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Kim, Baik, Yoo, Joe, Park, Lee, Kang, Jang, Park, Choi, and Kim: Outcome of Severe Aplastic Anemia Treated with Immunosuppressive Therapy Compared with Bone Marrow Transplantation
Original Article

Korean J Hematol 2006;41(4):259-265.

Published online: 19 January 2006

DOI: https://doi.org/10.5045/kjh.2006.41.4.259

Outcome of Severe Aplastic Anemia Treated with Immunosuppressive Therapy Compared with Bone Marrow Transplantation

Hyoung Il Kim, M.D., Seung Hee Baik, M.D., Jun Hwan Yoo, M.D., Dai Yeol Joe, M.D., Jung Il Park, M.D., Hyun Woo Lee, M.D., Seok Yun Kang, M.D., Jun Ho Jang, M.D., Joon Seong Park, M.D., Jin Hyuk Choi, M.D., Hugh Chul Kim, M.D.

Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea

Correspondence to：Hugh Chul Kim, M.D. Department of Hematology-Oncology, Ajou University School of Medicine San 5, Wonchon-dong, Yeongtong-gu, Suwon 443-721, Korea Tel: +82-31-219-5989, Fax: +82-31-219-5983 E-mail: hughkim@ajou.ac.kr

Received 24 August 2006       Revised 20 September 2006       Accepted 18 October 2006

Copyright © 2006 Korean Society of Hematology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

The response rates and survival following allogeneic bone marrow transplantation (BMT) or immunosuppressive treatment were compared in severe aplastic anemia (SAA) and the prognostic factors related with survival identified.

Methods:

Medical data of SAA patients, treated with BMT or immunosuppressive therapy (IST) at the Ajou University Hospital, between January 1995 and December 2005, were retrospectively analyzed.

Results:

A total of 43 patients were evaluable; 18 (41.9%) were treated with IST (antithymocyte globulin plus cyclosporine A plus steroid) and 25 (58.1%) with allogeneic BMT. In the IST group, the response rate was 77.8% (2 complete and 12 partial remissions), with two treatment failures. As later complications, acute myeloid leukemia developed in 1 patient and myelodysplastic syndrome developed in 2. In the BMT group, the response rate was 92.0% (18 complete and 5 partial remissions) (P＜0.001). Six patients developed grade II to III acute graft-versus-host-disease (GVHD) and 3 developed chronic GVHD. The median survival time in all patients was 60.27 months, and the 5-year survival rates were 61.0 and 81.9% in the IST and BMT groups, respectively (P=0.144). The factors influencing the overall survival were an age under 40-years and a positive treatment response.

Conclusion:

This study shows that allogeneic BMT, compared to IST, resulted in good response andoverall survival rates in patients with SAA. However, the overall survival rate between the two groups was statistically insignificant. Our study suggests that younger age SAA patients, with HLA-matched BMT donors, may benefit more from allogeneic BMT.

Keywords: Severe aplastic anemia, Bone marrow transplantation, Immunosuppressive therapy

REFERENCES

1). Gale RP., Champlin RE., Feig SA., Fitchen JH. Aplastic anemia: biology and treatment. Ann Intern Med. 1981. 95:477–94.
crossref
2). Young NS. Aplastic anemia, myelodysplasia, and related bone marrow failure syndromes. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 16th ed.United States of America: McGraw-Hill Companies;2005. p. 617–26.
3). Brodsky RA., Jones RJ. Aplastic anaemia. Lancet. 2005. 365:1647–56.
crossref
4). Bagby GC., Lipton JM., Sloand EM., Schiffer CA. Marrow failure. Hematology Am Soc Hematol Educ Program. 2004. 318–36.
crossref
5). Maciejewski JP., Risitano AM. Aplastic anemia: management of adult patients. Hematology Am Soc Hematol Educ Program. 2005. 110–7.
crossref
6). Kim I., Yoon SS., Park S., Kim BK., Kim NK. The treatment of severe aplastic anemia: outcomes of bone marrow transplantation and immunosuppressive therapy in a single institution of Korea. J Korean Med Sci. 2003. 18:365–71.
crossref
7). Sohn HJ., Jang GD., Shin YR, et al. Survival according to treatment modalities in 137 patients with aplastic anemia. Korean J Hematol. 2003. 38:1–7.
8). Ahn MJ., Choi JH., Lee YY, et al. Outcome of adult severe or very severe aplastic anemia treated with immunosuppressive therapy compared with bone marrow transplantation: multicenter trial. Int J Hematol. 2003. 78:133–8.
crossref
9). Young NS. Acquired aplastic anemia. Ann Intern Med. 2002. 136:534–46.
crossref
10). Frickhofen N., Rosenfeld SJ. Immunosuppressive treatment of aplastic anaemia with antithymocyte globulin and cyclosporine. Semin Hematol. 2000. 37:56–68.
11). Mehta J., Singhal S. Graft failure: diagnosis and management. Barrett J, Treleaven J, editors. The clinical practice of stem-cell transplantation. Oxford, England: Isis Medical Media;1998. p. 645–58.
12). Camitta BM., Storb R., Thomas ED. Aplastic anemia (first of two parts): pathogenesis, diagnosis, treatment, and prognosis. N Engl J Med. 1982. 306:645–52.
13). Marsh JC. Management of acquired aplastic anaemia. Blood Rev. 2005. 19:143–51.
crossref
14). Marsh J., Schrezenmeier H., Marin P, et al. Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte 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. 1999. 93:2191–5.
crossref
15). Gluckman E., Esperou-Bourdeau H., Baruchel A, et al. Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia. Blood. 1992. 79:2540–6.
crossref
16). Frickhofen N., Heimpel H., Kaltwasser JP., Schrezenmeier H. German Aplastic Anemia Group. Antithymocyte globulin with or without cyclosporin A; 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood. 2003. 101:1236–42.
crossref
17). 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. 289:1130–5.
18). Bacigalupo A., Brand R., Oneto R, 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. 37:69–80.
19). Socie G., Henry-Amar M., Bacigalupo A, et al. Malignant tumors occurring after treatment of aplastic anemia, for The European Bone Marrow Transplan-tation–Severe Aplastic Anemia Working Party. N Engl J Med. 1993. 329:1152–7.
20). Ades L., Mary JY., Robin M, et al. Long-term outcome after bone marrow transplantation for severe aplastic anemia. Blood. 2004. 103:2490–7.
crossref
21). Horowitz MM. Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. Semin Hematol. 2000. 37:30–42.
crossref
22). Margolis DA., Casper JT. Alternative-donor hematopoietic stem-cell transplantation for severe aplastic anemia. Semin Hematol. 2000. 37:43–55.
crossref
23). Deeg HJ., Leisenring W., Storb R, et al. Long-term outcome after marrow transplantation for severe aplastic anemia. Blood. 1998. 91:3637–45.
crossref
24). Bacigalupo A., Hows J., Gluckman E, 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. 70:177–82.
crossref

Fig. 1
Kaplan-Meier survival according to treatment modalities.
kjh-41-259f1.tif
Table 1.
Patient characteristics
  Immunosuppressive therapy no. (%) (n=18, 41.9%) BMT no. (%) (n=25, 58.1%) P
Age (year) ＜0.001
  ＜40 4 (22.2) 19 (76.0)  
  ≥40 14 (77.8) 6 (24.0)  
Sex 0.027
  Male 4 (22.2) 14 (56.0)  
  Female 14 (77.8) 11 (44.0)  
Grade 0.349
  SAA 13 (72.2) 21 (84.0)  
  vSAA 5 (27.8) 4 (16.0)  
ANC/mm3 0.24∗
  0～199 4 (22.2) 4 (16.0)  
  200～499 8 (44.4) 3 (12.0)  
  ≥500 6 (33.3) 18 (72.0)  
Platelet count/mm3 0.408∗
  0～19,000 14 (77.8) 21 (84.0)  
  20,000～49,000 3 (16.7) 4 (16.0)  
  ≥50,000 1 (5.6)    
Reticulocyte count 0.929∗
  0～0.99% 12 (75.0) 14 (73.7)  
  1.0～5.0% 4 (25.0) 5 (26.3)  
  Missing 2 6  
Etiology 0.942∗
  Idiopathic 16 (88.9) 23 (92.0)  
  Drug 1 (5.6) 1 (4.0)  
  Hepatitis 1 (5.6) 1 (4.0)  
CD34+ cell/kg
  0～1.99 ∗106   2 (8.0)  
  2.0～4.99 ∗106   5 (20.0)  
  ≥5.0 ∗106   18 (72.0)  
Nucleated marrow cell/kg
  0～4.99 ∗108   9 (36.0)  
  ≥5.0 ∗108   16 (64.0)  

P value by χ2 test except as indicated.

∗ P value by log-likelihood ratio test.

Abbreviations: SAA, severe aplastic anemia; vSAA, very severe aplastic anemia; BMT, bone marrow transplantation; ANC, absolute neutrophil count.

Table 2.
Treatment outcome
  Immunosuppressive therapy no. (%) (n=18, 41.9%) BMT no. (%) (n=25, 58.1%) P
Response ＜0.001∗
  Complete response 2 (11.1) 18 (72)  
  Partial response 12 (66.7) 5 (20.0)  
  No response 4 (22.2) 2 (8.0)  
Early death － 1 (4)  
Primary graft failure － －  
Secondary graft failure － 4 (16)  
Relapse 2 (11.1) 1 (4)  
Death 6 (33.3) 4 (16) 0.184
Cause of death      
  Sepsis   3  
  Hemorrhage 3    
  Hepatic failure 1    
GVHD      
  Acute GVHD   6 (24)  
  Chronic GVHD   3 (12)  
Long term complication      
  AML 1 －  
  MDS 2 －  
  PNH － －  

P value by χ test except as indicated.

∗P value by log-likelihood ratio test.

Abbreviations: GVHD, graft versus host disease; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; PNH, paroxysmal nocturnal hemoglobinuria.

Table 3.
Univariate analysis of factors influencing overall survival
Factor Overall survival rate (%) P∗
Response ＜0.0001
  Complete or partial response 84.21  
  No 20.00  
Grade 0.3513
  SAA 73.53  
  VSAA 88.89  
Age group, year 0.0043
  ＜40 91.30  
  ≥40 60.0  
Sex 0.4712
  Male 72.22  
  Female 80.00  
ANC/mm3 0.0076
  0～199 75.00  
  200～499 45.45  
  ≥500 91.67  
Platelet count/mm3 0.0008
  0～19,000 74.29  
  20,000～49,000 100  
  ≥50,000 0  
Reticulocyte count (%) 0.8384
  ＜1 80.77  
  ≥1 77.78  

∗P value by log-likelihood ratio test.

Table 4.
Multivariate analysis of factors influencing overall survival
Factor Reference group B SE df P Exp (B) (95% CI∗)
Sex Male 0.244 0.969 1 0.801 1.277 (0.191～8.523)
Age ≤40 2.974 1.288 1 0.021 19.567 (1.567～244.37)
Disease grade SAA －0.769 1.176 1 0.513 0.463 (0.046～4.648)
Reticulocyte count 1% 0.048 1.342 1 0.972 1.049 (0.076～14.555)
Treatment type BMT －0.567 0.970 1 0.559 0.567 (0.085～3.794)
Response CR, PR 3.231 1.177 1 0.006 25.315 (2.521～254.23)

∗CI indicates confidence interval.

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