title: Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine.
abstract: OBJECTIVE
  We conducted a phase III randomized clinical trial to compare two myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) in patients with leukemia and myelodysplastic syndrome.
  
  
  METHODS
  After randomization, 64 patients received busulfan (3.2 mg/kg per day × 4 days) plus cyclophosphamide (60 mg/kg per day × 2 days; BuCy), and 62 patients received busulfan (same dose and schedule) plus fludarabine (30 mg/m(2) per day × 5 days; BuFlu).
  
  
  RESULTS
  The median age was 41 years (range, 17 to 59 years). Five patients in the BuFlu arm experienced graft failure (primary, n = 1; secondary, n = 4). At 4 weeks after HCT, the median percentage of recipient hematopoietic chimerism was significantly greater in the BuFlu arm (0% v 5.5%; P < .001), and complete donor chimerism was greater in the BuCy arm (97.2% v 44.4%; P < .001). Severe (grade 3 or higher) infection and gastrointestinal adverse events were significantly more common in the BuCy arm, but the frequencies of hepatic adverse events were similar in the two arms. Nonrelapse mortality was similar in the two arms, but the BuCy arm had better overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS; OS at 2 years, 67.4% v 41.4%, P = .014; RFS, 74.7% v 54.9%, P = .027; EFS, 60.7% v 36.0%, P = .014).
  
  
  CONCLUSIONS
  Our results indicate that the BuFlu regimen is not a suitable replacement for the BuCy regimen in young adults who are eligible for myeloablative conditioning therapy for allogeneic HCT.
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jhlee3@amc.seoul.kr
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Joo
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.forename: Hun Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Gyeong-Won
authors.initials: GW
authors.lastname: Lee
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Jae-Hoo
authors.initials: JH
authors.lastname: Park
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Bae
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Sung-Doo
authors.initials: SD
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005759:Gastroenteritis / Q000209:etiology; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine