Usefulness of eltrombopag for treating thrombocytopenia after allogeneic stem cell transplantation

Rivera, Daniel; Bastida, José María; López-Corral, Lucía; Sánchez‐Guijo, Fermín; Cabrero, Mónica; Martín, Antonio Fuertes; Pérez, Estefanía; López-Parra, Miriam; Avendaño, Alejandro; Veiga, A; Baile, Mónica; Arratibel, Nerea; Carrillo, Javier; Vázquez, Lourdes; Caballero, M D; González‐Porras, José Ramón

doi:10.1038/s41409-018-0368-1

Cited by 30 publications

(26 citation statements)

References 13 publications

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“…Due to its effects on platelet counts and hematopoietic stem cells [2], however, the anti-HCMV effects of eltrombopag are primarily of relevance for anemia patients at risk of HCMV disease, for whom eltrombopag is indicated. Eltrombopag has been suggested for the treatment of cytopenias after hematopoietic stem cell transplantations and case reports support its safety and efficacy [4][5][6][7][8][9]. Since HCMV reactivation and HCMV-associated diseases are leading reasons for the failure of hematopoietic stem cell transplantations [10][11][12], antiviral effects exerted by eltrombopag may also contribute to improved therapy outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Eltrombopag is a thrombopoietin receptor (also known as c-Mpl or MPL) agonist that is used for the treatment of thrombocytopenia, including hepatitis C virus-associated thrombocytopenia [1][2][3]. Its use has also been suggested for the treatment of cytopenias after hematopoietic stem cell transplantations and case reports support its safety and efficacy [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation

Vogel

Schmidt

et al. 2019

Cells

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The thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to the effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interfered with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and the addition of Fe3+ prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after hematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses, and synergistically increase the effects of ganciclovir, eltrombopag is also a drug-repurposing candidate for the treatment of therapy-refractory HCMV disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation

Vogel

Schmidt

et al. 2019

Cells

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“…Eltrombopag has been suggested for the treatment of cytopenias after haematopoietic stem cell transplantations and case reports support its safety and efficacy [4-9]. Since HCMV reactivation and HCMV-associated disease are leading reasons for the failure of haematopoietic stem cell transplantations [10-12], antiviral effects exerted by eltrombopag may also contribute to improved therapy outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Eltrombopag is a thrombopoietin receptor (also known as c-Mpl or MPL) agonist that is used for the treatment of thrombocytopenia [1-3]. Its use has also been suggested for the treatment of cytopenias after haematopoietic stem cell transplantations and case reports support its safety and efficacy [4-9].…”

Section: Introductionmentioning

confidence: 99%

The thrombopoietin receptor agonist eltrombopag inhibits human cytomegalovirus replication via iron chelation

Vogel

Schmidt

et al. 2019

Preprint

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m.michaelis@kent.ac.uk (MM) 18 19 Acknowledgements 20 The work was supported by the Hilfe für krebskranke Kinder Frankfurt e.V. and the 21 Frankfurter Stiftung für krebskranke Kinder. 22 23 2 Abstract 24 The thrombopoietin receptor agonist eltrombopag was successfully used 25 against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to 26 immunomodulatory and antiviral drugs. These effects were ascribed to effects of 27 eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also 28 exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV 29 replication in human fibroblasts and adult mesenchymal stem cells infected with six 30 different virus strains and drug-resistant clinical isolates. Eltrombopag also 31 synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. 32 Time-of-addition experiments suggested that eltrombopag interferes with HCMV 33 replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-34 negative cells, and addition of Fe 3+ prevented the anti-HCMV effects, indicating that it 35 inhibits HCMV replication via iron chelation. This may be of particular interest for the 36 treatment of cytopenias after haematopoietic stem cell transplantation, as HCMV 37 reactivation is a major reason for transplantation failure. Since therapeutic 38 eltrombopag concentrations are effective against drug-resistant viruses and 39 synergistically increase the effects of ganciclovir, eltrombopag is also a drug 40 repurposing candidate for the treatment of therapy-refractory HCMV disease. 41 42 Key words: human cytomegalovirus, antiviral therapy, eltrombopag, thrombopietin 43 receptor agonist, drug resistance, iron chelation 44 45 46

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“…For example, some studies defined response by freedom from platelet transfusion, 34 others by normalization of platelet count, [35][36][37] and others by a target platelet threshold of ≥50 000/µL. [38][39][40][41][42][43][44][45] The best approximation of the combined overall response rate for both agents was 71% (Figure 1).…”

Section: Clinical Studies Of Tro Mimetics After Allogeneic Hctmentioning

confidence: 99%

Use of thrombopoietin receptor agonists after hematopoietic progenitor cell transplantation

Singer

William

2020

Adv. Cell Gene Ther.

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Hematopoietic stem cell transplant (HCT) is used with increasing frequency for the treatment of malignant and nonmalignant diseases. Thrombocytopenia is a common complication following HCT and is associated with decreased survival. Supportive care with platelet transfusion requires significant resources, reduces quality of life, and is associated with several adverse effects including transfusion reaction, infection, and alloimmunization. Thrombopoeitin receptor agonists (TPO-RA) have been found to be safe and effective for the treatment of immune mediated thrombocytopenia, thrombocytopenia related to bone marrow failure syndromes, and thrombocytopenia of chronic liver disease. We hereby discuss in this review the evidence for use of TPO-RA for the management of thrombocytopenia after HCT.

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Usefulness of eltrombopag for treating thrombocytopenia after allogeneic stem cell transplantation

Cited by 30 publications

References 13 publications

The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation

The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation

The thrombopoietin receptor agonist eltrombopag inhibits human cytomegalovirus replication via iron chelation

Use of thrombopoietin receptor agonists after hematopoietic progenitor cell transplantation

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