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