 25 mg every other day (qod) to 100 mg every day (qd) (median 75 mg qd) with the duration of 13 (3~23) months. The overall response rates were 51.2%, 58.5%, and 55.2% at 3-month, 6-month, and 1-year follow-up. Seventy-five percent of patients achieved the best response below the dosage of 75 mg qd at 3 (1–6) months. Two patients stopped eltrombopag after achieving complete remission and remained stable. Two patients relapsed and evolved to myelodysplastic syndrome. Adverse events included gastrointestinal discomfort, hepatic toxicity, and skin reactions, which were mild and controllable. Eltrombopag is effective for Chinese relapsed/refractory AA patients with a relatively lower dose and acceptable side effects.

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Section: Introductionmentioning

confidence: 99%

Eltrombopag is effective in patients with relapse/refractory aplastic anemia—report from a single center in China

et al. 2020

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“…48,49 Chelation was also observed in vivo in AA patients treated with eltrombopag. 50 This effect has been proposed to account, in part, for the improved function of cells cultured with eltrombopag, its antiproliferative properties in acute myeloid leukemia 48,51 and hepatocellular carcinoma, 52 and the clinical hematopoietic benefits in subjects with AA [38][39][40] and myelodysplastic syndrome. 53 The iron-mobilizing effects were observed in human and rodent cells.…”

Section: Discussionmentioning

confidence: 99%

Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-γ

Alvarado

Huntsman

Cheng

et al. 2019

Blood

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The proinflammatory cytokine interferon-γ (IFN-γ) has been implicated in human hematopoietic stem and progenitor cell (HSPC) depletion in immune-mediated bone marrow failure syndromes. We show that IFN-γ specifically prevents full engagement of thrombopoietin (TPO), a primary positive regulator of HSPC survival, to its receptor (c-MPL) via steric occlusion of the low-affinity binding site, contributing to perturbation of TPO-induced signaling pathways and decreased survival of human HSPCs. Eltrombopag, a synthetic small molecule mimetic of TPO that interacts with c-MPL at a position distinct from the extracellular binding site of TPO, bypasses this inhibition, providing an explanation for its clinical activity in bone marrow failure, despite already elevated endogenous TPO levels. Thus, IFN-γ–mediated perturbation of TPO:c-MPL complex formation and the resulting inhibition of a critical pathway of growth factor cell signaling may represent a general mechanism by which IFN-γ impairs the function of human HSPCs. This understanding could have broad therapeutic implications for various disorders of chronic inflammation.

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“…In addition, the inhibition of cell division and differentiation by blocking malignant cells in the G1 phase has been observed. As a result, survival was improved in mouse leukemia models [18,19,20]. Punzo et al [21] also showed that EPAG binds to metal ions and especially iron(III).…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children With Immune Thrombocytopenia in Turkey

Yozgat

Leblebisatan

Akbayram

et al. 2020

Tjh

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Objective: Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children. Materials and Methods: The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia. Amaç: İmmün trombositopeni (İTP) nadir otoimmün bir hastalık olup, platelet sayısındaki azalmaya bağlı olarak peteşi, ekimoz, epistaksis gibi kanama semptomları ile karakterizedir. Trombopoietin reseptör agonisti eltrombopag (EPAG), yetişkinlerde ve çocuklarda kronik immün trombositopeni tedavisinde kullanılan ikinci basamak bir ajandır. Gereç ve Yöntemler: Bu retrospektif çalışma, akut refrakter ve kronik immün trombositopenili çocuk hastalarda EPAG tedavisinin etkinliğini, güvenilirliğini, yan etkilerini özellikle de demir eksikliği anemisi gelişimini değerlendirmiştir.

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Eltrombopag mobilizes iron in patients with aplastic anemia

Cited by 32 publications

References 11 publications

Eltrombopag is effective in patients with relapse/refractory aplastic anemia—report from a single center in China

Eltrombopag is effective in patients with relapse/refractory aplastic anemia—report from a single center in China

Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-γ

Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children With Immune Thrombocytopenia in Turkey

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