title: Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications.
abstract: BACKGROUND
  The MDS-IWG and NCCN currently endorse both FAB and WHO classifications of MDS and AML, thus allowing patients with 20-30 % bone marrow blasts (AML20-30, formerly MDS-RAEB-t) to be categorised and treated as either MDS or AML. In addition, an artificial distinction between AML20-30 and AML30+ was made by regulatory agencies by initially restricting approval of azacitidine to AML20-30. Thus, uncertainty prevails regarding the diagnosis, prognosis and optimal treatment timing and strategy for patients with AML20-30. Here, we aim to provide clarification for patients treated with azacitidine front-line.
  
  
  METHODS
  The Austrian Azacitidine Registry is a multicentre database (ClinicalTrials.gov: NCT01595295). For this analysis, we selected 339 patients treated with azacitidine front-line. According to the WHO classification 53, 96 and 190 patients had MDS-RAEB-I, MDS-RAEB-II and AML (AML20-30: n = 79; AML30+: n = 111), respectively. According to the FAB classification, 131, 101 and 111 patients had MDS-RAEB, MDS-RAEB-t and AML, respectively.
  
  
  RESULTS
  The median ages of patients with MDS and AML were 72 (range 37-87) and 77 (range 23-93) years, respectively. Overall, 80 % of classifiable patients (≤30 % bone marrow blasts) had intermediate-2 or high-risk IPSS scores. Most other baseline, treatment and response characteristics were similar between patients diagnosed with MDS or AML. WHO-classified patients with AML20-30 had significantly worse OS than patients with MDS-RAEB-II (13.1 vs 18.9 months; p = 0.010), but similar OS to patients with AML30+ (10.9 vs 13.1 months; p = 0.238). AML patients that showed MDS-related features did not have worse outcomes compared with patients who did not (13.2 vs 8.9 months; p = 0.104). FAB-classified patients with MDS-RAEB-t had similar survival to patients with AML30+ (12.8 vs 10.9 months; p = 0.376), but significantly worse OS than patients with MDS-RAEB (10.9 vs 24.4 months; p < 0.001).
  
  
  CONCLUSIONS
  Our data demonstrate the validity of the WHO classification of MDS and AML, and its superiority over the former FAB classification, for patients treated with azacitidine front-line. Neither bone marrow blast count nor presence of MDS-related features had an adverse prognostic impact on survival. Patients with AML20-30 should therefore be regarded as having 'true AML' and in our opinion treatment should be initiated without delay.
authors.affiliation: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria. l.pleyer@salk.at.|Center for Clinical Cancer and Immunology Trials at Salzburg Cancer Research Institute, Salzburg, Austria. l.pleyer@salk.at.|Cancer Cluster Salzburg, Salzburg, Austria. l.pleyer@salk.at.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pleyer
authors.affiliation: Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Burgstaller
authors.affiliation: Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Stauder
authors.affiliation: Department of Hematology and Oncology, Elisabethinen Hospital, Linz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Girschikofsky
authors.affiliation: Department of Hematology, Medical University of Graz, Graz, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Sill
authors.affiliation: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria.|Center for Clinical Cancer and Immunology Trials at Salzburg Cancer Research Institute, Salzburg, Austria.|Cancer Cluster Salzburg, Salzburg, Austria.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Schlick
authors.affiliation: Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Thaler
authors.affiliation: Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Britta
authors.initials: B
authors.lastname: Halter
authors.affiliation: Department of Hematology and Oncology, Elisabethinen Hospital, Linz, Austria.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Machherndl-Spandl
authors.affiliation: Department of Hematology, Medical University of Graz, Graz, Austria.
authors.forename: Armin
authors.initials: A
authors.lastname: Zebisch
authors.affiliation: Department for Hematology and Oncology, LKH Leoben, Leoben, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Pichler
authors.affiliation: 3rd Medical Department for Hematology and Oncology, Hanusch Hospital, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeilstöcker
authors.affiliation: First Medical Department, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna, Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Autzinger
authors.affiliation: Department of Internal Medicine, LKH Feldkirch, Feldkirch, Austria.
authors.forename: Alois
authors.initials: A
authors.lastname: Lang
authors.affiliation: 5th Medical Department, Hospital Hietzing, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Geissler
authors.affiliation: Department of Internal Medicine III, General Hospital, Linz, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Voskova
authors.affiliation: 1st Medical department, Klinikum Klagenfurt, Klagenfurt, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Geissler
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.affiliation: Department of Internal Medicine, LKH Fürstenfeld, Fürstenfeld, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hojas
authors.affiliation: Department of Hematology, Clinical Hospital Merkur, Zagreb, Croatia.
authors.forename: Inga M
authors.initials: IM
authors.lastname: Rogulj
authors.affiliation: Department of Internal Medicine II, LKH Steyr, Steyr, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Andel
authors.affiliation: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria.|Center for Clinical Cancer and Immunology Trials at Salzburg Cancer Research Institute, Salzburg, Austria.|Cancer Cluster Salzburg, Salzburg, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001317:Austria; D001374:Azacitidine / Q000627:therapeutic use*; D005260:Female; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries / Q000706:statistics & numerical data*; D006113:United Kingdom; D014481:United States; D014944:World Health Organization
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
keywords: AML; Austrian Azacitidine Registry; Azacitidine; Bone marrow blast count; Classification; FAB; MDS; RAEB-t; WHO