Eltrombopag & Cyclosporine in Children With Sever Aplastic Anemia

Summary

Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.but,It is very serious disease causing morbidity and mortality. Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion. Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site of thrombopoietin therefore it does not compete for binding with the native molecule. It promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote other hematopoietic stem cell as well as in thrombopoiesis .

Timeline

Start

2017-12-20

Primary completion

2019-12-29

Completion

2020-01-05

Publications

• Background Guinan EC. Acquired aplastic anemia in childhood. Hematol Oncol Clin North Am. 2009 Apr;23(2):171-91. doi: 10.1016/j.hoc.2009.01.011.
• Background Young NS, Bacigalupo A, Marsh JC. Aplastic anemia: pathophysiology and treatment. Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S119-25. doi: 10.1016/j.bbmt.2009.09.013. Epub 2009 Sep 24.
• Background Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, Young NS. The epidemiology of aplastic anemia in Thailand. Blood. 2006 Feb 15;107(4):1299-307. doi: 10.1182/blood-2005-01-0161. Epub 2005 Oct 27.
• Background Marsh JC, Mufti GJ. Eltrombopag: a stem cell cookie? Blood. 2014 Mar 20;123(12):1774-5. doi: 10.1182/blood-2014-02-553404. No abstract available.
• Background Garnock-Jones KP, Keam SJ. Eltrombopag. Drugs. 2009;69(5):567-76. doi: 10.2165/00003495-200969050-00005.
• Background Montane E, Ibanez L, Vidal X, Ballarin E, Puig R, Garcia N, Laporte JR; Catalan Group for Study of Agranulocytosis and Aplastic Anemia. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica. 2008 Apr;93(4):518-23. doi: 10.3324/haematol.12020. Epub 2008 Mar 5.
• Background Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Mansson R, Thoren LA, Ekblom M, Alexander WS, Jacobsen SE. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. 2007 Dec 13;1(6):671-84. doi: 10.1016/j.stem.2007.10.008. Epub 2007 Nov 20.
• Background Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis. Blood. 2008 Feb 1;111(3):981-6. doi: 10.1182/blood-2007-05-088500.
• Background Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. doi: 10.1056/NEJMoa073275.
• Background de Laval B, Pawlikowska P, Petit-Cocault L, Bilhou-Nabera C, Aubin-Houzelstein G, Souyri M, Pouzoulet F, Gaudry M, Porteu F. Thrombopoietin-increased DNA-PK-dependent DNA repair limits hematopoietic stem and progenitor cell mutagenesis in response to DNA damage. Cell Stem Cell. 2013 Jan 3;12(1):37-48. doi: 10.1016/j.stem.2012.10.012. Epub 2012 Dec 13.
• Background Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012 Jul 5;367(1):11-9. doi: 10.1056/NEJMoa1200931.
• Background Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014 Mar 20;123(12):1818-25. doi: 10.1182/blood-2013-10-534743. Epub 2013 Dec 17.
• Background Alter BP. Aplastic Anemia, Pediatric Aspects. Oncologist. 1996;1(6):361-366.
• Background Ballmaier M, Germeshausen M, Krukemeier S, Welte K. 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. 2003 May;996:17-25. doi: 10.1111/j.1749-6632.2003.tb03228.x.
• Background Dezern AE, Brodsky RA. Clinical management of aplastic anemia. Expert Rev Hematol. 2011 Apr;4(2):221-30. doi: 10.1586/ehm.11.11.
• Background Gupta V, Eapen M, Brazauskas R, Carreras J, Aljurf M, Gale RP, Hale GA, Ilhan O, Passweg JR, Ringden O, Sabloff M, Schrezenmeier H, Socie G, Marsh JC. Impact of age on outcomes after bone marrow transplantation for acquired aplastic anemia using HLA-matched sibling donors. Haematologica. 2010 Dec;95(12):2119-25. doi: 10.3324/haematol.2010.026682. Epub 2010 Sep 17.
• Background Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, Killick SB, Stewart R, Yin JA; British Committee for Standards in Haematology. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009 Oct;147(1):43-70. doi: 10.1111/j.1365-2141.2009.07842.x. Epub 2009 Aug 10. No abstract available.
• Background Rauff B, Idrees M, Shah SA, Butt S, Butt AM, Ali L, Hussain A, Irshad-Ur-Rehman, Ali M. Hepatitis associated aplastic anemia: a review. Virol J. 2011 Feb 28;8:87. doi: 10.1186/1743-422X-8-87.
• Background Young NS. Pathophysiologic mechanisms in acquired aplastic anemia. Hematology Am Soc Hematol Educ Program. 2006:72-7. doi: 10.1182/asheducation-2006.1.72.
• Background Zhang J, Yang T. [Meta-analysis of association between organophosphorus pesticides and aplastic anemia]. Zhonghua Liu Xing Bing Xue Za Zhi. 2015 Sep;36(9):1005-9. Chinese.
• Background Wu Y, Yu J, Zhang L, Luo Q, Xiao JW, Liu XM, Xian Y, Dai BT, Xu YH, Su YC. [Hematopoiesis support of mesenchymal stem cells in children with aplastic anemia]. Zhongguo Dang Dai Er Ke Za Zhi. 2008 Aug;10(4):455-9. Chinese.
• Background Scheinberg P. Aplastic anemia: therapeutic updates in immunosuppression and transplantation. Hematology Am Soc Hematol Educ Program. 2012;2012:292-300. doi: 10.1182/asheducation-2012.1.292.
• Background Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011 Aug 4;365(5):430-8. doi: 10.1056/NEJMoa1103975.
• Background Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017 Apr 20;376(16):1540-1550. doi: 10.1056/NEJMoa1613878.

Drugs

Indications

No indication recorded.