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Gill H, Wong RSM, Kwong YL. From chronic immune thrombocytopenia to severe aplastic anemia: recent insights into the evolution of eltrombopag. Ther Adv Hematol. 2017;8(5):159-174doi: 10.1177/2040620717693573.
Gill, H., Wong, R. S. M., & Kwong, Y. L. (2017). From chronic immune thrombocytopenia to severe aplastic anemia: recent insights into the evolution of eltrombopag. Therapeutic advances in hematology, 8(5), 159-174. https://doi.org/10.1177/2040620717693573
Gill, Harinder, et al. "From chronic immune thrombocytopenia to severe aplastic anemia: recent insights into the evolution of eltrombopag." Therapeutic advances in hematology vol. 8,5 (2017): 159-174. doi: https://doi.org/10.1177/2040620717693573
Gill H, Wong RSM, Kwong YL. From chronic immune thrombocytopenia to severe aplastic anemia: recent insights into the evolution of eltrombopag. Ther Adv Hematol. 2017 May;8(5):159-174. doi: 10.1177/2040620717693573. Epub 2017 Feb 01. PMID: 28473904; PMCID: PMC5407506.
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Ther Adv Hematol. 2017 May;8(5):159-174. doi: 10.1177/2040620717693573. Epub 2017 Feb 01.

From chronic immune thrombocytopenia to severe aplastic anemia: recent insights into the evolution of eltrombopag.

Therapeutic advances in hematology

Harinder Gill, Raymond S M Wong, Yok-Lam Kwong

Affiliations

  1. Department of Medicine, Queen Mary Hospital, Hong Kong, China.
  2. Sir Y.K. Pao Centre for Cancer and Department of Medicine and Therapeutics, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, China.
  3. Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.

PMID: 28473904 PMCID: PMC5407506 DOI: 10.1177/2040620717693573

Abstract

Thrombopoietin (TPO) is the most potent cytokine stimulating thrombopoiesis. Therapy with exogenous TPO is limited by the formation of antibodies cross-reacting with endogenous TPO. Mimetics of TPO are compounds with no antigenic similarity to TPO. Eltrombopag is an orally-active nonpeptide small molecule that binds to the transmembrane portion of the TPO receptor MPL. Initial trials of eltrombopag have centered on immune thrombocytopenia (ITP), which is due to both increased destruction and decreased production of platelets. Eltrombopag at 25-75 mg/day has been shown to be highly effective in raising the platelet count in ITP with suboptimal response to immunosuppression and splenectomy. These successful results led to the exploration of eltrombopag in other thrombocytopenic disorders. In hepatitis C viral infection, eltrombopag raises the platelet count sufficiently enough to allow treatment with ribavirin and pegylated interferon. Because MPL is expressed on hematopoietic cells, eltrombopag use in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) might enhance leukemic proliferation. Clinical trials of eltrombopag in MDS and AML, however, have shown amelioration of thrombocytopenia without promoting disease progression. In severe aplastic anemia (SAA) not responding to immunosuppression with anti-thymocyte globulin (ATG) and cyclosporine, eltrombopag as a single agent at 150-300 mg/day results in an overall response rate of 40-70%. At high doses, adverse effects including pigmentation, gastrointestinal upset and hepatic derangement have become evident. Current studies have examined the first-line use of eltrombopag in combination with ATG in SAA. In a recent study, eltrombopag used at 150 mg/day with horse ATG resulted in an overall response rate of 90% in newly diagnosed SAA patients, with a complete response rate of about 50%. Clonal karyotypic aberrations are, however, found in 10-20% of SAA patients treated with eltrombopag. The safety and efficacy of eltrombopag in SAA require further evaluation, particularly when it is used with less intensive immunosuppression.

Keywords: acute myeloid leukemia; eltrombopag; hematopoietic stem cell transplantation; hepatitis C virus; immune thrombocytopenia; myelodysplastic syndrome; severe aplastic anemia

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

References

  1. Blood. 1996 Jun 15;87(12):4998-5005 - PubMed
  2. BMC Cancer. 2013 Mar 16;13:121 - PubMed
  3. J Biol Chem. 1995 Mar 10;270(10 ):4979-82 - PubMed
  4. Lancet. 2006 Nov 25;368(9550):1894-907 - PubMed
  5. Semin Hematol. 2016 Apr;53 Suppl 1:S31-4 - PubMed
  6. J Biol Chem. 2001 Jan 26;276(4):2494-502 - PubMed
  7. Blood. 2002 Nov 15;100(10):3457-69 - PubMed
  8. Semin Hematol. 2015 Jan;52(1):4-11 - PubMed
  9. Br J Haematol. 2016 Jan;172(2):187-207 - PubMed
  10. Blood. 2004 Feb 15;103(4):1364-9 - PubMed
  11. Alcohol Clin Exp Res. 1989 Oct;13(5):706-20 - PubMed
  12. J Hepatol. 1996 Feb;24(2):135-40 - PubMed
  13. Blood. 1998 May 15;91(10):3637-45 - PubMed
  14. Core Evid. 2006;1(4):221-31 - PubMed
  15. Blood Rev. 2002 Mar;16(1):57-9 - PubMed
  16. Am J Hematol. 2016 May;91(5):E293-5 - PubMed
  17. Hepatology. 2015 May;61(5):1512-22 - PubMed
  18. Cancer. 2007 May 1;109(9):1705-14 - PubMed
  19. Aliment Pharmacol Ther. 2006 Apr 15;23(8):1055-65 - PubMed
  20. Hepatology. 2003 Jun;37(6):1267-76 - PubMed
  21. Leukemia. 2016 Mar;30(3):536-44 - PubMed
  22. Blood. 2012 Jul 12;120(2):386-94 - PubMed
  23. Int J Oncol. 2015 Nov;47(5):1696-702 - PubMed
  24. Blood. 2001 Dec 1;98(12):3241-8 - PubMed
  25. Nature. 1994 Jun 16;369(6481):533-8 - PubMed
  26. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11104-8 - PubMed
  27. Cell. 1994 Jul 1;77(7):1117-24 - PubMed
  28. Leukemia. 2013 Apr;27(5):1207-10 - PubMed
  29. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):13023-7 - PubMed
  30. N Engl J Med. 2007 Nov 29;357(22):2237-47 - PubMed
  31. J Clin Pharmacol. 2011 Jun;51(6):842-56 - PubMed
  32. Blood. 1994 Dec 15;84(12):4045-52 - PubMed
  33. Blood. 1993 Aug 1;82(3):877-83 - PubMed
  34. Blood. 1997 Sep 15;90(6):2234-43 - PubMed
  35. FEBS Lett. 1995 Aug 14;370(1-2):63-8 - PubMed
  36. Lancet. 2013 Jun 15;381(9883):2100-7 - PubMed
  37. Br J Haematol. 2014 Apr;165(2):259-68 - PubMed
  38. Gastroenterology. 2002 Jul;123(1):141-51 - PubMed
  39. Platelets. 2015 ;26(1):83-6 - PubMed
  40. Blood. 2014 Mar 20;123(12 ):1818-25 - PubMed
  41. Blood. 1994 Aug 1;84(3):941-9 - PubMed
  42. Drug Saf. 2011 Dec 1;34(12):1151-60 - PubMed
  43. N Engl J Med. 2015 Jul 2;373(1):35-47 - PubMed
  44. Blood. 2011 Apr 21;117(16):4190-207 - PubMed
  45. Cancer. 2008 Sep 15;113(6):1351-61 - PubMed
  46. Blood. 1996 Jun 1;87(11):4544-51 - PubMed
  47. Gut. 2005 Jul;54(7):1014-20 - PubMed
  48. J Clin Pharmacol. 2011 Oct;51(10 ):1403-17 - PubMed
  49. Ther Adv Hematol. 2012 Jun;3(3):155-64 - PubMed
  50. Br J Haematol. 2014 Apr;165(2):248-58 - PubMed
  51. BMC Cancer. 2012 Sep 11;12 :405 - PubMed
  52. Lancet. 2009 Feb 21;373(9664):641-8 - PubMed
  53. Thromb Haemost. 1998 Jun;79(6):1101-5 - PubMed
  54. Nature. 1994 Jun 16;369(6481):565-8 - PubMed
  55. Exp Hematol. 2000 Oct;28(10):1158-63 - PubMed
  56. Blood. 2009 Oct 29;114(18):3899-908 - PubMed
  57. Oncology (Williston Park). 2015 Apr;29(4):295-6 - PubMed
  58. Can J Gastroenterol. 2000 Nov;14 Suppl D:60D-66D - PubMed
  59. N Engl J Med. 2014 May 22;370(21):1973-82 - PubMed
  60. Am J Hematol. 2015 Jul;90(7):598-601 - PubMed
  61. Blood. 2002 Apr 1;99(7):2599-602 - PubMed
  62. J Thromb Haemost. 2014 Aug;12(8):1266-73 - PubMed
  63. Biochem Biophys Res Commun. 1995 Dec 5;217(1):230-7 - PubMed
  64. Eur J Haematol. 2014 Nov;93(5):439-45 - PubMed
  65. Lancet Haematol. 2015 Aug;2(8):e315-25 - PubMed
  66. Int J Hematol. 2013 Jul;98(1):10-23 - PubMed
  67. Lancet Haematol. 2015 Oct;2(10):e417-26 - PubMed
  68. Scand J Clin Lab Invest. 2015 Jan;75(1):13-7 - PubMed
  69. J Cell Physiol. 1997 Apr;171(1):28-33 - PubMed
  70. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2350-5 - PubMed
  71. Biol Blood Marrow Transplant. 2016 May;22(5):919-24 - PubMed
  72. J Biochem. 1995 Jul;118(1):229-36 - PubMed
  73. Cancer Med. 2015 Jan;4(1):16-26 - PubMed
  74. Lancet. 2011 Jan 29;377(9763):393-402 - PubMed
  75. Curr Med Res Opin. 2010 Oct;26(10 ):2339-46 - PubMed
  76. Gastroenterology. 2014 Feb;146(2):442-52.e1 - PubMed
  77. Haematologica. 2010 Jul;95(7):1167-75 - PubMed
  78. N Engl J Med. 2012 Jul 5;367 (1):11-9 - PubMed
  79. Am J Clin Pathol. 2002 Jun;117(6):844-50 - PubMed
  80. N Engl J Med. 2012 Aug 23;367 (8):716-24 - PubMed
  81. Br J Haematol. 1996 Jun;93(3):704-6 - PubMed
  82. Br J Haematol. 2017 Mar;176(6):991-994 - PubMed
  83. Curr Opin Hematol. 1998 May;5(3):203-8 - PubMed
  84. Blood. 2013 Nov 21;122(22):3561-7 - PubMed
  85. FEBS Lett. 1995 Dec 27;377(3):497-501 - PubMed
  86. Leuk Res. 2010 Sep;34(9):1224-31 - PubMed
  87. Br J Haematol. 1998 Mar;100(3):571-6 - PubMed
  88. PLoS One. 2015 Apr 27;10(4):e0126691 - PubMed
  89. Biol Blood Marrow Transplant. 2013 Dec;19(12 ):1745-52 - PubMed
  90. Semin Hematol. 2010 Jul;47(3):249-57 - PubMed
  91. N Engl J Med. 2007 Nov 29;357(22):2227-36 - PubMed
  92. Semin Hematol. 2015 Jan;52(1):31-7 - PubMed
  93. Thromb Haemost. 1995 Jul;74(1):521-5 - PubMed
  94. Stem Cells. 2000;18(2):112-9 - PubMed
  95. Lancet. 2015 Oct 24;386(10004):1649-58 - PubMed
  96. Leuk Res. 2000 May;24(5):401-9 - PubMed

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