Skip to main content
SpringerLink
Log in

The role of paroxysmal nocturnal hemoglobinuria clones in response to immunosuppressive therapy of patients with severe aplastic anemia

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Whether paroxysmal nocturnal hemoglobinuria (PNH) clone in aplastic anemia (AA) is a prognostic factor to immunosuppressive therapy is a subject of debate. We evaluated hematological responses to immunosuppressive therapy (IST) in severe AA (SAA) patients with or without the presence of a PNH clone. In 97 SAA patients who received first-line IST between January and December 2011, 24 (24.7 %) had a PNH clone prior to treatment, with a median clone size of 7.82 % (range 1.19–45.46 %). The response rates to IST for patients with or without a PNH clone were 66.7 and 50.7 % (P < 0.172), 79.2 and 57.5 % (P < 0.057), and 79.2 and 67.1 % (P < 0.264) at 3, 6, and 12 months, respectively. Combined rate of complete and good partial responses differed between patients with or without a PNH clone: insignificantly at 3 months (41.7 vs. 21.9 %, P < 0.058), but significantly at 6 (66.7 vs. 31.5 %, P < 0.002) and 12 (75.0 vs. 46.6 %, P < 0.015) months. Multivariate analysis revealed that a pretreatment neutrophil count of >0.2 × 109/L is indicative of a better response, while the presence of a PNH clone is predictive to a higher combined rate of complete and good partial responses. This study demonstrated that the presence of a PNH clone could predict a better hematological response instead of a higher response rate in patients with SAA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Schrezenmeier H, Hertenstein B, Wagner B, Raghavachar A, Heimpel H (1995) A pathogenetic link between aplastic anemia and paroxysmal nocturnal hemoglobinuria is suggested by a high frequency of aplastic anemia patients with a deficiency of phosphatidylinositol glycan anchored proteins. Exp Hematol 23:81–87

    CAS  PubMed  Google Scholar 

  2. De Lord C, Tooze JA, Saso R, Marsh JC, Gordon-Smith EC (1998) Deficiency of glycosylphosphatidylinositol-anchored proteins in patients with aplastic anaemia does not affect response to immunosuppressive therapy. Br J Haematol 101:90–93

    Article  PubMed  Google Scholar 

  3. Scheinberg P, Marte M, Nunez O, Young NS (2010) Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine. Haematologica 95:1075–1080

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Sugimori C, Chuhjo T, Feng X et al (2006) Minor population of CD55-CD59-blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood 107:1308–1314

    Article  CAS  PubMed  Google Scholar 

  5. Kulagin A, Lisukov I, Ivanova M et al (2014) Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study. Br J Haematol 164:546–554

    Article  CAS  PubMed  Google Scholar 

  6. Yoshida N, Yagasaki H, Takahashi Y et al (2008) Clinical impact of HLA-DR15, a minor population of paroxysmal nocturnal haemoglobinuria-type cells, and an aplastic anaemia-associated autoantibody in children with acquired aplastic anaemia. Br J Haematol 142:427–435

    Article  CAS  PubMed  Google Scholar 

  7. Yamazaki H, Saito C, Sugimori N et al (2011) Thymoglobuline is as effective as lymphoglobuline in Japanese patients with aplastic anemia possessing increased glycosylphosphatidylinositol-anchored protein (GPI-AP) deficient cells. Blood (ASH Ann Meet Abstr) 118:1339

    Google Scholar 

  8. Socié G, Rosenfeld S, Frickhofen N, Gluckman E, Tichelli A (2000) Late clonal diseases of treated aplastic anemia. Semin Hematol 37:91–101

    Article  PubMed  Google Scholar 

  9. Azenishi Y, Ueda E, Machii T et al (1999) CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with aplastic anaemia. Br J Haematol 104:523–529

    Article  CAS  PubMed  Google Scholar 

  10. Dunn DE, Tanawattanacharoen P, Boccuni P et al (1999) Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med 131:401–408

    Article  CAS  PubMed  Google Scholar 

  11. International Agranulocytosis and Aplastic Anaemia Study (1987) Incidence of aplastic anaemia: relevance of diagnosis criteria. Blood 70:1718–1721

    Google Scholar 

  12. Timeus F, Crescenzio N, Lorenzati A et al (2010) Paroxysmal nocturnal haemoglobinuria clones in children with acquired aplastic anaemia: a prospective single centre study. Br J Haematol 150:483–485

    PubMed  Google Scholar 

  13. Afable MG 2nd, Shaik M, Sugimoto Y et al (2011) Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia. Haematologica 96:1269–1275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. 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 84:154–159

    Article  CAS  PubMed  Google Scholar 

  15. Yang WR, Xiong YY, Zhang L et al (2013) Predicting early response to immunosuppressive therapy in severe aplastic anemia by soluble transferrin receptor assay. Zhonghua Xue Ye Xue Za Zhi 34:709–713

    PubMed  Google Scholar 

  16. Camitta BM (2000) What is the definition of cure for aplastic anemia? Acta Haematol 103:16–18

    Article  CAS  PubMed  Google Scholar 

  17. Marsh JC, Ball SE, Cavenagh J et al (2009) Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 147:43–70

    Article  CAS  PubMed  Google Scholar 

  18. Scheinberg P, Wu CO, Nunez O, Young NS (2009) Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol 144:206–216

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Maciejewski JP, Follmann D, Nakamura R et al (2001) Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. Blood 98:3513–3519

    Article  CAS  PubMed  Google Scholar 

  20. Zeng W, Nakao S, Takamatsu H et al (1999) Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia. Blood 93:3008–3016

    CAS  PubMed  Google Scholar 

  21. Feng X, Scheinberg P, Wu CO et al (2011) Cytokine signature profiles in acquired aplastic anemia and myelodysplastic syndromes. Haematologica 96:602–606

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the National Public Health Benefit Research Foundation of China (Grant No. 201202017), the Important National Science and Technology Specific Projects of China (Grant No. 2011ZX09302-007-04), and the Natural Science Foundation of Tianjin (Grant No. 11JCYBJC10500). The authors would also like to acknowledge Dr. Huijun Wang for carefully conducting the PNH clone testing technique.

Authors’ contributions

FZ served as the principal investigator for this study. XZ wrote the paper and contributed to patient recruitment and statistical analysis. LZ, LJ, KZ, YL, GP, LY, YL, JL, HF, LS, and WY contributed to patient recruitment and treatment.

Conflict of interest

The authors declare no competing financial interests.

Ethical statement

This study was approved by the ethics committee of Blood Diseases Hospital, CAMS, and PUMC. All procedures followed were in accordance with the Helsinki Declaration of 1975, as revised in 2008. Patients provided written informed consent for data exploitation.

Author information

Authors and Affiliations

  1. Department of Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 288 Nanjing Road, Heping District, Tianjin, 300020, People’s Republic of China

    Xin Zhao, Li Zhang, Liping Jing, Kang Zhou, Yuan Li, Guangxin Peng, Lei Ye, Yang Li, Jianping Li, Huihui Fan, Lin Song, Wenrui Yang & Fengkui Zhang

Authors
  1. Xin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liping Jing
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guangxin Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lei Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jianping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Huihui Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Wenrui Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fengkui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fengkui Zhang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-015-2348-5

Keywords

Search

Navigation