Aplastic Anemia

Hoon Kook

doi:10.5124/jkma.2006.49.10.885

Journal List > J Korean Med Assoc > v.49(10) > 1080698

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Kook: Aplastic Anemia

Special Issue

Anemia

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2006; 49(10): 885-896.

Published online: 31 October 2006

DOI: https://doi.org/10.5124/jkma.2006.49.10.885

Aplastic Anemia

Hoon Kook, MD

Department of Pediatrics, Chonnam National University Medical School, Korea. hoonkook@chonnam.ac.kr

Abstract

Aplastic anemia (AA) is a rare hematopoietic stem-cell disorder that results in pancytopenia and hypocellular bone marrow. The pathophysiology of acquired AA is immune-mediated in most cases. Activated type 1 cytotoxic T cells mediate the destruction of hematopoietic stem cells. The aberrant immune response and deficiencies in hematopoietic cells is now elucidated by molecular studies. In recent days, either stem cell transplant or immunosuppressive drug therapy with better supportive care has greatly improved the outcomes of patients with otherwise fatal disease. Combined immunosuppression with antithymocyte globulins and cyclosporine are effective in restoring blood counts in the majority of patients, but relapse and clonal evolution remain problematic. Allogeneic stem cell transplantation from matched sibling donors is curative in the great majority of young patients with severe AA. However, the results in patients who are older or lack family donors have room for improvement. Recent transplant results from alternative donors using a variety of conditioning regimens to enhance engraftment have been promising, especially in certain pediatric series.

Keywords: Aplastic anemia, Immunosuppression, Stem cell transplantation

Figures and Tables

Table 1

Etiologic classification of acquired aplastic anemia

Table 2

Combined immunosuppressive therapy for severe aplastic anemia

^*With androgens and+/-G-CSF

Table 3

Allogeneic sibling stem cell transplantation for severe aplastic anemia

EBMT, European Group for Bone Marrow Transplant; IBMTR; International Blood and Marrow Transplant Registry

^*GVHD, graft-versus-host disease; results are generally for grades II-IV diseases

Table 4

Alternative donor stem cell transplantation for severe aplastic anemia

IBMTR, International Blood and Marrow Transplant Registry

MUD, matched unrelated donor; MMUD, mismatched unrelated donor; Cy, cyclophosphamide; ATG, anti-thymocyte globulin; TBI, total body irradiation; LFI, limited filed irradiation; Flu, fludarabine

References

1. Jeong DC, Kang IJ, Koo HH, Kook H, Kim SY, Kim SK, et al. Epidemiology and clinical outcome in children with aplastic anemia in Korea: Retrospective study. Korean J Pediatr Hematol-Oncol. 2004. 11:137–152.

2. Young NS. Young NS, Gerson SL, High K, editors. Acquired aplastic anemia. Clinical Hematology. 2006. Philadelphia: Elsevier;136–157.

3. Sutton JF, Stacey M, Kearns WG, Rieg TS, Young NS, Liu JM. Increased risk for aplastic anemia and myelodysplastic syndrome in individuals lacking glutathione S-transferase genes. Pediatr Blood Cancer. 2004. 42:122–126.

4. Lu J, Basu A, Melenhorst J, Young NS, Brown KE. Analysis of T-cell repertoire in hepatitis-associated aplastic anemia. Blood. 2004. 103:4588–4593.

5. Maciejewski JP, Risitano A, Kook H, Zeng W, Chen G, Young NS. Immune pathophysiology of aplastic anemia. Int J Hematol. 2002. 76:Suppl 1. 207–214.

6. Kook H, Zeng W, Guibin C, Kirby M, Young NS, Maciejewski JP. Increased cytotoxic T cells with effector phenotype in aplastic anemia and myelodysplasia. Exp Hematol. 2001. 29:1270–1277.

7. Young NS. Hematopoietic cell destruction by immune mechanisms in acquired aplastic anemia. Semin Hematol. 2003. 37:3–14.

8. Kook H. Aplastic Anemia: Its Immune Pathophysiology. J Korean Pediatr Soc. 2002. 45:948–954.

9. Zeng W, Miyazato A, Chen G, Kajigaya S, Young NS. Interferon-γ-induced gene expression in CD34 cells: Identification of pathologic cytokine-specific signature profiles. Blood. 2006. 107:167–175.

10. Kook H, Risitano AM, Zeng W, Wlodarski M, Lottemann C, Nakamura R, et al. Changes in T-cell receptor Vβ repertoire in aplastic anemia: effects of different immunosuppressive regimens. Blood. 2002. 99:3668–3675.

11. Risitano AM, Maciejewski JP, Green S, Plasilova M, Zeng W, Young NS. In vivo dominant immune responses in aplastic anemia. Molecular tracking of putative pathogenic T cell clones by TCR β-CDR3 sequencing. Lancet. 2004. 364:355–364.

12. Wlodarski MW, Gondek LP, Nearman ZP, Plasilova M, Kalaycio M, Maciejewski JP. Molecular strategies for detection and quantitation of clonal cytotoxic T cell responses in aplastic anemia and myelodysplastic syndrome. Blood. 2006. 108:Epub ahead of print.

13. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006. 108:Epub ahead of print.

14. Lee JJ, Kook H, Chung IJ, Na JA, Park MR, Hwang TJ, et al. Telomere length changes in patients with aplastic anaemia. Br J Haematol. 2001. 112:1025–1030.

15. Hirano N, Butler MO, Von Bergwelt-Baildon MS, Maecker B, Schultze JL, O'Connor KC, et al. Autoantibodies frequently detected in patients with aplastic anemia. Blood. 2003. 102:4567–4575.

16. Young NS. Paroxysmal nocturnal hemoglobinuria: current issues in pathophysiology and treatment. Curr Hematol Rep. 2005. 4:103–109.

17. Kojima S, Ohara A, Tsuchida M, Kudoh T, Hanada R, Okimoto Y, et al. Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children. Blood. 2002. 100:786–790.

18. Marsh JC, Ball SE, Darbyshire P, Gordon-Smith EC, Keidan AJ, Martin A, et al. British Committee for Standards in Haematology. Guidelines for the diagnosis and management of acquired aplastic anaemia. Br J Haematol. 2003. 123:782–801.

19. Kook H. Aplastic Anemia. Korean J Pediatr. 2004. 47:Suppl 2. S242–S256.

20. Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H. Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood. 2003. 101:1236–1242.

21. Bacigalupo A, Bruno B, Saracco P, Di Bona E, Locasciulli A, Locatelli F, et al. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO). Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. Blood. 2000. 95:1931–1934.

22. Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003. 289:1130–1135.

23. Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M, Mugishima H, et al. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood. 2000. 96:2049–2054.

24. Scheinberg P, Nunez O, Wu C, Young NS. Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil. Br J Haematol. 2006. 133:606–611.

25. Brodsky RA, Chen A, Dorr DM, Brodsky I, Jones RJ. High dose cyclophosphamide (CY) for severe aplastic anemia (SAA): safely and long-term follow-up [abstract]. Blood. 2005. 106:Suppl 1. 41a–42a.

26. Di Bona E, Rodeghiero F, Bruno B, Gabbas A, Foa P, Locasciulli A, et al. Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Br J Haematol. 1999. 107:330–334.

27. Maciejewski JP, Sloand EM, Nunez O, Boss C, Young NS. Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood. 2003. 102:3584–3586.

28. Passweg JR, Perez WS, Eapen M, Camitta BM, Gluckman E, Hinterberger W, et al. Bone marrow transplants from mismatched related and unrelated donors for severe aplastic anemia. Bone Marrow Transplant. 2006. 37:641–649.

29. 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. 96:1690–1697.

30. Kim HJ, Park CY, Park YH, Kim YJ, Kim DW, Min WS, et al. Successful allogeneic hematopoietic stem cell transplantation using triple agent immunosuppression in severe aplastic anemia patients. Bone Marrow Transplant. 2003. 31:79–86.

31. Kahl C, Leisenring W, Deeg HJ, Chauncey TR, Flowers ME, Martin PJ, et al. Cyclophosphamide and antithymocyte globulin as a conditioning regimen for allogeneic marrow transplantation in patients with aplastic anaemia: a long-term follow-up. Br J Haematol. 2005. 130:747–751.

32. Srinivasan R, Takahashi Y, McCoy JP, Espinoza-Delgado I, Dorrance C, Igarashi T, et al. Overcoming graft rejection in heavily transfused and allo-immunised patients with bone marrow failure syndromes using fludarabine-based haematopoietic cell transplantation. Br J Haematol. 2006. 133:305–314.

33. Horowitz MM. Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. Semin Hematol. 2000. 37:30–42.

34. Kojima S, Matsuyama T, Kato S, Kigasawa H, Kobayashi R, Kikuta A, et al. Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood. 2002. 100:799–803.

35. Deeg HJ, O'donnell M, Tolar J, Agarwal R, Harris RE, Feig S, et al. Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy. Blood. 2006. 108:1485–1491.

36. 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. 36:947–950.

37. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR, et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med. 1998. 339:1565–1577.

38. Kook H, Baek HJ, Hwang TJ, Koo HH, Yoo KH, Sung KW, et al. Unrelated donor umbilical cord blood transplantation in children with acquired aplastic anemia. Korean experience of 12 cases. Blood. 2006. submitted.

TOOLS

Similar articles