title: Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia.
abstract: OBJECTIVE
  The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural.
  
  
  METHODS
  Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years).
  
  
  RESULTS
  The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation.
  
  
  CONCLUSIONS
  The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.
authors.affiliation: Department of Hematology, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Tauro
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.forename: Karl
authors.initials: K
authors.lastname: Peggs
authors.forename: Gulnaz
authors.initials: G
authors.lastname: Begum
authors.forename: Premini
authors.initials: P
authors.lastname: Mahendra
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
authors.forename: Judith
authors.initials: J
authors.lastname: Marsh
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
authors.forename: Anthony
authors.initials: A
authors.lastname: Goldstone
authors.forename: Ann
authors.initials: A
authors.lastname: Hunter
authors.forename: Asim
authors.initials: A
authors.lastname: Khwaja
authors.forename: Raj
authors.initials: R
authors.lastname: Chopra
authors.forename: Timothy
authors.initials: T
authors.lastname: Littlewood
authors.forename: Andrew
authors.initials: A
authors.lastname: Peniket
authors.forename: Anne
authors.initials: A
authors.lastname: Parker
authors.forename: Graham
authors.initials: G
authors.lastname: Jackson
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Mark
authors.initials: M
authors.lastname: Cook
authors.forename: Nigel
authors.initials: N
authors.lastname: Russell
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D012307:Risk Factors; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan