Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Efficacy and cost analysis of eltrombopag in thrombocytopenia and poor graft function post allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 56, pages 2471–2476 (2021)Cite this article

Subjects

Abstract

Eltrombopag has shown efficacy in the treatment of thrombocytopenia and poor graft function (PGF) after allogeneic hematopoietic cell transplantation (HCT) in retrospective observational studies, but is not approved for this indication. The cost of this drug is also a major concern in publicly funded health care systems. We collected data about patients who received eltrombopag for thrombocytopenia or PGF after HCT. Post-HCT thrombocytopenia, PGF, and eltrombopag response were defined as per previously published criteria. Primary outcome was treatment efficacy and secondary outcome was cost comparison between estimated treatment cost prior to and after initiation of eltrombopag. Seventeen patients (males 70.6%; median age = 58) received eltrombopag. Isolated thrombocytopenia was present in 11.8% (n = 2) patients while PGF was present in 88.2% (n = 15) of patients. After 8 weeks of treatment at the maximum dose of 150 mg orally daily, overall response rate (ORR) was seen in 76.5% (13/17) of patients: complete response (CR) in 10/13 patients and partial response (PR) in 3/13 patients. The use of eltrombopag was associated with an overall decrease in the total weekly care costs (5021 vs 2,524 CA$; P = 0.04). Thus, Eltrombopag is an efficacious and possibly cost-effective therapy for thrombocytopenia and PGF after allogeneic HCT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Cost Comparison Before and After Initiating Eltrombopag.

Similar content being viewed by others

References

  1. Nash RA, Gooley T, Davis C, Appelbaum FR. The problem of thrombocytopenia after hematopoietic stem cell transplantation. Stem Cells. 1996;14:261–73.

    Article  Google Scholar 

  2. Akahoshi Y, Kanda J, Gomyo A, Hayakawa J, Komiya Y, Harada N, et al. Risk factors and impact of secondary failure of platelet recovery after. Biol Blood Marrow Transplant. 2016;22:1678–83.

    Article  Google Scholar 

  3. Mahat U, Rotz SJ, Hanna R. Use of thrombopoietin receptor agonists in prolonged thrombocytopenia after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2020;26:e65–e73.

    Article  CAS  Google Scholar 

  4. Bruno B, Gooley T, Sullivan KM, Davis C, Bensinger WI, Storb R, et al. Secondary failure of platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7:154–62.

    Article  CAS  Google Scholar 

  5. Lee KH, Lee JH, Choi SJ, Lee JH, Kim S, Seol M, et al. Failure of trilineage blood cell reconstitution after initial neutrophil engraftment in patients undergoing allogeneic hematopoietic cell transplantation-frequency and outcomes. Bone Marrow Transplant. 2004;33:729–34.

    Article  Google Scholar 

  6. Davies SM, Kollman C, Anasetti C, Antin JH, Gajewski J, Casper JT, et al. Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood. 2000;96:4096–102.

    Article  CAS  Google Scholar 

  7. Dominietto A, Raiola AM, van Lint MT, Lamparelli T, Gualandi F, Berisso G, et al. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol. 2001;112:219–27.

    Article  CAS  Google Scholar 

  8. Bolwell B, Pohlman B, Sobecks R, Andresen S, Brown S, Rybicki L, et al. Prognostic importance of the platelet count 100 days post allogeneic bone marrow transplant. Bone Marrow Transplant. 2004;33:419–23.

    Article  CAS  Google Scholar 

  9. First LR, Smith BR, Lipton J, Nathan DG, Parkman R, Rappeport JM. Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes. Blood. 1985;65:368–74.

    Article  CAS  Google Scholar 

  10. Stasia A, Ghiso A, Galaverna F, Raiola AM, Gualandi F, Luchetti S, et al. CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:1440–3.

    Article  CAS  Google Scholar 

  11. Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood. 2007;109:4739–41.

    Article  CAS  Google Scholar 

  12. Imbach P, Crowther M. Thrombopoietin-receptor agonists for primary immune thrombocytopenia. N Engl J Med. 2011;365:734–41.

    Article  CAS  Google Scholar 

  13. Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357:2237–47.

    Article  CAS  Google Scholar 

  14. McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007;357:2227–36.

    Article  CAS  Google Scholar 

  15. Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012;367:11–9.

    Article  CAS  Google Scholar 

  16. Rivera D, Bastida JM, Lopez-Corral L, Sanchez-Guijo F, Cabrero M, Martin A, et al. Usefulness of eltrombopag for treating thrombocytopenia after allogeneic stem cell transplantation. Bone Marrow Transplant. 2019;54:757–61.

    Article  CAS  Google Scholar 

  17. Samarkandi H, Al Nahedh M, Alfattani A, Alsharif F, Bakshi N, Rasheed W, et al. Evaluation of eltrombopag in thrombocytopenia post Hematopoietic cell transplantation: rertrospective observational trial. Hematol Oncol Stem Cell Ther. 2020;30:S1658–3876. https://doi.org/10.1016/j.hemonc.2020.07.006. 30123-0.

    Article  Google Scholar 

  18. Halahleh K, Gale RP, Da’na W, Ma’koseh M, Saadeh S, Alan W, et al. Therapy of posttransplant poor graft function with eltrombopag. Bone Marrow Transplant. 2021;56:4–6.

    Article  Google Scholar 

  19. Fu H, Zhang X, Han T, Mo X, Wang Y, Chen H, et al. Eltrombopag is an effective and safe therapy for refractory thrombocytopenia after haploidentical hematopoietic stem cell transplantation. Bone Marrow Transplant. 2019;54:1310–8.

    Article  CAS  Google Scholar 

  20. Aydin S, Dellacasa C, Manetta S, Giaccone L, Godio L, Iovino G, et al. Rescue treatment with eltrombopag in refractory cytopenias after allogeneic stem cell transplantation. Ther Adv Hematol 2020;11:2040620720961910. https://doi.org/10.1177/2040620720961910.

  21. Blood Component Cost Per Unit Summary—Annual Report. Canadian Blood Services. 2018–2019. https://annual2019.blood.ca/pdfs/CBS-AR2019-en.pdf. Accessed 14 Apr 2021.

  22. Zhang X, Fu H, Xu L, Liu D, Wang J, Liu K, et al. Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes. Biol Blood Marrow Transplant. 2011;17:274–80.

    Article  Google Scholar 

  23. Yamazaki R, Kuwana M, Mori T, Okazaki Y, Kawakami Y, Ikeda Y, et al. Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover. Bone Marrow Transplant. 2006;38:377–84.

    Article  CAS  Google Scholar 

  24. Koike Y, Yoneyama A, Shirai J, Ishida T, Shoda E, Miyazaki K, et al. Evaluation of thrombopoiesis in thrombocytopenic disorders by simultaneous measurement of reticulated platelets of whole blood and serum thrombopoietin concentrations. Thrombosis Haemost. 1998;79:1106–10.

    Article  CAS  Google Scholar 

  25. Vasudevan Nampoothiri R, Kumar R. Eltrombopag: Role in cytopenias following hematopoietic stem cell transplantation. Indian J Hematol Blood Transfus. 2020;36:238–45.

    Article  Google Scholar 

  26. Will B, Kawahara M, Luciano JP, Bruns I, Parekh S, Erickson-Miller CL, et al. Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood. 2009;114:3899.

    Article  CAS  Google Scholar 

  27. Vlachodimitropoulou E, Chen YL, Garbowski M, Koonyosying P, Psaila B, Sola-Visner M, et al. Eltrombopag: a powerful chelator of cellular or extracellular iron(III) alone or combined with a second chelator. Blood. 2017;130:1923–33.

    Article  CAS  Google Scholar 

  28. Alvarado LJ, Huntsman HD, Cheng H, Townsley DM, Winkler T, Feng X, et al. Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-γ. Blood. 2019;133:2043–55.

    Article  CAS  Google Scholar 

  29. Bao W, Bussel JB, Heck S, He W, Karpoff M, Boulad N, et al. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood. 2010;116:4639–45.

    Article  CAS  Google Scholar 

  30. Schifferli A, Kühne T. Thrombopoietin receptor agonists: a new immune modulatory strategy in immune thrombocytopenia? Semin Hematol. 2016;53:S31–4.

    Article  Google Scholar 

  31. Reid R, Bennett JM, Becker M, Chen Y, Milner L, Phillips GL 2nd, et al. Use of eltrombopag, a thrombopoietin receptor agonist, in post-transplantation thrombocytopenia. Am J Hematol. 2012;87:743–5.

    Article  CAS  Google Scholar 

  32. Tanaka T, Inamoto Y, Yamashita T, Fuji S, Okinaka K, Kurosawa S, et al. Eltrombopag for treatment of thrombocytopenia after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:919–24.

    Article  CAS  Google Scholar 

  33. Dyba J, Tinmouth A, Bredeson C, Matthews J, Allan DS. Eltrombopag after allogeneic haematopoietic cell transplantation in a case of poor graft function and systematic review of the literature. Transfus Med. 2016;26:202–7.

    Article  CAS  Google Scholar 

  34. Tang C, Chen F, Kong D, Ma Q, Dai H, Yin J, et al. Successful treatment of secondary poor graft function post allogeneic hematopoietic stem cell transplantation with eltrombopag. J Hematol Oncol. 2018;11:103.

    Article  Google Scholar 

  35. Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014;123:1818–25.

    Article  CAS  Google Scholar 

  36. Bento L, Bastida JM, García-Cadenas I, García-Torres E, Rivera D, Bosch-Vilaseca A, et al. Thrombopoietin receptor agonists for severe thrombocytopenia after allogeneic stem cell transplantation: experience of the Spanish Group of Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2019;25:1825–31.

    Article  CAS  Google Scholar 

  37. Yuan C, Boyd AM, Nelson J, Patel RD, Varela JC, Goldstein SC, et al. Eltrombopag for treating thrombocytopenia after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:1320–4.

    Article  CAS  Google Scholar 

  38. Ghanima W, Geyer JT, Lee CS, Boiocchi L, Imahiyerobo AA, Orazi A, et al. Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-receptor agonists: a single-center, long-term follow-up. Haematologica. 2014;99:937–44.

    Article  Google Scholar 

  39. Smieliauskas F, Chien CR, Shen C, Geynisman DM, Shih YC. Cost-effectiveness analyses of targeted oral anti-cancer drugs: a systematic review. PharmacoEconomics. 2014;32:651–80.

    Article  Google Scholar 

  40. Raut SS, Shah SA, Sharanangat VV, Shah KM, Patel KA, Anand AS, et al. Safety and efficacy of eltrombopag in post-hematopoietic stem cell transplantation (HSCT) thrombocytopenia. Indian J Hematol Blood Transfus. 2015;31:413–5.

    Article  Google Scholar 

Download references

Funding

There is no funding source to disclose for this study. Few of the patients received compassionate use of the drug Eltrombopag from NovartisTM.

Author information

Authors and Affiliations

  1. Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, Toronto, ON, Canada

    Ram Vasudevan Nampoothiri, Lina Ho, Cassandra McEwan, Ivan Pasic, Wilson Lam, Arjun Datt Law, Fotios V. Michelis, Santhosh Thyagu, Dennis (Dong Hwan) Kim, Armin Gerbitz, Auro Viswabandya, Jeffrey Howard Lipton, Jonas Mattsson & Rajat Kumar

Authors
  1. Ram Vasudevan Nampoothiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lina Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cassandra McEwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivan Pasic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wilson Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arjun Datt Law
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fotios V. Michelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Santhosh Thyagu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dennis (Dong Hwan) Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Armin Gerbitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Auro Viswabandya
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jeffrey Howard Lipton
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jonas Mattsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Rajat Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajat Kumar.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nampoothiri, R.V., Ho, L., McEwan, C. et al. Efficacy and cost analysis of eltrombopag in thrombocytopenia and poor graft function post allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 56, 2471–2476 (2021). https://doi.org/10.1038/s41409-021-01362-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-021-01362-2

This article is cited by

Search

Advanced search

Quick links