title: Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure.
abstract: OBJECTIVE
  Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described.
  
  
  METHODS
  Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program).
  
  
  RESULTS
  The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care.
  
  
  CONCLUSIONS
  Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population.
authors.affiliation: Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prébet
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gore
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Claude
authors.initials: C
authors.lastname: Gardin
authors.forename: Raphael
authors.initials: R
authors.lastname: Itzykson
authors.forename: Sylvain
authors.initials: S
authors.lastname: Thepot
authors.forename: François
authors.initials: F
authors.lastname: Dreyfus
authors.forename: Odile Beyne
authors.initials: OB
authors.lastname: Rauzy
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.forename: Lionel
authors.initials: L
authors.lastname: Adès
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesnel
authors.forename: C L
authors.initials: CL
authors.lastname: Beach
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D017211:Treatment Failure
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine