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Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes

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Abstract

To investigate the long-term usefulness of immunosuppressive therapy (IST) for Japanese patients with lower-risk myelodysplastic syndromes, we retrospectively analyzed 29 MDS patients who were treated with cyclosporine A alone or with anti-thymocyte globulin at a single institute in Japan. A total of 58.6 % of patients showed hematological response to IST. Overall survival of all patients was 74.5 % at 5 years and 48.3 % at 10 years. The major adverse event was the elevation of creatinine level (grade 1 and 2). Eleven patients were still on IST at the time of analysis with, at least, some clinical benefits. Pneumonia was the most frequent cause of death (eight of 12 deaths), followed by bleeding (three of 12); most of the patients who died were non-responders. The presence of paroxysmal nocturnal hemoglobinuria–type cells was significantly associated with both response to IST and long-term survival by univariate analysis. The 10-year overall survival of responders (72.2 %) was significantly superior to that of non-responders (15.6 %, P < 0.0001). These results suggest that IST using cyclosporine A provides long-term benefit for Japanese patients with lower-risk MDS.

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References

  1. Aggarwal S, van de Loosdrecht. AA, Alhan C, Ossenkoppele GJ, Westers TM, Bontkes HJ. Role of immune responses in the pathogenesis of low-risk MDS and high-risk MDS: implications for immunotherapy. Br J Haematol. 2011;153:568–81.

    Article  PubMed  CAS  Google Scholar 

  2. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–88.

    PubMed  CAS  Google Scholar 

  3. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system (IPSS-R) for myelodysplastic syndromes. Blood. 2012;120:2454–65.

    Article  PubMed  CAS  Google Scholar 

  4. Biesma DH, van den Tweel JG, Verdonck LF. Immunosuppressive therapy for hypoplastic myelodysplastic syndrome. Cancer. 1997;79:1548–51.

    Article  PubMed  CAS  Google Scholar 

  5. Molldrem JJ, Caples M, Marvoudis D, Plante M, Young NS, Barrett AJ. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol. 1997;99:699–705.

    Article  PubMed  CAS  Google Scholar 

  6. Killick SB, Mufti G, Cavenagh JD, Mijovic A, Peacock JL, Gordon-Smith EC, et al. A pilot study of antithymocyte globulin (ATG) in the treatment of patients with ‘low -risk’ myelodysplasia. Br J Haematol. 2003;120:679–84.

    Article  PubMed  CAS  Google Scholar 

  7. Yazi S, Giles FJ, Tsimberidou AM, Estey EH, Kantarjian HM, O’Brien SA, et al. Antithymocyte globulin (ATG)—based therapy in patients with myelodysplastic syndromes. Leukemia. 2003;17:2101–6.

    Article  Google Scholar 

  8. Ornstein MC, Sekeres MA. Combination strategies in myelodysplastic syndromes. Int J Hematol. 2012;95:26–33.

    Article  PubMed  Google Scholar 

  9. Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C, et al. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med. 2002;137:156–63.

    Article  PubMed  Google Scholar 

  10. Lim ZY, Killick S, Germing U, Cavenagh J, Culligan D, Bacigalupo A, et al. Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin. Leukemia. 2007;21:1436–41.

    Article  PubMed  CAS  Google Scholar 

  11. Jonasova A, Neuwrirtova R, Cermak J, Vozobulova V, Mocikova K, Siskova M, et al. Cyclosporin A therapy in hypoplastic patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol. 1998;100:304–9.

    Article  PubMed  CAS  Google Scholar 

  12. Shimamoto T, Tohyama K, Okamoto T, Uchiyama T, Mori H, Tomonaga M, Asano Y, et al. Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan. Leuk Res. 2003;27:783–8.

    Article  PubMed  CAS  Google Scholar 

  13. Dixit A, Chatterjee T, Mishra P, Choudhary DR, Magapatra M, Saxena R, et al. Cyclosporin A in myelodysplastic syndrome: a preliminary report. Ann Hematol. 2005;84:565–8.

    Article  PubMed  CAS  Google Scholar 

  14. Ishikawa T, Tohyama K, Nakao S, Yoshida Y, Teramura M, Motoji T, et al. A prospective study of cyclosporine A treatment of patients with low-risk myelodysplastic syndrome: presence of CD55(−)CD59(−) blood cells predicts platelet response. Int J Hematol. 2007;86:150–7.

    Article  PubMed  CAS  Google Scholar 

  15. Broliden PA, Dahl IM, Hast R, Johansson B, Juvonen E, Kjeldsen L, et al. Antithymocyte globulin and cyclosporine A as combination therapy for low-risk non-sideroblastic myelodysplastic syndromes. Haematologica. 2006;91:667–70.

    PubMed  CAS  Google Scholar 

  16. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008;26:2505–11.

    Article  PubMed  Google Scholar 

  17. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189–99.

    PubMed  CAS  Google Scholar 

  18. Vardiman JW, Thiele J, Arber DA, Borowitz MJ, Porwit A, Harris NL, et al. The 2008 revision of the WHO classification of myeloid neoplasms and acute leukemia, rationale and important changes. Blood. 2009;114:937–51.

    Article  PubMed  CAS  Google Scholar 

  19. Iwanaga M, Furukawa K, Amenomori T, Mori H, Nakamura H, Fuchigami K, et al. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102:465–74.

    Article  PubMed  CAS  Google Scholar 

  20. Wang H, Chuhjo T, Yasue S, Omine M, Nakao S. Clinical significance of a minor population of paroxysmal nocturnal hemoglobulinemia—type cells in bone marrow failure syndrome. Blood. 2002;100:3897–902.

    Article  PubMed  CAS  Google Scholar 

  21. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419–25.

    Article  PubMed  CAS  Google Scholar 

  22. Kaplan L, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.

    Article  Google Scholar 

  23. Passweg JR, Giagounidis AAN, Simcock M, Aul C, Dobbelstein C, Stadler M, et al. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globlin plus cyclosporine with best supportive care—SAKK 33/99. J Clin Oncol. 2011;29:303–9.

    Article  PubMed  CAS  Google Scholar 

  24. Olnes MJ, Sloand EM. Targeting immune dysregulation in myelodysplastic syndromes. JAMA. 2011;305:814–9.

    Article  PubMed  CAS  Google Scholar 

  25. Kadia TM, Borthakur G, Garcia-Manero G, Faderl S, Jabbour E, Estrov Z, et al. Final results of the phase II study of rabbit anti-thymocyte globulin, ciclosporin, methylprednisone, and granulocyte colony-stimulating factor in patients with aplastic anaemia and myelodysplastic syndrome. Br J Haematol. 2012;157:312–20.

    Article  PubMed  CAS  Google Scholar 

  26. Sugimori C, Mochizuki K, Qi Z, Sugimori N, Ishiyama K, Kondo Y, et al. Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure. Br J Hematol. 2009;147:102–12.

    Article  CAS  Google Scholar 

  27. Saunthararajah Y, Nakamura R, Nam JM, Robyn J, Loberiza F, Maciejewski JP, et al. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood. 2002;100:1570–4.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Shinji Nakao and his colleagues at the Department Hematology of Kanazawa University for examining the presence of PNH-type cells. This study was partly supported by a Grant from the Ministry of Health, Labour and Welfare of Japan (H23-Nanchi-001).

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Authors and Affiliations

  1. Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Nagasaki, 852-8523, Japan

    Tomoko Hata, Hideki Tsushima, Maki Baba, Yoshitaka Imaizumi, Jun Taguchi, Daisuke Imanishi & Yasushi Miyazaki

  2. Transfusion and Cell Therapy Unit, Nagasaki University Hospital, Nagasaki University, Nagasaki, Nagasaki, Japan

    Kazuhiro Nagai

  3. Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Nagasaki, Japan

    Masao Tomonaga

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  1. Tomoko Hata
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  2. Hideki Tsushima
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  4. Yoshitaka Imaizumi
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  5. Jun Taguchi
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  9. Yasushi Miyazaki
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Correspondence to Tomoko Hata.

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Hata, T., Tsushima, H., Baba, M. et al. Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes. Int J Hematol 98, 687–693 (2013). https://doi.org/10.1007/s12185-013-1468-8

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  • DOI: https://doi.org/10.1007/s12185-013-1468-8

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