International Journal of Hematology

, Volume 103, Issue 4, pp 461–468 | Cite as

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling

  • Takehiko MoriEmail author
  • Hideo Koh
  • Yasushi Onishi
  • Shinichi Kako
  • Makoto Onizuka
  • Heiwa Kanamori
  • Yukiyasu Ozawa
  • Chiaki Kato
  • Hiroatsu Iida
  • Ritsuro Suzuki
  • Tatsuo Ichinohe
  • Yoshinobu Kanda
  • Tetsuo Maeda
  • Shinji Nakao
  • Hirohito Yamazaki
Original Article


The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1–100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1–91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8–95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.


Aplastic anemia Allogeneic hematopoietic stem cell transplantation Cyclophosphamide Fludarabine 



The authors would like to thank all the physicians and data managers of each transplant center and the staff member of Data Center of Japan Society for Hematopoietic Stem Cell Transplantation.

Compliance with ethical standards

Conflict of interest



  1. 1.
    Armand P, Antin JH. Allogeneic stem cell transplantation for aplastic anemia. Biol Blood Marrow Transplant. 2007;13:505–16.CrossRefPubMedGoogle Scholar
  2. 2.
    Nakao S. Guest editorial: advances in the management of acquired aplastic anemia. Int J Hematol. 2013;97:551–2.CrossRefPubMedGoogle Scholar
  3. 3.
    Storb R, Etzioni R, Anasetti C, Appelbaum FR, Buckner CD, Bensinger W, et al. Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia. Blood. 1994;84:941–9.PubMedGoogle Scholar
  4. 4.
    Gluckman E, Horowitz MM, Champlin RE, Hows JM, Bacigalupo A, Biggs JC, et al. Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome. Blood. 1992;79:269–75.PubMedGoogle Scholar
  5. 5.
    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;130:747–51.CrossRefPubMedGoogle Scholar
  6. 6.
    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;36:947–50.CrossRefPubMedGoogle Scholar
  7. 7.
    Yabe H, Inoue H, Matsumoto M, Hamanoue S, Koike T, Ishiguro H, et al. Allogeneic haematopoietic cell transplantation from alternative donors with a conditioning regimen of low-dose irradiation, fludarabine and cyclophosphamide in Fanconi anaemia. Br J Haematol. 2006;134:208–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Resnick IB, Aker M, Shapira MY, Tsirigotis PD, Bitan M, Abdul-Hai A, et al. Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine-based preparative regimen. Br J Haematol. 2006;133:649–54.CrossRefPubMedGoogle Scholar
  9. 9.
    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;133:305–14.CrossRefPubMedGoogle Scholar
  10. 10.
    Gomez-Almaguer D, Vela-Ojeda J, Jaime-Perez JC, Gutierrez-Aguirre CH, Cantu-Rodriguez OG, Sobrevilla-Calvo P, et al. Allografting in patients with severe, refractory aplastic anemia using peripheral blood stem cells and a fludarabine-based conditioning regimen: the Mexican experience. Am J Hematol. 2006;81:157–61.CrossRefPubMedGoogle Scholar
  11. 11.
    Bacigalupo A, Socie G, Lanino E, Prete A, Locatelli F, Locasciulli A, et al. Fludarabine, cyclophosphamide, antithymocyte 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. 2010;95:976–82.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kohashi S, Mori T, Hashida R, Kato J, Saburi M, Kikuchi T, et al. Reduced-dose cyclophosphamide in combination with fludarabine and anti-thymocyte globulin as a conditioning regimen for allogeneic hematopoietic stem cell transplantation for aplastic anemia. Int J Hematol. 2015;101:102–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Maury S, Bacigalupo A, Anderlini P, Aljurf M, Marsh J, Socie G, et al. Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen. Haematologica. 2009;94:1312–5.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Takehiko Mori
    • 1
    Email author
  • Hideo Koh
    • 2
  • Yasushi Onishi
    • 3
  • Shinichi Kako
    • 4
  • Makoto Onizuka
    • 5
  • Heiwa Kanamori
    • 6
  • Yukiyasu Ozawa
    • 7
  • Chiaki Kato
    • 8
  • Hiroatsu Iida
    • 9
  • Ritsuro Suzuki
    • 10
  • Tatsuo Ichinohe
    • 11
  • Yoshinobu Kanda
    • 4
  • Tetsuo Maeda
    • 12
  • Shinji Nakao
    • 13
  • Hirohito Yamazaki
    • 13
  1. 1.Division of Hematology, Department of MedicineKeio University School of MedicineTokyoJapan
  2. 2.Hematology, Graduate School of MedicineOsaka City UniversityOsakaJapan
  3. 3.Department of Hematology and RheumatologyTohoku University HospitalMiyagiJapan
  4. 4.Division of Hematology, Saitama Medical CenterJichi Medical UniversitySaitamaJapan
  5. 5.Department of Hematology/OncologyTokai University School of MedicineKanagawaJapan
  6. 6.Department of HematologyKanagawa Cancer CenterKanagawaJapan
  7. 7.Department of HematologyJapanese Red Cross Nagoya First HospitalNagoyaJapan
  8. 8.Department of HematologyMeitetsu HospitalAichiJapan
  9. 9.Division of Cell TherapyNational Hospital Organization DAichiJapan
  10. 10.Department of HSCT Data ManagementNagoya University Graduate School of MedicineNagoyaJapan
  11. 11.Department of Hematology and Oncology, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan
  12. 12.Department of Hematology and OncologyOsaka University HospitalOsakaJapan
  13. 13.Cellular Transplantation BiologyKanazawa University Graduate School of Medical ScienceKanazawaJapan

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