title: Improved Outcome of a Reduced Toxicity-Fludarabine, Cyclophosphamide, plus Antithymocyte Globulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia: Comparison of 2 Multicenter Prospective Studies.
abstract: Hematopoietic stem cell transplantation (HSCT) is a curative therapy for severe aplastic anemia (SAA); however, the optimal conditioning regimen for HSCT with an unrelated donor has not yet been defined. A previous study using a fludarabine (FLU), cyclophosphamide (Cy), and antithymocyte globulin (ATG) conditioning regimen (study A: 50 mg/kg Cy once daily i.v. on days -9, -8, -7, and -6; 30 mg/m(2) FLU once daily i.v. on days -5, -4, -3, and -2; and 2.5 mg/kg of ATG once daily i.v. on days -3, -2, and -1) demonstrated successful engraftment (100%) but had a high treatment-related mortality rate (32.1%). Therefore, given that Cy is more toxic than FLU, we performed a new phase II prospective study with a reduced-toxicity regimen (study B: 60 mg/kg Cy once daily i.v. on days -8 and -7; 40 mg/m(2) FLU once daily i.v. on days -6, -5, -4, -3, and -2; and 2.5 mg/kg ATG once daily i.v. on 3 days). Fifty-seven patients were enrolled in studies A (n = 28) and B (n = 29), and donor type hematologic recovery was achieved in all patients in both studies. The overall survival (OS) and event-free survival (EFS) rates of patients in study B was markedly improved compared with those in study A (OS: 96.7% versus 67.9%, respectively, P = .004; EFS: 93.3% versus 64.3%, respectively, P = .008). These data show that a reduced-toxicity conditioning regimen with FLU, Cy, and ATG may be an optimal regimen for SAA patients receiving unrelated donor HSCT.
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Taek
authors.initials: KT
authors.lastname: Hong
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyery
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Duk
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.affiliation: Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Nak Gyun
authors.initials: NG
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Hack Ki
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Kyung Nam
authors.initials: KN
authors.lastname: Koh
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Ho Joon
authors.initials: HJ
authors.lastname: Im
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Seo
authors.affiliation: Department of Pediatrics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Pediatrics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jun Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Pusan National University School of Medicine, Pusan, Republic of Korea.
authors.forename: Young Tak
authors.initials: YT
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Yeon Jung
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Ewha Woman's University School of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Ewha Woman's University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Ha
authors.initials: KH
authors.lastname: Ryu
authors.affiliation: Department of Pediatrics, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Inje University Haeundae Paik Hospital, Pusan, Republic of Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Park
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: hsahn@snu.ac.kr.
authors.forename: Hyo Seop
authors.initials: HS
authors.lastname: Ahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000401:mortality / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011446:Prospective Studies; D056910:Republic of Korea; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome; D061349:Unrelated Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Antithymocyte globulin (ATG); Cyclophosphamide; Fludarabine; Severe aplastic anemia; Thymoglobulin; Unrelated donor