title: Standard dose and prolonged administration of azacitidine are associated with improved efficacy in a real-world group of patients with myelodysplastic syndrome or low blast count acute myeloid leukemia.
abstract: OBJECTIVE
  Azacitidine is the standard of care for higher-risk myelodysplastic syndromes (MDS). We evaluated factors affecting the outcome of azacitidine treatment in 196 'real-world' patients, retrospectively collected by two Italian cooperative groups.
  
  
  METHODS
  The study included 184 MDS and 12 low blast count acute myeloid leukemia (AML). Azacitidine was administered at the standard dose of 75 mg/m(2)/d for 7 d (SD) in 163 patients and 100 mg/d for 5-7 d in 33 patients.
  
  
  RESULTS
  After a median of 4.5 azacitidine cycles (range 7-15 cycles), 182 patients were evaluable for response. Nineteen percent achieved complete remission (CR), 17% partial remission (PR), and 21% hematological improvement (HI). The disease was stable or progressive in 29% and 14% of patients, respectively. The probability of response was significantly higher in patients who received the 75 mg/m(2)/7 d compared with 100 mg through 5-7 d dose (CR/PR/HI: 63 vs. 29%, P = 0.0005). Median overall survival was 17.1 months. Low MDS-CI and achievement of CR/PR/HI were significant predictors of survival in the multivariable analysis.
  
  
  CONCLUSIONS
  Our data show that maximal azacitidine efficacy is associated with the standard dose and with prolonged treatment, beyond 4-6 cycles, with the goal of also improving the 'quality' of response. Lower MDS-CI and IPSS-R scores, hematologic response and disease stability, are associated with longer survival. The risk of febrile events is highest during the first treatment cycles and is associated with active disease.
authors.affiliation: Hematology, Department of Biomedicine and Prevention, Università di Roma 'Tor Vergata', Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.affiliation: S. Eugenio Hospital, Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Niscola
authors.affiliation: Department of Statistical Sciences, Universita' La Sapienza, Rome, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Piciocchi
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Fianchi
authors.affiliation: Hematology, Department of Biomedicine and Prevention, Università di Roma 'Tor Vergata', Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Maurillo
authors.affiliation: MDS Registry of Basilicata, IRCCS-CROB, Rionero in Vulture (Pz), Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Pagano
authors.affiliation: MDS Registry of Basilicata, IRCCS-CROB, Rionero in Vulture (Pz), Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mansueto
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Criscuolo
authors.affiliation: Department of Hematology, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Aloe-Spiriti
authors.affiliation: Hematology, Department of Biomedicine and Prevention, Università di Roma 'Tor Vergata', Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.affiliation: Hematology, Department of Biomedicine and Prevention, Università di Roma 'Tor Vergata', Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.affiliation: S. Eugenio Hospital, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tendas
authors.affiliation: Sandro Pertini Hospital, Rome, Italy.
authors.forename: Anna Lina
authors.initials: AL
authors.lastname: Piccioni
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Zini
authors.affiliation: Department of Hematology, Universita' La Sapienza, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.affiliation: MDS Registry of Basilicata, S. Carlo Hospital, Potenza, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Filardi
authors.affiliation: MDS Registry of Basilicata, Ospedale Madonna della Grazie, Matera, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fragasso
authors.affiliation: Hospital San Giovanni Addolorata, Rome, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Fenu
authors.affiliation: Department of Hematology, Universita' La Sapienza, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D002452:Cell Count; D019468:Disease Management; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
keywords: AML; MDS; azacitidine