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What Pediatricians Need to Know About Acquired Aplastic Anemia

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Benign Hematologic Disorders in Children

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Abstract

Acquired aplastic anemia (AA) is a rare and life-threatening immune-mediated hematopoietic disorder. Advances in supportive care have greatly improved outcomes, while immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT) have been the mainstay of treatment. However, newer therapies added to IST have shown improved response. The aim for this chapter is to provide pediatricians with better understanding of AA, its differential diagnoses, and to emphasize the importance of rapid and accurate recognition and management of AA.

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References

  1. Kaufman DW. The drug etiology of agranulocytosis and aplastic anemia. New York: Oxford University Press; 1991.

    Google Scholar 

  2. Cartwright RA, McKinney PA, Williams L, Miller JG, Evans DI, Bentley DP, et al. Aplastic anaemia incidence in parts of the United Kingdom in 1985. Leuk Res. 1988;12(6):459–63.

    Article  CAS  PubMed  Google Scholar 

  3. Mary JY, Baumelou E, Guiguet M. Epidemiology of aplastic anemia in France: a prospective multicentric study. The French Cooperative Group for epidemiological study of aplastic anemia. Blood. 1990;75(8):1646–53.

    Article  CAS  PubMed  Google Scholar 

  4. Montane E, Ibanez L, Vidal X, Ballarin E, Puig R, Garcia N, et al. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica. 2008;93(4):518–23.

    Article  PubMed  Google Scholar 

  5. Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, et al. The epidemiology of aplastic anemia in Thailand. Blood. 2006;107(4):1299–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jeong DC, Chung NG, Kang HJ, Koo HH, Kook H, Kim SK, et al. Epidemiology and clinical long-term outcome of childhood aplastic anemia in Korea for 15 years: retrospective study of the Korean Society of Pediatric Hematology Oncology (KSPHO). J Pediatr Hematol Oncol. 2011;33(3):172–8.

    Article  PubMed  Google Scholar 

  7. Wilson DB, Link DC, Mason PJ, Bessler M. Inherited bone marrow failure syndromes in adolescents and young adults. Ann Med. 2014;46(6):353–63.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fogarty PF, Yamaguchi H, Wiestner A, Baerlocher GM, Sloand E, Zeng WS, et al. Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA. Lancet. 2003;362(9396):1628–30.

    Article  CAS  PubMed  Google Scholar 

  9. Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Thamprasit T, Sirijirachai J, et al. Low drug attributability of aplastic anemia in Thailand. The Aplastic Anemia Study Group. Blood. 1997;89(11):4034–9.

    CAS  PubMed  Google Scholar 

  10. young NS, Alter BP. Aplastic anemia, acquired and inherited. Philadelphia: Saunders; 1994.

    Google Scholar 

  11. Sutherland R, Vincent PC, Raik E, Burgess K. Quinine-induced agranulocytosis: toxic effect of quinine bisulphate on bone marrow cultures in vitro. Br Med J. 1977;1(6061):605–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Young NS, Issaragrasil S, Chieh CW, Takaku F. Aplastic anaemia in the Orient. Br J Haematol. 1986;62(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  13. Antic M, Lautenschlager S, Itin PH. Eosinophilic fasciitis 30 years after - what do we really know? Report of 11 patients and review of the literature. Dermatology. 2006;213(2):93–101.

    Article  PubMed  Google Scholar 

  14. Hinterberger-Fischer M, Kier P, Forstinger I, Lechner K, Kornek G, Breyer S, et al. Coincidence of severe aplastic anaemia with multiple sclerosis or thyroid disorders. Report of 5 cases. Acta Haematol. 1994;92(3):136–9.

    Article  CAS  PubMed  Google Scholar 

  15. Schoettler ML, Nathan DG. The pathophysiology of acquired aplastic anemia: current concepts revisited. Hematol Oncol Clin North Am. 2018;32(4):581–94.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108(8):2509–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barrett AJ, Horowitz MM, Pollock BH, Zhang MJ, Bortin MM, Buchanan GR, et al. Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. N Engl J Med. 1994;331(19):1253–8.

    Article  CAS  PubMed  Google Scholar 

  18. Breatnach F, Chessells JM, Greaves MF. The aplastic presentation of childhood leukaemia: a feature of common-ALL. Br J Haematol. 1981;49(3):387–93.

    Article  CAS  PubMed  Google Scholar 

  19. Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009;147(1):43–70.

    Article  CAS  PubMed  Google Scholar 

  20. Bessler M, Fehr J. Fc III receptors (FcRIII) on granulocytes: a specific and sensitive diagnostic test for paroxysmal nocturnal hemoglobinuria (PNH). Eur J Haematol. 1991;47(3):179–84.

    Article  CAS  PubMed  Google Scholar 

  21. Sutherland DR, Kuek N, Davidson J, Barth D, Chang H, Yeo E, et al. Diagnosing PNH with FLAER and multiparameter flow cytometry. Cytometry B Clin Cytom. 2007;72(3):167–77.

    Article  PubMed  Google Scholar 

  22. Camitta BM, Thomas ED, Nathan DG, Santos G, Gordon-Smith EC, Gale RP, et al. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. Blood. 1976;48(1):63–70.

    Article  CAS  PubMed  Google Scholar 

  23. Camitta BM, Rappeport JM, Parkman R, Nathan DG. Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood. 1975;45(3):355–63.

    Article  CAS  PubMed  Google Scholar 

  24. Bacigalupo A, Hows J, Gluckman E, Nissen C, Marsh J, Van Lint MT, et al. Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT SAA working party. Br J Haematol. 1988;70(2):177–82.

    Article  CAS  PubMed  Google Scholar 

  25. Hochsmann B, Moicean A, Risitano A, Ljungman P, Schrezenmeier H. Supportive care in severe and very severe aplastic anemia. Bone Marrow Transplant. 2013;48(2):168–73.

    Article  CAS  PubMed  Google Scholar 

  26. Carpenter PA, Englund JA. How I vaccinate blood and marrow transplant recipients. Blood. 2016;127(23):2824–32.

    Article  CAS  PubMed  Google Scholar 

  27. Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016;172(2):187–207.

    Article  PubMed  Google Scholar 

  28. Samarasinghe S, Webb DK. How I manage aplastic anaemia in children. Br J Haematol. 2012;157(1):26–40.

    Article  CAS  PubMed  Google Scholar 

  29. Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof E, Bekassy A, et al. Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2007;92(1):11–8.

    Article  CAS  PubMed  Google Scholar 

  30. Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood. 2012;120(6):1185–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Peslak SA, Olson T, Babushok DV. Diagnosis and treatment of aplastic anemia. Curr Treat Options in Oncol. 2017;18(12):70.

    Article  Google Scholar 

  32. Yoshida N, Yagasaki H, Hama A, Takahashi Y, Kosaka Y, Kobayashi R, et al. Predicting response to immunosuppressive therapy in childhood aplastic anemia. Haematologica. 2011;96(5):771–4.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H, German Aplastic Anemia Study G. Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood. 2003;101(4):1236–42.

    Article  CAS  PubMed  Google Scholar 

  34. Scheinberg P, Wu CO, Nunez O, Young NS. Long-term outcome of pediatric patients with severe aplastic anemia treated with antithymocyte globulin and cyclosporine. J Pediatr. 2008;153(6):814–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fuhrer M, Rampf U, Baumann I, Faldum A, Niemeyer C, Janka-Schaub G, et al. Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood. 2005;106(6):2102–4.

    Article  PubMed  Google Scholar 

  36. Kamio T, Ito E, Ohara A, Kosaka Y, Tsuchida M, Yagasaki H, et al. Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group. Haematologica. 2011;96(6):814–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Saracco P, Quarello P, Iori AP, Zecca M, Longoni D, Svahn J, et al. Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up. Br J Haematol. 2008;140(2):197–205.

    Article  CAS  PubMed  Google Scholar 

  38. Bacigalupo A, Brand R, Oneto R, Bruno B, Socie G, Passweg J, et al. Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy--the European Group for Blood and Marrow Transplantation experience. Semin Hematol. 2000;37(1):69–80.

    Article  CAS  PubMed  Google Scholar 

  39. Socie G, Mary JY, Schrezenmeier H, Marsh J, Bacigalupo A, Locasciulli A, et al. Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT). Blood. 2007;109(7):2794–6.

    Article  CAS  PubMed  Google Scholar 

  40. 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(12):1818–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med. 2017;376(16):1540–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Champlin RE, Perez WS, Passweg JR, Klein JP, Camitta BM, Gluckman E, et al. Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens. Blood. 2007;109(10):4582–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Locatelli F, Bruno B, Zecca M, Van-Lint MT, McCann S, Arcese W, et al. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial. Blood. 2000;96(5):1690–7.

    CAS  PubMed  Google Scholar 

  44. Passweg JR, Socie G, Hinterberger W, Bacigalupo A, Biggs JC, Camitta BM, et al. Bone marrow transplantation for severe aplastic anemia: has outcome improved? Blood. 1997;90(2):858–64.

    CAS  PubMed  Google Scholar 

  45. Bacigalupo A, Locatelli F, Lanino E, Marsh J, Socie G, Maury S, et al. Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bone Marrow Transplant. 2005;36(11):947–50.

    Article  CAS  PubMed  Google Scholar 

  46. Dufour C, Veys P, Carraro E, Bhatnagar N, Pillon M, Wynn R, et al. Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT. Br J Haematol. 2015;171(4):585–94.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The author would like to thank pathologists Aarti Goswami and Stephanie Wright for assistance in providing bone marrow pictures for our patients.

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Authors and Affiliations

  1. Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, Ruby Memorial Hospital, West Virginia University, Morgantown, WV, USA

    Lubna S. Mehyar

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  1. Lubna S. Mehyar
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Correspondence to Lubna S. Mehyar .

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Editors and Affiliations

  1. Department of Pediatrics, University of Texas Health Science Center, San Antonio, TX, USA

    Deepak M. Kamat

  2. Department of Pediatrics, Division of Hematology-Oncology, The University of Texas Health Science Center, San Antonio, TX, USA

    Melissa Frei-Jones

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Mehyar, L.S. (2021). What Pediatricians Need to Know About Acquired Aplastic Anemia. In: Kamat, D., Frei-Jones, M. (eds) Benign Hematologic Disorders in Children. Springer, Cham. https://doi.org/10.1007/978-3-030-49980-8_27

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  • DOI: https://doi.org/10.1007/978-3-030-49980-8_27

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-49979-2

  • Online ISBN: 978-3-030-49980-8

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