title: Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.
abstract: 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.
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tmori@a3.keio.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.affiliation: Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Koh
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Hospital, Miyagi, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Onishi
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kako
authors.affiliation: Department of Hematology/Oncology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.affiliation: Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan.
authors.forename: Heiwa
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Hematology, Meitetsu Hospital, Aichi, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kato
authors.affiliation: Division of Cell Therapy, National Hospital Organization D, Aichi, Japan.
authors.forename: Hiroatsu
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of HSCT Data Management, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Department of Hematology and Oncology, Osaka University Hospital, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
authors.affiliation: Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000150:complications / Q000628:therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology; D006680:HLA Antigens / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Allogeneic hematopoietic stem cell transplantation; Aplastic anemia; Cyclophosphamide; Fludarabine