title: Azacitidine frontline therapy for unfit acute myeloid leukemia patients: clinical use and outcome prediction.
abstract: Hypomethylating agents are able to prolong the overall survival of some patients diagnosed with acute myeloid leukemia. The aim of this study was to evaluate the clinical use of azacitidine as front-line therapy in unfit acute myeloid leukemia (AML) patients and to develop a clinical prediction model to identify which patients may benefit more from the drug. One hundred and ten untreated unfit AML patients received front-line azacitidine therapy in Spain, and response and survival were evaluated in them following European LeukemiaNet (ELN) guidelines. A clinical prediction rule was obtained from this population that was validated and refined in 261 patients treated in France, Austria and Italy. ELN response was achieved in 21.0% of the 371 patients (CI95% 17.0-25.5) and did not depend on bone marrow blast cell percentage. Median overall survival was 9.6 months (CI95% 8.5-10.8) and 40.6% of the patients were alive at 1 year (CI95% 35.5-45.7). European ALMA score (E-ALMA), based on performance status, white blood cell counts at azacitidine onset and cytogenetics, discriminated three risk groups with different survival and response rates. Azacitidine seems a reasonable therapeutic option for most unfit AML patients, i.e. those displaying a favorable or intermediate E-ALMA score.
authors.affiliation: Department of Hematology, University Hospital, León, Spain; Institute of Biomedicine (IBIOMED), University of León, Spain. Electronic address: mail@fernandoramosmd.es.
authors.forename: F
authors.initials: F
authors.lastname: Ramos
authors.affiliation: Department of Blood Diseases/Hematology, CHU, Angers, France.
authors.forename: S
authors.initials: S
authors.lastname: Thépot
authors.affiliation: 3rd Med. Dept. with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center; Paracelsus Medical University Hospital Salzburg, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Pleyer
authors.affiliation: Department of Hematology, Tor Vergata Foundation Polyclinic, University of Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Maurillo
authors.affiliation: Department of Hematology, Saint Louis Hospital Paris VII University (APHP), France.
authors.forename: R
authors.initials: R
authors.lastname: Itzykson
authors.affiliation: Department of Hematology, Son Llatzer Hospital, Palma de Mallorca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bargay
authors.affiliation: Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Innsbruck, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Stauder
authors.affiliation: Department of Hematology, Tor Vergata Foundation Polyclinic, University of Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Venditti
authors.affiliation: Department of Hematology, Avicenne Hospital, Paris XIII University (APHP), Bobigny, France.
authors.forename: V
authors.initials: V
authors.lastname: Seegers
authors.affiliation: Department of Hematology, University Hospital, León, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Martínez-Robles
authors.affiliation: Department of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Burgstaller
authors.affiliation: Department of Hematology, CHU, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Récher
authors.affiliation: Department of Hematology, University Hospital, A Coruña, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Debén
authors.affiliation: Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Department of Hematology, Avicenne Hospital, Paris XIII University (APHP), Bobigny, France.
authors.forename: C
authors.initials: C
authors.lastname: Gardin
authors.affiliation: Scientific Direction, IRCCS; Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Musto
authors.affiliation: 3rd Med. Dept. with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center; Paracelsus Medical University Hospital Salzburg, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Greil
authors.affiliation: Department of Hematology, University Hospital, Salamanca, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Sánchez-Guijo
authors.affiliation: Department of Hematology, Saint Louis Hospital Paris VII University (APHP), France.
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D054928:Validation Studies as Topic
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
keywords: Acute myeloid leukemia; Azacitidine; Elderly; Prediction; Score; Unfit