Clinical management of aplastic anemia

Expert Review of Hematology

Volumn 4, Issue 2, 2011, Pages 221-230

  Dezern, Amy E ^a   Brodsky, Robert A ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

anti thymocyte globulin; aplastic anemia; bone marrow failure; bone marrow transplantation; cyclosporine; hematopoietic stem cell transplantation; high dose cyclophosphamide; paroxysmal nocturnal hemoglobinuria

Indexed keywords

BUSULFAN; CYCLOPHOSPHAMIDE; CYCLOSPORIN; FLUDARABINE; GRANULOCYTE COLONY STIMULATING FACTOR; THYMOCYTE ANTIBODY;

APLASTIC ANEMIA; BACTERIAL INFECTION; BLOOD TRANSFUSION; BONE MARROW TRANSPLANTATION; DRUG EFFICACY; ERYTHROCYTE TRANSFUSION; GRAFT VERSUS HOST REACTION; GRANULOCYTE TRANSFUSION; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HLA SYSTEM; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; MYCOSIS; ORGAN DONOR; PRIORITY JOURNAL; RELAPSE; REVIEW; SUPPORT GROUP; THROMBOCYTE TRANSFUSION;

ANEMIA, APLASTIC; BONE MARROW TRANSPLANTATION; CYCLOPHOSPHAMIDE; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; TRANSPLANTATION CONDITIONING;

EID: 79955068933     PISSN: 17474086     EISSN: None     Source Type: Journal    
DOI: 10.1586/ehm.11.11     Document Type: Review

References (78)

1. Ehrlich P. [On the case of anemia with remarks on regenerative bone marrow changes]. Charite-Annalen 13, 301-309 (1888).
2. Nakanishi K, Taniguchi T, Ranganathan V et al. Interaction of FANCD2 and NBS1 in the DNA damage response. Nat. Cell Biol. 4(12), 913-920 (2002). (Pubitemid 35469420)
3. Uechi T, Nakajima Y, Chakraborty A, Torihara H, Higa S, Kenmochi N. Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia. Hum. Mol. Genet. 17(20), 3204-3211 (2008).
4. Chakraborty A, Uechi T, Higa S, Torihara H, Kenmochi N. Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response. PLoS One 4(1), e4152 (2009).
5. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108(8), 2509-2519 (2006).
6. Brodsky RA, Jones RJ. Aplastic anaemia. Lancet 365(9471), 1647-1656 (2005). (Pubitemid 40703909)
7. Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br. J. Haematol. 115(4), 1015-1022 (2001). (Pubitemid 34042927)
8. Brodsky RA, Mukhina GL, Li S et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am. J. Clin. Pathol. 114(3), 459-466 (2000). (Pubitemid 33049682)
9. Hall SE, Rosse WF. The use of monoclonal antibodies and flow cytometry in the diagnosis of paroxysmal nocturnal hemoglobinuria. Blood 87, 5332-5340 (1996). (Pubitemid 26189877)
10. Borowitz MJ, Craig FE, DiGiuseppe JA et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin. Cytom. 78(4), 211-230 (2010).
11. Mukhina GL, Buckley JT, Barber JP, Jones RJ, Brodsky RA. Multilineage glycosylphosphatidylinositol anchor deficient hematopoiesis in untreated aplastic anemia. Br. J. Haematol. 115, 476-482 (2001). (Pubitemid 34203519)
12. Matsui WH, Brodsky RA, Smith BD, Borowitz MJ, Jones RJ. Quantitative analysis of bone marrow CD34 cells in aplastic anemia and hypoplastic myelodysplastic syndromes. Leukemia 20(3), 458-462 (2006). (Pubitemid 43291744)
13. Orazi A, Albitar M, Heerema NA, Haskins S, Neiman RS. Hypoplastic myelodysplastic syndromes can be distinguished from acquired aplastic anemia by CD34 and PCNA immunostaining of bone marrow biopsy specimens. Am. J. Clin. Pathol. 107(3), 268-274 (1997). (Pubitemid 27090230)
14. Kim SY, Lee JW, Lee SE et al. The characteristics and clinical outcome of adult patients with aplastic anemia and abnormal cytogenetics at diagnosis. Genes Chromosomes Cancer 49(9), 844-850 (2010).
15. Williams DM, Lynch RE, Cartwright GE. Prognostic factors in aplastic anaemia. Clin. Haematol. 7(3), 467-474 (1978).
16. Kwon JH, Kim I, Lee YG et al. Clinical course of non-severe aplastic anemia in adults. Int. J. Hematol. 91(5), 770-775 (2010).
17. Laundy GJ, Bradley BA, Rees BM, Younie M, Hows JM. Incidence and specificity of HLA antibodies in multitransfused patients with acquired aplastic anemia. Transfusion 44(6), 814-825 (2004). (Pubitemid 38738408)
18. Killick SB, Win N, Marsh JC et al. Pilot study of HLA alloimmunization after transfusion with pre-storage leucodepleted blood products in aplastic anaemia. Br. J. Haematol. 97(3), 677-684 (1997). (Pubitemid 27261641)
19. Marsh J, Socie G, Tichelli A et al. Should irradiated blood products be given routinely to all patients with aplastic anaemia undergoing immunosuppressive therapy with anti-thymocyte globulin (ATG)? A survey from the European Group for Blood and MarrowTransplantation Severe Aplastic Anaemia Working Party. Br. J. Haematol. 150(3), 377-379 (2010).
20. Quillen K, Wong E, Scheinberg P et al. Granulocyte transfusions in severe aplastic anemia: an eleven-year experience. Haematologica 94(12), 1661-1668 (2009).
21. Marsh JC, Ganser A, Stadler M. Hematopoietic growth factors in the treatment of acquired bone marrow failure states. Semin. Hematol. 44(3), 138-147 (2007). (Pubitemid 47031223)
22. Gluckman E, Rokicka-Milewska R, Hann I et al. Results and follow-up of a Phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia. Br. J. Haematol. 119(4), 1075-1082 (2002). (Pubitemid 35463836)
23. Teramura M, Kimura A, Iwase S et al. Treatment of severe aplastic anemia with anti-thymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan. Blood 110(6), 1756-1761 (2007). (Pubitemid 47443885)
24. Gurion R, Gafter-Gvili A, Paul M et al. Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy-systematic review and meta-analysis. Haematologica 94(5), 712-719 (2009).
25. Socie G, Mary JY, Schrezenmeier H et al. Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT).Blood 109(7), 2794-2796 (2007). (Pubitemid 46482073)
26. Kojima S, Hibi S, Kosaka Y et al. Immunosuppressive therapy using anti-thymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood 96(6), 2049-2054 (2000).
27. Aytac S, Yildirim I, Ceyhan M et al. Risks and outcome of fungal infection in neutropenic children with hematologic diseases. Turk. J. Pediatr. 52(2), 121-125 (2010).
28. Aki ZS, Sucak GT, Yegin ZA, Guzel O, Erbas G, Senol E. Hematopoietic stem cell transplantation in patients with active fungal infection: not a contraindication for transplantation. Transplant Proc. 40(5), 1579-1585 (2008). (Pubitemid 351853225)
29. Valdez JM, Scheinberg P, Young NS, Walsh TJ. Infections in patients with aplastic anemia. Semin. Hematol. 46(3), 269-276 (2009).
30. Torres HA, Bodey GP, Rolston KV, Kantarjian HM, Raad II, Kontoyiannis DP. Infections in patients with aplastic anemia: experience at a tertiary care cancer center. Cancer 98(1), 86-93 (2003). (Pubitemid 36741130)
31. Moriyama B, Henning SA, Childs R et al. High-dose continuous infusion b-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections in immunocompromised patients. Ann. Pharmacother. 44(5), 929-935 (2010).
32. Socie G, Henry-Amar M, Bacigalupo A et al. Malignant tumors occuring after treatment of aplastic anemia. N. Engl. J. Med. 329, 1152-1157 (1993). (Pubitemid 23295457)
33. Locasciulli A, Oneto R, Bacigalupo 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 92(1), 11-18 (2007). (Pubitemid 46232653)
34. Lawler M, McCann SR, Marsh JC et al. Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA. Br. J. Haematol. 144(6), 933-945 (2009).
35. Sensenbrenner LL, Steele AA, Santos GW. Recovery of hematologic competence without engraftment following attempted bone marrow transplantation for aplastic anemia: report of a case with diffusion chamber studies. Exp. Hematol. 77(1), 51-58 (1977). (Pubitemid 8012454)
36. Thomas ED, Storb R, Giblett ER et al. Recovery from aplastic anemia following attempted marrow transplantation. Exp. Hematol. 4, 97-102 (1976).
37. Piccin A, McCann S, Socie G et al. Survival of patients with documented autologous recovery after SCT for severe aplastic anemia: a study by the WPSAA of the EBMT. Bone Marrow Transplant. 45(6), 1008-1013 (2010).
38. Schrezenmeier H, Passweg JR, Marsh JC et al. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 110, 1397-1400 (2007). (Pubitemid 47281442)
39. Storb R, Leisenring W, Anasetti C et al. Long-term follow-up of allogeneic marrow transplants in patients with aplastic anemia conditioned by cyclophosphamide combined with anti-thymocyte globulin. Blood 89(10), 3890-3891 (1997). (Pubitemid 27227118)
40. Kahl C, Leisenring W, Deeg HJ et al. Cyclophosphamide and anti-thymocyte globulin as a conditioning regimen for allogeneic marrow transplantation in patients with aplastic anaemia: a long-term follow-up. Br. J. Haematol. 130(5), 747-751 (2005). (Pubitemid 43906647)
41. Bacigalupo A. Bone marrow transplantation for severe aplastic anemia from HLA identical siblings. Haematologica 84(1), 2-4 (1999). (Pubitemid 29479375)
42. Champlin RE, Perez WS, Passweg JR et al. Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens. Blood 109(10), 4582-4585 (2007). (Pubitemid 46743430)
43. Al-Zahrani H, Nassar A, Al-Mohareb F et al. Fludarabine based conditioning chemotherapy for allogeneic hematopoietic stem cell transplantation in acquired severe aplastic anemia. Biol. Blood Marrow Transplant. DOI: 10.1016/j. bbmt.2010.08.013 (2010) (Epub ahead of print).
44. Srinivasan R, Takahashi Y, McCoy JP 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. 133(3), 305-314 (2006).
45. Bacigalupo A, Oneto R, Bruno B et al. Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow Transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation. Acta Haematol. 103(1), 19-25 (2000). (Pubitemid 30150902)
46. Deeg HJ, Amylon ID, Harris RE et al. Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation. Biol. Blood Marrow Transplant. 7(4), 208-215 (2001). (Pubitemid 32433247)
47. Margolis D, Camitta B, Pietryga D et al. Unrelated donor bone marrow transplantation to treat severe aplastic anaemia in children and young adults. Br. J. Haematol. 94(1), 65-72 (1996). (Pubitemid 26232541)
48. Passweg JR, Perez WS, Eapen M et al. Bone marrow transplants from mismatched related and unrelated donors for severe aplastic anemia. Bone Marrow Transplant. 37(7), 641-649 (2006).
49. Deeg HJ, O'Donnell M, Tolar J et al. Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy. Blood 108(5), 1485-1491 (2006). (Pubitemid 44316112)
50. Peinemann F, Grouven U, Kroger N, Pittler M, Zschorlich B, Lange S. Unrelated donor stem cell transplantation in acquired severe aplastic anemia: a systematic review. Haematologica 94(12), 1732-1742 (2009).
51. Viollier R, Socie G, Tichelli A et al. Recent improvement in outcome of unrelated donor transplantation for aplastic anemia. Bone Marrow Transplant. 41(1), 45-50 (2008).
52. Bacigalupo A, Socie G, Lanino E et al. Fludarabine, cyclophosphamide, anti-thymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party. Haematologica 95(6), 976-982 (2010).
53. May WS, Sensenbrenner LL, Burns WH et al. BMT for severe aplastic anemia using cyclosporin. Bone Marrow Transplant. 11, 459-464 (1993). (Pubitemid 23203894)
54. Ostronoff F, Ostronoff M, Souto-Maior AP et al. Prospective trial of mycophenolate mofetil-cyclosporine A prophylaxis for acute GVHD after G-CSF stimulated allogeneic bone marrow transplantation with HLA-identical sibling donors in patients with severe aplastic anemia and hematological malignancies. Clin. Transplant. 23(1), 33-38 (2009).
55. Yagasaki H, Kojima S, Yabe H et al. Tacrolimus/methotrexate versus cyclosporine/methotrexate as graft-versus-host disease prophylaxis in patients with severe aplastic anemia who received bone marrow transplantation from unrelated donors: results of matched pair analysis. Biol. Blood Marrow Transplant. 15(12), 1603-1608 (2009).
56. Luznik L, Engstrom LW, Iannone R, Fuchs EJ. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol. Blood Marrow Transplant. 8(3), 131-138 (2002). (Pubitemid 34285071)
57. Luznik L, O'Donnell PV, Symons HJ et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol. Blood Marrow Transplant. 14(6), 641-650 (2008). (Pubitemid 351664058)
58. DeZern AE, Luznik L, Fuchs EJ, Jones RJ, Brodsky RA. Post-transplantation cyclophosphamide for GVHD prophylaxis in severe aplastic anemia. Bone Marrow Transplant. DOI: 10.1038/bmt.2010.213 (2010) (Epub ahead of print).
59. Viollier R, Passweg J, Gregor M et al. Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia. Ann. Hematol. 84(1), 47-55 (2005). (Pubitemid 39618780)
60. Locasciulli A, Oneto R, Bacigalupo 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 92(1), 11-18 (2007). (Pubitemid 46232653)
61. Gafter-Gvili A, Ram R, Gurion R et al. ATG plus cyclosporine reduces all-cause mortality in patients with severe aplastic anemia-systematic review and meta-analysis. Acta Haematol. 120(4), 237-243 (2008).
62. Marsh J, Schrezenmeier H, Marin P et al. Prospective randomized multicenter study comparing cyclosporin alone versus the combination of anti-thymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party. Blood 93(7), 2191-2195 (1999). (Pubitemid 29153619)
63. Scheinberg P, Wu CO, Nunez O et al. Treatment of severe aplastic anemia with a combination of horse anti-thymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study. Haematologica 94(3), 348-354 (2009).
64. Alsultan A, Goldenberg NA, Kaiser N, Graham DK, Hays T. Tacrolimus as an alternative to cyclosporine in the maintenance phase of immunosuppressive therapy for severe aplastic anemia in children. Pediatr. Blood Cancer 52(5), 626-630 (2009).
65. 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. 133(6), 606-611 (2006). (Pubitemid 43742774)
66. Scheinberg P, Marte M, Nunez O, Young NS. Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine. Haematologica 95(7), 1075-1080 (2010).
67. Kao SY, Xu W, Brandwein JM et al. Outcomes of older patients (> or = 60 years) with acquired aplastic anaemia treated with immunosuppressive therapy. Br. J. Haematol. 143(5), 738-743 (2008).
68. Du HY, Pumbo E, Ivanovich J et al. TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements. Blood 113(2), 309-316 (2009).
69. Pavesi E, Avondo F, Aspesi A et al. Analysis of telomeres in peripheral blood cells from patients with bone marrow failure. Pediatr. Blood Cancer 53(3), 411-416 (2009).
70. Scheinberg P, Cooper JN, Sloand EM, Wu CO, Calado RT, Young NS. Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia. JAMA 304(12), 1358-1364 (2010).
71. Rosenfeld S, Follmann D, Nunez O, Young NS. Anti-thymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA 289(9), 1130-1135 (2003). (Pubitemid 37430327)
72. Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H. Anti-thymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood 101(4), 1236-1242 (2003). (Pubitemid 36182490)
73. Ohara A, Kojima S, Hamajima N et al. Myelodysplastic syndrome and acute myelogenous leukemia as a late clonalcomplication in children with acquired aplastic anemia. Blood 90(3), 1009-1013 (1997). (Pubitemid 27314134)
74. Brodsky RA, Sensenbrenner LL, Jones RJ. Complete remission in acquired severe aplastic anemia following high-dose cyclophosphamide. Blood 87, 491-494 (1996). (Pubitemid 26030304)
75. Brodsky RA, Sensenbrenner LL, Smith BD et al. Durable treatment-free remission following high-dose cyclophosphamide for previously untreated severe aplastic anemia. Ann. Intern. Med. 135, 477-483 (2001). (Pubitemid 32923564)
76. Brodsky RA, Chen AR, Dorr D et al. High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood 115(11), 2136-2141 (2010).
77. Baran DT, Griner PF, Klemperer MR. Recovery from aplastic anemia after treatment with cyclophosphamide. N. Engl. J. Med. 295, 1522-1523 (1976). (Pubitemid 8014699)
78. Tisdale JF, Dunn DE, Geller N et al. High-dose cyclophosphamide in severe aplastic anaemia: a randomised trial. Lancet 356, 1554-1559 (2000).