Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome

J Clin Oncol. 2005 Aug 20;23(24):5728-38. doi: 10.1200/JCO.2005.15.602. Epub 2005 Jul 11.


Purpose: This prospective phase II study evaluated toxicity, relapse rate, progression-free survival, and overall survival after allogeneic transplantation and conditioning with fludarabine, melphalan, and alemtuzumab in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Patients and methods: Fifty-two consecutive adults with AML and MDS were enrolled onto the study. Median age was 52 years (range, 17 to 71 years) and the majority of patients had high-risk disease, comorbidities, and/or modest reduction in performance status. Fifty-six percent of patients had unrelated or mismatched related donors.

Results: After a median follow-up of 18 months (range, 2 to 34 months), 1-year survival was 48% (95% CI, 34% to 61%), progression-free survival was 38% (95% CI, 25% to 52%), relapse rate was 27% (95% CI, 15% to 40%), and treatment-related mortality was 33% (95% CI, 20% to 46%). The cumulative probability of extensive chronic graft-versus-host disease (GVHD) was only 18% (95% CI, 8% to 40%); extensive chronic GVHD was only observed in recipients of unrelated donor transplants. Performance score and disease status were the major predictors of outcome. High-risk disease (ie, active AML or MDS with > 5% blasts) or even modest decreases in performance status were associated with poor outcomes. Patients with standard-risk leukemia (first or second complete remission) or MDS (< 5% blasts) had excellent outcomes despite unfavorable disease characteristics.

Conclusion: Fludarabine and melphalan combined with in vivo alemtuzumab is a promising transplantation regimen for patients with AML or MDS and low tumor burden. For patients with active disease, this regimen provides at best modest palliation. Despite a low incidence of GVHD, transplantation is still associated with considerable nonrelapse mortality in patients with decreased performance status.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Alemtuzumab
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / prevention & control
  • Humans
  • Leukemia, Myeloid / therapy*
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Myelodysplastic Syndromes / therapy*
  • Proportional Hazards Models
  • Prospective Studies
  • Remission Induction
  • Stem Cell Transplantation*
  • Transplantation Conditioning / methods*
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Alemtuzumab
  • Vidarabine
  • fludarabine
  • Melphalan