Effective Treatment of Refractory Acquired Pure Red Blood Cell Aplasia with Eltrombopag and Sirolimus: a Case Report

Overview

Journal Ther Adv Hematol

Specialty Hematology

Date 2020 Aug 1

PMID 32733663

Authors

Yuzhou Huang

Xianyong Jiang

Bing Han

Affiliations

Soon will be listed here.

Abstract

Acquired pure red cell aplasia (aPRCA) is a kind of anemia characterized by severe reticulocytopenia and reduced bone marrow erythroblastic cells. For patients who are refractory to the first-line therapy (cyclosporin A with/without glucocorticoids), second-line therapy is considered less effective. We report on a patient with primary aPRCA who was refractory to cyclosporin A, glucocorticoids, and several second-line regimens. The patient was treated with sirolimus for 10 months with no improvement in hemoglobin but complete response was achieved after adding eltrombopag at a dosage of 25 mg/day. Eltrombopag was well tolerated with no evidence of clonal evolution at the end of follow up. This case provided a new attempt at treating patients with refractory/relapse aPRCA with eltrombopag, probably in combination with sirolimus.

References

Alvarado L, Huntsman H, Cheng H, Townsley D, Winkler T, Feng X . Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-γ. Blood. 2019; 133(19):2043-2055. PMC: 6509545. DOI: 10.1182/blood-2018-11-884486. View

Lengline E, Drenou B, Peterlin P, Tournilhac O, Abraham J, Berceanu A . Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia. Haematologica. 2017; 103(2):212-220. PMC: 5792265. DOI: 10.3324/haematol.2017.176339. View

Sun H, Tsai Y, Nowak I, Liesveld J, Chen Y . Eltrombopag, a thrombopoietin receptor agonist, enhances human umbilical cord blood hematopoietic stem/primitive progenitor cell expansion and promotes multi-lineage hematopoiesis. Stem Cell Res. 2012; 9(2):77-86. PMC: 3412938. DOI: 10.1016/j.scr.2012.05.001. View

Means Jr R . Pure red cell aplasia. Blood. 2016; 128(21):2504-2509. DOI: 10.1182/blood-2016-05-717140. View

Sawada K, Fujishima N, Hirokawa M . Acquired pure red cell aplasia: updated review of treatment. Br J Haematol. 2008; 142(4):505-14. PMC: 2592349. DOI: 10.1111/j.1365-2141.2008.07216.x. View

Sawada K, Hirokawa M, Fujishima N . Diagnosis and management of acquired pure red cell aplasia. Hematol Oncol Clin North Am. 2009; 23(2):249-59. DOI: 10.1016/j.hoc.2009.01.009. View

Kim T, Despotovic J, Lambert M . Eltrombopag for use in children with immune thrombocytopenia. Blood Adv. 2018; 2(4):454-461. PMC: 5858473. DOI: 10.1182/bloodadvances.2017010660. View

Fattizzo B, Levati G, Cassin R, Barcellini W . Eltrombopag in Immune Thrombocytopenia, Aplastic Anemia, and Myelodysplastic Syndrome: From Megakaryopoiesis to Immunomodulation. Drugs. 2019; 79(12):1305-1319. DOI: 10.1007/s40265-019-01159-0. View

Scheinberg P . Activity of eltrombopag in severe aplastic anemia. Hematology Am Soc Hematol Educ Program. 2018; 2018(1):450-456. PMC: 6245975. DOI: 10.1182/asheducation-2018.1.450. View

10.

Teachey D, Lambert M . Diagnosis and management of autoimmune cytopenias in childhood. Pediatr Clin North Am. 2013; 60(6):1489-511. PMC: 5384653. DOI: 10.1016/j.pcl.2013.08.009. View

11.

Oliva E, Ronco F, Marino A, Alati C, Pratico G, Nobile F . Iron chelation therapy associated with improvement of hematopoiesis in transfusion-dependent patients. Transfusion. 2010; 50(7):1568-70. DOI: 10.1111/j.1537-2995.2010.02617.x. View

12.

Cazzola M, Della Porta M, Malcovati L . Clinical relevance of anemia and transfusion iron overload in myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program. 2008; :166-75. DOI: 10.1182/asheducation-2008.1.166. View

13.

Yoshida S, Konishi T, Nishizawa T, Yoshida Y . Effect of tacrolimus in a patient with pure red-cell aplasia. Clin Lab Haematol. 2005; 27(1):67-9. DOI: 10.1111/j.1365-2257.2004.00654.x. View

14.

Auner H, Wolfler A, Beham-Schmid C, Strunk D, Linkesch W, Sill H . Restoration of erythropoiesis by rituximab in an adult patient with primary acquired pure red cell aplasia refractory to conventional treatment. Br J Haematol. 2002; 116(3):727-8. DOI: 10.1046/j.1365-2141.2002.3317_3.x. View

15.

Chaoul N, Fayolle C, Desrues B, Oberkampf M, Tang A, Ladant D . Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication. Cancer Res. 2015; 75(16):3279-91. DOI: 10.1158/0008-5472.CAN-15-0454. View

16.

Shahan J, Hildebrandt G . Successful treatment of refractory pure red cell aplasia with bortezomib after allogeneic haematopoietic cell transplantation in a patient with alpha-beta subcutaneous panniculitis-like T cell lymphoma. Transfus Med. 2015; 25(5):342-4. DOI: 10.1111/tme.12216. View

17.

Lum S, Grainger J . Eltrombopag for the treatment of aplastic anemia: current perspectives. Drug Des Devel Ther. 2016; 10:2833-2843. PMC: 5028092. DOI: 10.2147/DDDT.S95715. View

18.

Hirokawa M, Sawada K, Fujishima N, Teramura M, Bessho M, Dan K . Long-term outcome of patients with acquired chronic pure red cell aplasia (PRCA) following immunosuppressive therapy: a final report of the nationwide cohort study in 2004/2006 by the Japan PRCA collaborative study group. Br J Haematol. 2015; 169(6):879-86. DOI: 10.1111/bjh.13376. View

19.

Desmond R, Townsley D, Dumitriu B, Olnes M, Scheinberg P, Bevans M . Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2013; 123(12):1818-25. PMC: 3962161. DOI: 10.1182/blood-2013-10-534743. View

20.

Long Z, Yu F, Du Y, Li H, Chen M, Zhuang J . Successful treatment of refractory/relapsed acquired pure red cell aplasia with sirolimus. Ann Hematol. 2018; 97(11):2047-2054. DOI: 10.1007/s00277-018-3431-5. View