title: Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial.
abstract: BACKGROUND
  Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old.
  
  
  METHODS
  We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine.
  
  
  RESULTS
  The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49-1.35) for survival and of 0.67 (95% CI, 0.42-1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22-1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22-1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40-3.42) and that for disease-free survival was 1.02 (99% CI, 0.40-2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65-2.27) for survival and 1.02 (95% CI, 0.56-1.85) for disease-free survival.
  
  
  CONCLUSIONS
  Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy.
authors.affiliation: Department of Tumorimmunology, Radboud University Medical Centre Nijmegen, Nijmegen, the Netherlands. t.deWitte@ncmls.ru.nl
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Anne
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Amin
authors.initials: A
authors.lastname: Belhabri
authors.forename: Michel
authors.initials: M
authors.lastname: Delforge
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.forename: Augustin
authors.initials: A
authors.lastname: Ferrant
authors.forename: Harald
authors.initials: H
authors.lastname: Biersack
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.forename: Joop H
authors.initials: JH
authors.lastname: Jansen
authors.forename: Eva
authors.initials: E
authors.lastname: Hellström-Lindberg
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovacsovics
authors.forename: Pierre
authors.initials: P
authors.lastname: Wijermans
authors.forename: Gert
authors.initials: G
authors.lastname: Ossenkoppele
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marie
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D016609:Neoplasms, Second Primary / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous