title: Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
abstract: BACKGROUND
  Fludarabine plus busulfan (FB) and fludarabine plus melphalan (FM) are 2 widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (allo-SCT).
  
  
  METHODS
  The current survey compared transplantation outcomes for a cohort of 394 acute myeloid leukemia (AML) patients given bone marrow or peripheral blood stem cells from human leukocyte antigen-identical siblings after FB (n = 218) or FM (n = 176). Patients given manipulated grafts and those given T-cell-depleting agents (anti-thymocyte globulins or alemtuzumab) were not included.
  
  
  RESULTS
  At the time of transplantation, 266 patients (68%) were experiencing their first complete remission (CR), 69 (18%) were experiencing a later CR, and 59 (15%) had advanced disease. The incidences of acute and chronic graft-versus-host disease were similar in the 2 groups of patients. The 2-year relapse incidence (RI), nonrelapse mortality (NRM) rate, leukemia-free survival (LFS) rate, and overall survival (OS) rate were 31% ± 3%, 18% ± 3%, 51% ± 4%, and 54% ± 4%, respectively, for FB patients and 20% ± 3% (P = .007), 20% ± 3% (P = .4), 60% ± 4% (P = .08), and 62% ± 4% (P = .2), respectively, for FM patients. Among FB patients given intravenous busulfan (n = 81), the 2-year RI, NRM, LFS, and OS rates were 26% ± 5% (P = .43 vs FM patients), 25% ± 6% (P = .18), 49% ± 7% (P = .07), and 54% ± 7% (P = .13), respectively. In multivariate analyses, FM was associated with a lower RI (hazard ratio [HR], 0.5; P = .01) and a trend toward higher NRM (HR, 1.6; P = .1) with similar LFS (HR, 0.8; P = .2) and OS (HR, 0.9; P = .6).
  
  
  CONCLUSIONS
  These results suggest that although FM provides better AML control than FB as an RIC regimen for allo-SCT, the 2 regimens provide similar survival. Multicenter randomized studies are needed to confirm these findings.
authors.affiliation: Department of Hematology, University of Liege, Liege, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.forename: Andy
authors.initials: A
authors.lastname: Peniket
authors.forename: Pavel
authors.initials: P
authors.lastname: Jindra
authors.forename: Boris
authors.initials: B
authors.lastname: Afanasyev
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Eric
authors.initials: E
authors.lastname: Deconinck
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008212:Lymphocyte Depletion; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan
keywords: acute myeloid leukemia (AML); busulfan; fludarabine; graft-versus-host disease (GVHD); melphalan; reduced-intensity conditioning (RIC); transplantation