nach oben

Indian Journal of Hematology and Blood Transfusion

Erschienen in:

24.09.2019 | Review Article

Eltrombopag: Role in Cytopenias Following Hematopoietic Stem Cell Transplantation

verfasst von: Ram Vasudevan Nampoothiri, Rajat Kumar

Erschienen in: Indian Journal of Hematology and Blood Transfusion | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Eltrombopag is a small molecule oral agonist of the thrombopoietin receptor. Initially used for improving thrombocytopenia in chronic immune thrombocytopenia (ITP), it was later found to be efficacious in various other etiologies of thrombocytopenia as well as inherited marrow failure syndromes. Lately, it has been used for thrombocytopenia and poor graft function after allogeneic hematopoietic stem cell transplantation (HSCT) without any severe adverse events. Although prospective evidence of the efficacy is limited, there are increasing reports on the safety and efficacy with Eltrombopag in post HSCT thrombocytopenia and poor graft function. This provides an exciting opportunity for further research to evaluate both efficacy and cost-effectiveness of the use of Eltrombopag in this scenario. Here we review the current evidence on the indications for the use of Eltrombopag in the post allogeneic hematopoietic stem cell transplant setting.

Erhardt J, Erickson-Miller CL, Tapley P (2004) SB 497115-GR, a low molecular weight TPOR agonist, does not induce platelet activation or enhance agonist-induced platelet aggregation in vitro. Blood 104:3888CrossRef

Jenkins JM, Williams DF, Deng Y, Deng YF, Uhl J, Uhl JF, Kitchen V, Kitchen VF, Collins D, Collins DF, Erickson-Miller CL et al (2007) Phase 1 clinical study of Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 109(11):4739–4741CrossRef

Imbach P, Crowther M (2011) Thrombopoietin-receptor agonists for primary immune thrombocytopenia. N Engl J Med 365(8):734–741. https://doi.org/10.1056/NEJMct1014202 CrossRefPubMed

Kalota A, Brennan K, Erickson-Miller CL, Danet G, Carroll M, Gewirtz AM (2004) Effects of SB559457, a novel small molecule thrombopoietin receptor (TpoR) agonist, on human hematopoietic cell growth and differentiation. Blood 104:2913CrossRef

Provan D, Saleh M, Goodison S, Rafi R, Stone N, Hamilton JM, et al (2006) The safety profile of Eltrombopag, a novel oral platelet growth factor, in thrombocytopenic patients and healthy subjects. J Clin Oncol 24(18_suppl):18596CrossRef

Sellers T, Hart T, Semanik M, Murthy K (2004) Pharmacology and safety of SB-497115-GR, an orally active small molecular weight TPO receptor agonist, in chimpanzees, rats and dogs. Blood 104:2063CrossRef

Bussel JB, Cheng GF, Saleh MN, Saleh MF, Psaila B, Psaila BF, Kovaleva L, Kovaleva LF, Meddeb B, Meddeb BF, Kloczko J et al (2007) Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 357(22):2237–2247CrossRef

McHutchison JG, Dusheiko GF, Shiffman ML, Shiffman MF, Rodriguez-Torres M, Rodriguez-Torres MF, Sigal S, Sigal SF, Bourliere M, Bourliere MF, Berg T, et al. (2007) Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. New Engl J Med 357:2227–2236CrossRef

Eltrombopag FDA approval Letter for Chronic ITP Reference ID 4162520 FDA.pdf

10.

Olnes MJ, Scheinberg PF, Calvo KR, Calvo KF, Desmond R, Desmond RF, Tang Y, Tang YF, Dumitriu B, Dumitriu BF, Parikh AR et al (2012) Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 367(1):11–19. https://doi.org/10.1056/NEJMoa1200931 CrossRefPubMedPubMedCentral

11.

Yoshihara H, Arai FF, Hosokawa K, Hosokawa KF, Hagiwara T, Hagiwara TF, Takubo K, Takubo KF, Nakamura Y, Nakamura YF, Gomei Y et al (2007) Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 1(6):685–697. https://doi.org/10.1016/j.stem.2007.10.020 CrossRefPubMed

12.

Alexander WS, Roberts AF, Nicola NA, Nicola NF, Li R, Li RF, Metcalf D, Metcalf D (1996) Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood 87(6):2162–2170CrossRef

13.

Zeigler FC, de Sauvage FF, Widmer HR, Widmer HF, Keller GA, Keller GF, Donahue C, Donahue CF, Schreiber RD, Schreiber RF, Malloy B et al (1994) In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand (TPO) on purified murine hematopoietic stem cells. Blood 84(12):4045–4052CrossRef

14.

Ballmaier M, Germeshausen MF, Krukemeier S, Krukemeier SF, Welte K, Welte K (2003) Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia. Ann N Y Acad Sci 996:17–25CrossRef

15.

Tonelli R, Scardovi AF, Pession A, Pession AF, Strippoli P, Strippoli PF, Bonsi L, Bonsi LF, Vitale L, Vitale LF, Prete A et al (2000) Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT). Hum Genet 107(3):225–233CrossRef

16.

Bao W, Bussel JF, Heck S, Heck SF, He W, He WF, Karpoff M, Karpoff MF, Boulad N, Boulad NF, Yazdanbakhsh K et al (2010) Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood 116(22):4639–4645. https://doi.org/10.1182/blood-2010-04-281717 CrossRefPubMedPubMedCentral

17.

Schifferli A, Kuhne T (2016) Thrombopoietin receptor agonists: a new immune modulatory strategy in immune thrombocytopenia?. Semin Hematol 53(Suppl 1):S31–S34. https://doi.org/10.1053/j.seminhematol.2016.04.010 CrossRefPubMed

18.

Alvarado LJAO, Huntsman HD, Cheng H, Townsley DM, Winkler T, Feng X et al (2019) Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-γ. Blood 133(19):2043–2055. https://doi.org/10.1182/blood-2018-11-884486 CrossRefPubMedPubMedCentral

19.

Vlachodimitropoulou E, Chen YL, Garbowski M, Koonyosying P, Psaila B, Sola-Visner M et al (2017) Eltrombopag: a powerful chelator of cellular or extracellular iron(III) alone or combined with a second chelator. Blood 130(17):1923–1933. https://doi.org/10.1182/blood-2016-10-740241 CrossRefPubMedPubMedCentral

20.

Zhao Z, Sun Q, Sokoll LJ, Streiff M, Cheng Z, Grasmeder S et al (2018) Eltrombopag mobilizes iron in patients with aplastic anemia. Blood 131:2399–2402CrossRef

21.

Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O et al (2017) Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med 376(16):1540–1550. https://doi.org/10.1056/NEJMoa1613878 CrossRefPubMedPubMedCentral

22.

https://www.novartis.com/news/media-releases/fda-approves-novartis-drug-promacta-first-line-saa-and-grants-breakthrough-therapy-designation-additional-new-indication

23.

Desmond R, Townsley DF, Dumitriu B, Dumitriu BF, Olnes MJ, Olnes MF, Scheinberg P, Scheinberg PF, Bevans M, Bevans MF, Parikh AR et al (2014) Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood 123(12):1818–1825. https://doi.org/10.1182/blood-2013-10-534743 CrossRefPubMedPubMedCentral

24.

Winkler T, Fan X, Cooper J, Desmond R, Young DJ, Townsley DM et al (2019) Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood 133(24):2575–2585. https://doi.org/10.1182/blood.2019000478 CrossRefPubMed

25.

Akahoshi Y, Kanda J, Gomyo A, Hayakawa J, Komiya Y, Harada N et al (2016) Risk factors and impact of secondary failure of platelet recovery after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 22(9):1678–1683. https://doi.org/10.1016/j.bbmt.2016.06.003 CrossRefPubMed

26.

Nash RA, Gooley TF, Davis C, Davis CF, Appelbaum FR, Appelbaum FR (1996) The problem of thrombocytopenia after hematopoietic stem cell transplantation. Stem Cells 14(Suppl 1):261–273CrossRef

27.

Bruno B, Gooley TF, Sullivan KM, Sullivan KF, Davis C, Davis CF, Bensinger WI, Bensinger WF, Storb R, Storb RF, Nash RA et al (2001) Secondary failure of platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 7(3):154–162CrossRef

28.

First LF, Smith BR, Smith BF, Lipton J, Lipton JF, Nathan DG, Nathan DF, Parkman R, Parkman RF, Rappeport JM, Rappeport JM (1985) Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes. Blood 65(2):368–374CrossRef

29.

Yamazaki R, Kuwana MF, Mori T, Mori TF, Okazaki Y, Okazaki YF, Kawakami Y, Kawakami YF, Ikeda Y, Ikeda YF, Okamoto S et al (2006) Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover. Bone Marrow Transplant 38(5):377–384CrossRef

30.

Zhang X, Fu HF, Xu L, Xu LF, Liu D, Liu DF, Wang J, Wang JF, Liu K, Liu KF, Huang X et al (2011) 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 17(2):274–280. https://doi.org/10.1016/j.bbmt.2010.09.007 CrossRefPubMed

31.

Marsh JC, Mufti GJ (2014) Eltrombopag: a stem cell cookie? Blood 123(12):1774–1775. https://doi.org/10.1182/blood-2014-02-553404 CrossRefPubMed

32.

Reid R, Bennett JF, Becker M, Becker MF, Chen Y, Chen YF, Milner L, Milner LF, Phillips GL 2nd, Phillips GL 2nd, Liesveld J et al (2012) Use of Eltrombopag, a thrombopoietin receptor agonist, in post-transplantation thrombocytopenia. Am J Hematol 87(7):743–745. https://doi.org/10.1002/ajh.23225 CrossRefPubMed

33.

Liesveld JL, Phillips GL 2nd, Becker M, Becker MF, Constine LS, Constine LF, Friedberg J, Friedberg JF, Andolina JR, Andolina F Jr, Milner LA et al (2013) A phase 1 trial of Eltrombopag in patients undergoing stem cell transplantation after total body irradiation. Biol Blood Marrow Transplant 19(12):1745–1752. https://doi.org/10.1016/j.bbmt.2013.10.002 CrossRefPubMed

34.

Raut SS, Shah SA, Sharanangat VV, Shah KM, Patel KA, Anand AS et al (2015) Safety and efficacy of Eltrombopag in post-hematopoietic stem cell transplantation (HSCT) thrombocytopenia. Indian J Hematol Blood Transfus 31(4):413–415. https://doi.org/10.1007/s12288-014-0491-0 CrossRefPubMed

35.

Tanaka T, Inamoto Y, Yamashita T, Fuji S, Okinaka K, Kurosawa S et al (2016) Eltrombopag for treatment of thrombocytopenia after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 22(5):919–924. https://doi.org/10.1016/j.bbmt.2016.01.018 CrossRefPubMed

36.

Popat UR, Ray G, Bassett RL, Poon M-YC, Valdez BC, Konoplev S et al (2015) Eltrombopag for post-transplant thrombocytopenia: results of phase II randomized double blind placebo controlled trial. Blood 126(23):738CrossRef

37.

Bento L, Bastida JM, García-Cadenas I, García-Torres E, Rivera D, Bosch A et al (2018) Thrombopoietin receptor agonists for severe thrombocytopenia after allogeneic stem cell transplantation: experience of a multicenter study from the Grupo Español De Trasplante Hematopoyético (GETH). Blood 132(Suppl 1):200CrossRef

38.

Yuan C, Boyd AM, Nelson J, Patel RD, Varela JC, Goldstein SC et al (2019) Eltrombopag for treating thrombocytopenia after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. https://doi.org/10.1016/j.bbmt.2019.01.027 CrossRefPubMed

39.

Olsson R, Remberger MF, Schaffer M, Schaffer MF, Berggren DM, Berggren DF, Svahn BM, Svahn BF, Mattsson J, Mattsson JF, Ringden O et al (2013) Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transplant 48(4):537–543. https://doi.org/10.1038/bmt.2012.239 CrossRefPubMed

40.

Lee KH, Lee JF, Choi SJ, Choi SF, Lee JH, Lee JF, Kim S, Kim SF, Seol M, Seol MF, Lee YS et al (2004) Failure of trilineage blood cell reconstitution after initial neutrophil engraftment in patients undergoing allogeneic hematopoietic cell transplantation–frequency and outcomes. Bone Marrow Transplant 33(7):729–734CrossRef

41.

Marotta S, Marano L, Ricci P, Cacace F, Frieri C, Simeone L et al (2019) Eltrombopag for post-transplant cytopenias due to poor graft function. Bone Marrow Transplant. https://doi.org/10.1038/s41409-019-0442-3 CrossRefPubMed

42.

Davies SM, Kollman CF, Anasetti C, Anasetti CF, Antin JH, Antin JF, Gajewski J, Gajewski JF, Casper JT, Casper JF, Nademanee A et al (2000) Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood 96(13):4096–4102CrossRef

43.

Dominietto A, Raiola AF, van Lint MT, van Lint MF, Lamparelli T, Lamparelli TF, Gualandi F, Gualandi FF, Berisso G, Berisso GF, Bregante S et al (2001) Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft‐versus‐host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol 112(1):219–227CrossRef

44.

Stasia A, Ghiso A, Galaverna F, Raiola AM, Gualandi F, Luchetti S et al (2014) CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 20(9):1440–1443. https://doi.org/10.1016/j.bbmt.2014.05.016 CrossRefPubMed

45.

Dyba J, Tinmouth A, Bredeson C, Matthews J, Allan DS (2016) Eltrombopag after allogeneic haematopoietic cell transplantation in a case of poor graft function and systematic review of the literature. Transfus Med 26(3):202–207. https://doi.org/10.1111/tme.12300 CrossRefPubMed

46.

Master S, Dwary A, Mansour R, Mills GM, Koshy N (2018) Use of Eltrombopag in improving poor graft function after allogeneic hematopoietic stem cell transplantation. Case Rep Oncol 11(1):191–195. https://doi.org/10.1159/000487229 CrossRefPubMedPubMedCentral

47.

Tang C, Chen F, Kong D, Ma Q, Dai H, Yin J et al (2018) Successful treatment of secondary poor graft function post allogeneic hematopoietic stem cell transplantation with eltrombopag. J Hematol Oncol 11(1):103. https://doi.org/10.1186/s13045-018-0649-6 CrossRefPubMedPubMedCentral

48.

Fu H, Zhang X, Han T, Mo X, Wang Y, Chen H et al (2019) Eltrombopag is an effective and safe therapy for refractory thrombocytopenia after haploidentical hematopoietic stem cell transplantation. Bone Marrow Transplant. https://doi.org/10.1038/s41409-019-0435-2 CrossRefPubMed

49.

Will B, Kawahara M, Luciano JP, Bruns I, Parekh S, Erickson-Miller CL et al (2009) Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood 114(18):3899CrossRef

50.

Mittelman M, Platzbecker U, Afanasyev B, Grosicki S, Wong RSM, Anagnostopoulos A et al (2018) Eltrombopag for advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia (ASPIRE): a randomised, placebo-controlled, phase 2 trial. Lancet Haematol 5(1):e34–e43. https://doi.org/10.1016/S2352-3026(17)-4 CrossRefPubMed

51.

Mori S, Patel RD, Boyd A, Simon S, Nelson J, Goldstein SC (2018) Eltrombopag treatment for primary and secondary thrombocytopenia post allogeneic and autologous stem cell transplantation is effective and safe. Biol Blood Marrow Transplant 24(3):S343–S344CrossRef

52.

Wang TP, Alencar MC, Ramirez J, Oliva MV, Cisneros S, Jean P et al (2019) Clinical characteristics and response rates to Eltrombopag for primary and secondary thrombocytopenia after allogeneic hematopoietic stem cell transplant (HCT). Biol Blood Marrow Transplant 25(3):S135–S136CrossRef

53.

Vera Milovic AR, Nonaka C, Martinez G, Drelichman G, Feldman L, Real J (2018) Treatment of poor graft function after allogeneic SCT with Eltrombopag. Bone marrow transplantation with a booster of CD34-selected cells infused without conditioning. In: The 44th annual meeting of the european society for blood and marrow transplantation: physicians poster sessions, p 309

54.

Giammarco S, Sica S, Chiusolo P, Laurenti L, Sorá F, Martino M et al (2019) Eltrombopag for the treatment of late cytopenia following allogeneic stem cell transplants. Bone Marrow Transplant 54:144–619CrossRef

Titel: Eltrombopag: Role in Cytopenias Following Hematopoietic Stem Cell Transplantation
verfasst von: Ram Vasudevan Nampoothiri
Rajat Kumar
Publikationsdatum: 24.09.2019
Verlag: Springer India
Erschienen in: Indian Journal of Hematology and Blood Transfusion / Ausgabe 2/2020
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI: https://doi.org/10.1007/s12288-019-01194-7

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Eltrombopag: Role in Cytopenias Following Hematopoietic Stem Cell Transplantation

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2020

Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype

Combined Immature Platelet Fraction and Schistocyte Count to Differentiate Pregnancy-Associated Thrombotic Thrombocytopenic Purpura from Severe Preeclampsia/Haemolysis, Elevated Liver Enzymes, and Low Platelet Syndrome (SPE/HELLP)

Flow Cytometry Based MRD and Its Impact on Survival Outcome in Children and Young Adults with ALL: A Prospective Study from a Tertiary Cancer Centre in Southern India

Activity Wise Unit Cost of Blood Components in a Tertiary Care Hospital Blood Bank for the Year 2018

Molecular Characterization of G6PD Deficiency: Report of Three Novel G6PD Variants

Cannibalistic Hemophagocytosis in Acute Myeloid Leukemia with Trisomy 9

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie