SOVREMENNAYA PEDIATRIYA.2016.6(78):33-40; doi 10.15574/SP.2016.78.33 

Acquired aplastic anemia: special features of clinical, laboratory signs and course of the disease, treatment estimation 

Dorosh O. I., Tsymbalyuk-Voloshyn I. P., Polishchuk R. S., Vorobel O. I., Troyanovska O. O.,
Skoropad L. L., Kozlova O. I., Stepanyuk O. I., Seredych L. P., Myh A. M., Dubey L. Ya.,
Rachynska N. O., Siryk N. R.
Lviv Regional Council Public Institution «Western Ukrainian Specialized Children's Medical Centre», Ukraine
Danylo Halytskyy Lviv National Medical University, Ukraine

The authors analysed clinical, laboratory signs and course of acquired aplastic anemia (AAA) in 20 children and treatment effectiveness. It was ascertained that allogeneic bone marrow transplantation (AlloBMT) from family and unrelated donor is the most effective treatment approach. At the same time, symptomatic treatment is the least effective treatment approach. 14 children were treated according to the immunosuppressive program. A part of patients achieved antithymocyte globulin (rabbit) in the first course of immunosuppression, another part was treated with antilymphocyte globulin (horse). The first course of immunosuppressive treatment was effective only in 1/3 of patients. 75% of children improved after the second course of immunosuppression. Hemorrhagic and infectious complications caused the death of 1/3 of patients at the different periods of treatment. 14.3% of children in the course of immunosuppressive treatment manifested with secondary clonal diseases. In 7.1% of children the disease was resistant to the treatment.

Key words: children, acquired aplastic anemia, immunosuppressive treatment, bone marrow transplantation.

REFERENCES

1. Nagornaya NV, Bordyugova EV, Dudchak AP, Marchenko EN, Vilchevskaya EV. 2013. Aplastic anemia in children. Zdorovye rebyonka. 7(50).

2. Vinogradova MA, Klyasova HA, Mikhajlova EA et al. 2007. Infectious complications at the onset of aplastic anemia. Hematologiya i Transfuziologiya. 4: 16-21.

3. Kuzmina LA. 2001. Childhood Hematology. Medpress-inform, Moskow: 400.

4. Maschan AA. 1999. Treatment of acquired aplastic anemia in children. Det Doktor. 3: 31-35.

5. Maschan AA. 1999. Current treatment of aplastic anemia. VI Russian National Congress "Chelovek i lekarstvo", Apr.19-23: 330-344.

6. Mikhajlova EA, Ustinova EN, Klyasova HA. 2014. The combined immunosuppressive therapy in patients with aplastic anemia: efficacy of repeated courses of antithymocyte globulin. Hematologiya i Transfuziologiya. 4(59): 11-18.

7. Mikhajlova EA, Ustinova EN, Klyasova HA. 2008. Program treatment of patients with aplastic anemia. In: Program treatment of leukemia / By Cavchenko VH. GNC RAMN: 328-342.

8. On approving the protocols of care to children at a special “Pediatric hematology”. The order of the Ministry of Health of Ukraine, 20.07.2005, #364. http://www.moz.gov.ua.

9. Skvortsov VV, Tumarenko AV. 2010. Actual problems of treatment and diagnosis aplastic anemia. Terapevt. 3: 31-36.

10. Spichak II, Solovyova OS, Basharova EV. 2013. Results of treatment of patients with acquired aplastic anemia in oncohematological children's center of Chelyabinsk Region Children's Hospital for the last ten years. Pediatricheskij vestnik Yuzhnogo Urala. 2: 116-118.

11. Tichelli A, Schrezenmeier H, Socie G et al. 2011. A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G4CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation. Blood. 117(17): 4434—4441. https://doi.org/10.1182/blood-2010-08-304071; PMid:21233311

12. Griscelli-Bennaceur A, Gluckman E, Scrobohaci ML et al. 1995. Aplastic anemia and paroxysmal nocturnal hemoglobinuria: search for a pathogenetic link. Blood. 85(5): 1354—1363. PMid:7858265

13. Feng YH, Yen CJ, Huang WT et al. 2004. Clinical response of antilymphocyte globulin-based treatment in patients in taiwan with aplastic anemia: positive hepatitis C antibody may represent a response predictor. Int J Hematol. 79(2): 133—137. https://doi.org/10.1532/IJH97.A10306; PMid:15005340

14. Erlacher M, Strahm B. 2015. Missing Cells: Pathophysiology, Diagnosis, and Management of (Pan) Cytopenia in Childhood. Front Pediatr. 3: 64. https://doi.org/10.3389/fped.2015.00064; PMid:26217651 PMCid:PMC4500095

15. Pawelec K, Salamonowicz M, Panasiuk A et al. 2015. First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin. Adv Exp Med Biol. 836: 55—62. https://doi.org/10.1007/5584_2014_38; PMid:25310948

16. Yoshida N, Kobayashi R, Yabe H et al. 2014. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy. Haematologica. 99(12): 1784—1791. https://doi.org/10.3324/haematol.2014.109355; PMid:25193958 PMCid:PMC4258757

17. Marsh JC, Ball SE, Cavenagh J et al. 2009. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 147(1): 43—70. https://doi.org/10.1111/j.1365-2141.2009.07842.x; PMid:19673883

18. Yoshimi A, Niemeyer C, Baumann I et al. 2013. High incidence of Fanconi anaemia in patients with a morphological picture consistent with refractory cytopenia of childhood. Br J Haematol. 160(1): 109—111. https://doi.org/10.1111/bjh.12083; PMid:23043447

19. Fuhrer M, Rampf U, Baumann I et al. 2005. Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood. 106(6): 2102—2104. https://doi.org/10.1182/blood-2005-03-0874

20. Deyell RJ, Shereck EB, Milner RA, Schultz KR. 2011. Immunosuppressive therapy without hematopoietic growth factor exposure in pediatric acquired aplastic anemia. Pediatr Hematol Oncol. 28(6): 469—478. https://doi.org/10.3109/08880018.2011.568043; PMid:21707222

21. Gluckman E, Marmont A, Speck B, Gordon-Smith EC. 1984. Immunosuppressive treatment of aplastic anemia as an alternative treatment for bone marrow transplantation. For the Working Party on Severe Aplastic Anemia of the European Group for Bone Marrow Transplantation. Semin Hematol. 21: 11—19. PMid:6367052

22. Kaatsch P, Spix. C. 2004. Jahresbericht 2003. Hrsg. Deutsches Kinderkrebsregister. Mainz.

23. Korthof ET, Bekassy AN, Hussein AA. 2013. Management of acquired aplastic anemia in children. Bone Marrow Transplant. 48(2): 191—195. https://doi.org/10.1038/bmt.2012.235; PMid:23292240

24. Safadi R, Or R, Ilan Y et al. 2001. Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation. Bone Marrow Transplant. 27(2): 183—190. https://doi.org/10.1038/sj.bmt.1702749; PMid:11281388

25. Jeong DC, Chung NG, Cho B et al. 2014. Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children. Haematologica. 99(4): 664—671. https://doi.org/10.3324/haematol.2013.089268; PMid:24213150 PMCid:PMC3971076

26. Kim SY, Le Rademacher J, Antin JH et al. 2014. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation. Haematologica. 99(12): 1868—1875. https://doi.org/10.3324/haematol.2014.108977; PMid:25107891 PMCid:PMC4258748

27. Dufour C, Pillon M, Socie G et al. 2015. Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant. Br J Haematol. 169(4): 565—573. https://doi.org/10.1111/bjh.13297; PMid:25683884

28. Dufour C, Pillon M, Passweg J et al. 2014. Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 99(10): 1574—1581. https://doi.org/10.3324/haematol.2014.106096; PMid:25085353 PMCid:PMC4181253

29. Malhotra P, Bodh V, Guru Murthy GS et al. 2015. Outcomes of immunosuppressant therapy with lower dose of antithymocyte globulin and cyclosporine in aplastic anemia. Hematology. 20(4): 239—244. https://doi.org/10.1179/1607845414Y.0000000196; PMid:25181305

30. Forester CM, Sartain SE, Guo D et al. 2015. Pediatric aplastic anemia and refractory cytopenia: A retrospective analysis assessing outcomes and histomorphologic predictors. Am J Hematol. 90(4): 320—326. https://doi.org/10.1002/ajh.23937; PMid:25580823 PMCid:PMC4384448

31. Scheinberg P, Wu CO, Nunez O, Young NS. 2009. Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol. 144(2): 206—216. https://doi.org/10.1111/j.1365-2141.2008.07450.x; PMid:19036108 PMCid:PMC4149225

32. Chang MH, Kim KH, Kim HS et al. 2010. Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia. Eur J Haematol. 84(2): 154—159. https://doi.org/10.1111/j.1600-0609.2009.01378.x; PMid:19912311

33. Kosaka Y, Yagasaki H, Sano K et al. 2008. Prospective multicenter trial comparing repeated immunosuppressive therapy with stem4cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia. Blood. 111(3): 1054—1059. https://doi.org/10.1182/blood-2007-08-099168; PMid:17989314

34. Fuhrer M, Burdach S, Ebell W et al. 1998. Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group. Klin Padiatr. 210(4): 173—179. https://doi.org/10.1055/s-2008-1043875; PMid:9743949

35. Scheinberg P, Young NS. 2012. How I treat acquired aplastic anemia. Blood. 120(6): 1185-1196. https://doi.org/10.1182/blood-2011-12-274019; PMid:22517900 PMCid:PMC3418715

36. Dufour C, Veys P, Carraro E et al. 2015. Similar outcome of upfront4unrelated 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. 171(4): 585—594. https://doi.org/10.1111/bjh.13614; PMid:26223288

37. Marsh JC, Hows JM, Bryett KA et al. 1987. Survival after antilymphocyte globulin therapy for aplastic anemia depends on disease severity. Blood. 70: 1046—1052. PMid:3651599

38. Huaquan Wang, Meifeng Tu, Rong Fu et al. 2014. The Clinical and Immune Characteristics of Patients with Hepatitis-Associated Aplastic Anemia in China. PLoS One. 9(5): e98142. https://doi.org/10.1371/journal.pone.0098142; PMid:24845454 PMCid:PMC4028298

39. Zhao X, Zhang L et al. 2015. The role of paroxysmal nocturnal hemoglobinuria clones in response to immunosuppressive therapy of patients with severe aplastic anemia. Ann Hematol. 94(7): 1105—1110. https://doi.org/10.1007/s00277-015-2348-5; PMid:25784221

40. Yoshizato T. 2016. Chronologic analysis of clonal evolution in acquired aplastic anemia and sMDS. Rinsho Ketsueki. 57(4): 430—439. PMid:27169446

41. Young NS, Maciejewski J. 1997. The Pathophysiology of Acquired Aplastic Anemia. New England Journal of Medicine. 336(19): 1365—1372. https://doi.org/10.1056/NEJM199705083361906; PMid:9134878

42. Young NS. 2013. Current concepts in the pathophysiology and treatment of aplastic anemia. Hematology Am Soc Hematol Educ Program. 2013: 76—81. https://doi.org/10.1182/asheducation-2013.1.76; PMid:24319166