Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group
Identifieur interne : 000415 ( Pmc/Checkpoint ); précédent : 000414; suivant : 000416Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group
Auteurs : Lisa Pleyer [Autriche] ; Hartmut Döhner ; Hervé Dombret ; John F. Seymour ; Andre C. Schuh ; Cl Beach ; Arlene S. Swern ; Sonja Burgstaller ; Reinhard Stauder ; Michael Girschikofsky ; Heinz Sill ; Konstantin Schlick ; Josef Thaler ; Britta Halter ; Sigrid Machherndl Spandl ; Armin Zebisch ; Angelika Pichler ; Michael Pfeilstöcker ; Eva M. Autzinger ; Alois Lang ; Klaus Geissler ; Daniela Voskova ; Wolfgang R. Sperr ; Sabine Hojas ; Inga M. Rogulj ; Johannes Andel ; Richard Greil [Autriche]Source :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2017.
Abstract
We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort;
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DOI: 10.3390/ijms18020415
PubMed: 28212292
PubMed Central: 5343949
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group</title><author><name sortKey="Pleyer, Lisa" sort="Pleyer, Lisa" uniqKey="Pleyer L" first="Lisa" last="Pleyer">Lisa Pleyer</name><affiliation><nlm:aff id="af1-ijms-18-00415">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 5020, Austria;<email>k.schlick@salk.at</email> (K.S.);<email>r.greil@mac.com</email> (R.G.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-18-00415">Cancer Cluster, Salzburg 5020, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Cancer Cluster, Salzburg 5020</wicri:regionArea><wicri:noRegion>Salzburg 5020</wicri:noRegion></affiliation></author><author><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><affiliation><nlm:aff id="af4-ijms-18-00415">Department of Medicine and Internal Medicine III, Universitätsklinikum Ulm, Ulm D-89081, Germany;<email>hartmut.doehner@uniklinik-ulm.de</email></nlm:aff></affiliation></author><author><name sortKey="Dombret, Herve" sort="Dombret, Herve" uniqKey="Dombret H" first="Hervé" last="Dombret">Hervé Dombret</name><affiliation><nlm:aff id="af5-ijms-18-00415">Institut Universitaire d’Hématologie, Hôpital Saint Louis, University Paris Diderot, Paris 75010, France;<email>herve.dombret@mac.com</email></nlm:aff></affiliation></author><author><name sortKey="Seymour, John F" sort="Seymour, John F" uniqKey="Seymour J" first="John F." last="Seymour">John F. Seymour</name><affiliation><nlm:aff id="af6-ijms-18-00415">Peter MacCallum Cancer Centre, East Melbourne, Australia, and University of Melbourne, Parkville 3000, Australia;<email>john.seymour@petermac.org</email></nlm:aff></affiliation></author><author><name sortKey="Schuh, Andre C" sort="Schuh, Andre C" uniqKey="Schuh A" first="Andre C." last="Schuh">Andre C. Schuh</name><affiliation><nlm:aff id="af7-ijms-18-00415">Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada;<email>andre.schuh@uhn.ca</email></nlm:aff></affiliation></author><author><name sortKey="Beach, Cl" sort="Beach, Cl" uniqKey="Beach C" first="Cl" last="Beach">Cl Beach</name><affiliation><nlm:aff id="af8-ijms-18-00415">Celgene Corporation, Summit, NJ 07901, USA;<email>clbeach@celgene.com</email> (C.L.B.),<email>aswern@celgene.com</email> (A.S.S.)</nlm:aff></affiliation></author><author><name sortKey="Swern, Arlene S" sort="Swern, Arlene S" uniqKey="Swern A" first="Arlene S." last="Swern">Arlene S. Swern</name><affiliation><nlm:aff id="af8-ijms-18-00415">Celgene Corporation, Summit, NJ 07901, USA;<email>clbeach@celgene.com</email> (C.L.B.),<email>aswern@celgene.com</email> (A.S.S.)</nlm:aff></affiliation></author><author><name sortKey="Burgstaller, Sonja" sort="Burgstaller, Sonja" uniqKey="Burgstaller S" first="Sonja" last="Burgstaller">Sonja Burgstaller</name><affiliation><nlm:aff id="af9-ijms-18-00415">Department of Internal Medicine IV, Klinikum WelsGrieskirchen, Wels 4600, Austria;<email>sonja.burgstaller@klinikum-wegr.at</email> (S.B.),<email>josef.thaler@klinikum-wegr.at</email> (J.T.)</nlm:aff></affiliation></author><author><name sortKey="Stauder, Reinhard" sort="Stauder, Reinhard" uniqKey="Stauder R" first="Reinhard" last="Stauder">Reinhard Stauder</name><affiliation><nlm:aff id="af10-ijms-18-00415">Department of Internal Medicine V, Innsbruck Medical University, Innsbruck 6020, Austria;<email>reinhard.stauder@i-med.ac.at</email> (R.S.),<email>britta.halter@i-med.ac.at</email> (B.H.)</nlm:aff></affiliation></author><author><name sortKey="Girschikofsky, Michael" sort="Girschikofsky, Michael" uniqKey="Girschikofsky M" first="Michael" last="Girschikofsky">Michael Girschikofsky</name><affiliation><nlm:aff id="af11-ijms-18-00415">Department of Hematology and Oncology, Elisabethinen Hospital, Linz 4020, Austria;<email>michael.girschikofsky@elisabethinen.or.at</email> (M.G.),<email>sigrid.machherndl-spandl@elisabethinen.or.at</email> (S.M.S.)</nlm:aff></affiliation></author><author><name sortKey="Sill, Heinz" sort="Sill, Heinz" uniqKey="Sill H" first="Heinz" last="Sill">Heinz Sill</name><affiliation><nlm:aff id="af12-ijms-18-00415">Department of Hematology, Medical University of Graz, Graz 8036, Austria;<email>heinz.sill@medunigraz.at</email> (H.S.),<email>armin.zebisch@medunigraz.at</email> (A.Z.)</nlm:aff></affiliation></author><author><name sortKey="Schlick, Konstantin" sort="Schlick, Konstantin" uniqKey="Schlick K" first="Konstantin" last="Schlick">Konstantin Schlick</name><affiliation><nlm:aff id="af1-ijms-18-00415">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 5020, Austria;<email>k.schlick@salk.at</email> (K.S.);<email>r.greil@mac.com</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Thaler, Josef" sort="Thaler, Josef" uniqKey="Thaler J" first="Josef" last="Thaler">Josef Thaler</name><affiliation><nlm:aff id="af9-ijms-18-00415">Department of Internal Medicine IV, Klinikum WelsGrieskirchen, Wels 4600, Austria;<email>sonja.burgstaller@klinikum-wegr.at</email> (S.B.),<email>josef.thaler@klinikum-wegr.at</email> (J.T.)</nlm:aff></affiliation></author><author><name sortKey="Halter, Britta" sort="Halter, Britta" uniqKey="Halter B" first="Britta" last="Halter">Britta Halter</name><affiliation><nlm:aff id="af10-ijms-18-00415">Department of Internal Medicine V, Innsbruck Medical University, Innsbruck 6020, Austria;<email>reinhard.stauder@i-med.ac.at</email> (R.S.),<email>britta.halter@i-med.ac.at</email> (B.H.)</nlm:aff></affiliation></author><author><name sortKey="Machherndl Spandl, Sigrid" sort="Machherndl Spandl, Sigrid" uniqKey="Machherndl Spandl S" first="Sigrid" last="Machherndl Spandl">Sigrid Machherndl Spandl</name><affiliation><nlm:aff id="af11-ijms-18-00415">Department of Hematology and Oncology, Elisabethinen Hospital, Linz 4020, Austria;<email>michael.girschikofsky@elisabethinen.or.at</email> (M.G.),<email>sigrid.machherndl-spandl@elisabethinen.or.at</email> (S.M.S.)</nlm:aff></affiliation></author><author><name sortKey="Zebisch, Armin" sort="Zebisch, Armin" uniqKey="Zebisch A" first="Armin" last="Zebisch">Armin Zebisch</name><affiliation><nlm:aff id="af12-ijms-18-00415">Department of Hematology, Medical University of Graz, Graz 8036, Austria;<email>heinz.sill@medunigraz.at</email> (H.S.),<email>armin.zebisch@medunigraz.at</email> (A.Z.)</nlm:aff></affiliation></author><author><name sortKey="Pichler, Angelika" sort="Pichler, Angelika" uniqKey="Pichler A" first="Angelika" last="Pichler">Angelika Pichler</name><affiliation><nlm:aff id="af13-ijms-18-00415">Department for Hematology and Oncology, LKH Leoben, Leoben 8700, Austria;<email>angelika.pichler@kages.at</email></nlm:aff></affiliation></author><author><name sortKey="Pfeilstocker, Michael" sort="Pfeilstocker, Michael" uniqKey="Pfeilstocker M" first="Michael" last="Pfeilstöcker">Michael Pfeilstöcker</name><affiliation><nlm:aff id="af14-ijms-18-00415">3rd Medical Department for Hematology and Oncology, Hanusch Hospital, Vienna 1140, Austria;<email>m.pfeilstoecker@aon.at</email></nlm:aff></affiliation></author><author><name sortKey="Autzinger, Eva M" sort="Autzinger, Eva M" uniqKey="Autzinger E" first="Eva M." last="Autzinger">Eva M. Autzinger</name><affiliation><nlm:aff id="af15-ijms-18-00415">First Medical Department, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna 1160, Austria;<email>eva-maria.autzinger@wienkav.at</email></nlm:aff></affiliation></author><author><name sortKey="Lang, Alois" sort="Lang, Alois" uniqKey="Lang A" first="Alois" last="Lang">Alois Lang</name><affiliation><nlm:aff id="af16-ijms-18-00415">Department of Internal Medicine, Landeskrankenhaus Feldkirch (LKH) Feldkirch, Feldkirch 6800, Austria;<email>alois.lang@lkhf.at</email></nlm:aff></affiliation></author><author><name sortKey="Geissler, Klaus" sort="Geissler, Klaus" uniqKey="Geissler K" first="Klaus" last="Geissler">Klaus Geissler</name><affiliation><nlm:aff id="af17-ijms-18-00415">5th Medical Department, Hospital Hietzing, Vienna 1130, Austria;<email>klaus.geissler@wienkav.at</email></nlm:aff></affiliation></author><author><name sortKey="Voskova, Daniela" sort="Voskova, Daniela" uniqKey="Voskova D" first="Daniela" last="Voskova">Daniela Voskova</name><affiliation><nlm:aff id="af18-ijms-18-00415">Department of Internal Medicine III, General Hospital, Linz 4020, Austria;<email>daniela.voskova@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Sperr, Wolfgang R" sort="Sperr, Wolfgang R" uniqKey="Sperr W" first="Wolfgang R." last="Sperr">Wolfgang R. Sperr</name><affiliation><nlm:aff id="af19-ijms-18-00415">Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna 1090, Austria;<email>wolfgang.r.sperr@meduniwien.ac.at</email></nlm:aff></affiliation></author><author><name sortKey="Hojas, Sabine" sort="Hojas, Sabine" uniqKey="Hojas S" first="Sabine" last="Hojas">Sabine Hojas</name><affiliation><nlm:aff id="af20-ijms-18-00415">Department of Internal Medicine, LKH Fürstenfeld, Fürstenfeld 8280, Austria;<email>sabineelisabeth.hojas@kages.at</email></nlm:aff></affiliation></author><author><name sortKey="Rogulj, Inga M" sort="Rogulj, Inga M" uniqKey="Rogulj I" first="Inga M." last="Rogulj">Inga M. Rogulj</name><affiliation><nlm:aff id="af21-ijms-18-00415">Department of Hematology, Clinical Hospital Merkur, Zagreb 10000, Croatia;<email>imandac@yahoo.com</email></nlm:aff></affiliation></author><author><name sortKey="Andel, Johannes" sort="Andel, Johannes" uniqKey="Andel J" first="Johannes" last="Andel">Johannes Andel</name><affiliation><nlm:aff id="af22-ijms-18-00415">Department of Internal Medicine II, LKH Steyr, Steyr 4400, Austria;<email>johannes.andel@gespag.at</email></nlm:aff></affiliation></author><author><name sortKey="Greil, Richard" sort="Greil, Richard" uniqKey="Greil R" first="Richard" last="Greil">Richard Greil</name><affiliation><nlm:aff id="af1-ijms-18-00415">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 5020, Austria;<email>k.schlick@salk.at</email> (K.S.);<email>r.greil@mac.com</email> (R.G.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-18-00415">Salzburg Cancer Research Institute—Center for Clinical Cancer and Immunology Trials, Salzburg 5020, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Salzburg Cancer Research Institute—Center for Clinical Cancer and Immunology Trials, Salzburg 5020</wicri:regionArea><wicri:noRegion>Salzburg 5020</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-18-00415">Cancer Cluster, Salzburg 5020, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Cancer Cluster, Salzburg 5020</wicri:regionArea><wicri:noRegion>Salzburg 5020</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28212292</idno><idno type="pmc">5343949</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343949</idno><idno type="RBID">PMC:5343949</idno><idno type="doi">10.3390/ijms18020415</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">002603</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002603</idno><idno type="wicri:Area/Pmc/Curation">002453</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002453</idno><idno type="wicri:Area/Pmc/Checkpoint">000415</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000415</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group</title><author><name sortKey="Pleyer, Lisa" sort="Pleyer, Lisa" uniqKey="Pleyer L" first="Lisa" last="Pleyer">Lisa Pleyer</name><affiliation><nlm:aff id="af1-ijms-18-00415">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 5020, Austria;<email>k.schlick@salk.at</email> (K.S.);<email>r.greil@mac.com</email> (R.G.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-18-00415">Cancer Cluster, Salzburg 5020, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Cancer Cluster, Salzburg 5020</wicri:regionArea><wicri:noRegion>Salzburg 5020</wicri:noRegion></affiliation></author><author><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><affiliation><nlm:aff id="af4-ijms-18-00415">Department of Medicine and Internal Medicine III, Universitätsklinikum Ulm, Ulm D-89081, Germany;<email>hartmut.doehner@uniklinik-ulm.de</email></nlm:aff></affiliation></author><author><name sortKey="Dombret, Herve" sort="Dombret, Herve" uniqKey="Dombret H" first="Hervé" last="Dombret">Hervé Dombret</name><affiliation><nlm:aff id="af5-ijms-18-00415">Institut Universitaire d’Hématologie, Hôpital Saint Louis, University Paris Diderot, Paris 75010, France;<email>herve.dombret@mac.com</email></nlm:aff></affiliation></author><author><name sortKey="Seymour, John F" sort="Seymour, John F" uniqKey="Seymour J" first="John F." last="Seymour">John F. Seymour</name><affiliation><nlm:aff id="af6-ijms-18-00415">Peter MacCallum Cancer Centre, East Melbourne, Australia, and University of Melbourne, Parkville 3000, Australia;<email>john.seymour@petermac.org</email></nlm:aff></affiliation></author><author><name sortKey="Schuh, Andre C" sort="Schuh, Andre C" uniqKey="Schuh A" first="Andre C." last="Schuh">Andre C. Schuh</name><affiliation><nlm:aff id="af7-ijms-18-00415">Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada;<email>andre.schuh@uhn.ca</email></nlm:aff></affiliation></author><author><name sortKey="Beach, Cl" sort="Beach, Cl" uniqKey="Beach C" first="Cl" last="Beach">Cl Beach</name><affiliation><nlm:aff id="af8-ijms-18-00415">Celgene Corporation, Summit, NJ 07901, USA;<email>clbeach@celgene.com</email> (C.L.B.),<email>aswern@celgene.com</email> (A.S.S.)</nlm:aff></affiliation></author><author><name sortKey="Swern, Arlene S" sort="Swern, Arlene S" uniqKey="Swern A" first="Arlene S." last="Swern">Arlene S. Swern</name><affiliation><nlm:aff id="af8-ijms-18-00415">Celgene Corporation, Summit, NJ 07901, USA;<email>clbeach@celgene.com</email> (C.L.B.),<email>aswern@celgene.com</email> (A.S.S.)</nlm:aff></affiliation></author><author><name sortKey="Burgstaller, Sonja" sort="Burgstaller, Sonja" uniqKey="Burgstaller S" first="Sonja" last="Burgstaller">Sonja Burgstaller</name><affiliation><nlm:aff id="af9-ijms-18-00415">Department of Internal Medicine IV, Klinikum WelsGrieskirchen, Wels 4600, Austria;<email>sonja.burgstaller@klinikum-wegr.at</email> (S.B.),<email>josef.thaler@klinikum-wegr.at</email> (J.T.)</nlm:aff></affiliation></author><author><name sortKey="Stauder, Reinhard" sort="Stauder, Reinhard" uniqKey="Stauder R" first="Reinhard" last="Stauder">Reinhard Stauder</name><affiliation><nlm:aff id="af10-ijms-18-00415">Department of Internal Medicine V, Innsbruck Medical University, Innsbruck 6020, Austria;<email>reinhard.stauder@i-med.ac.at</email> (R.S.),<email>britta.halter@i-med.ac.at</email> (B.H.)</nlm:aff></affiliation></author><author><name sortKey="Girschikofsky, Michael" sort="Girschikofsky, Michael" uniqKey="Girschikofsky M" first="Michael" last="Girschikofsky">Michael Girschikofsky</name><affiliation><nlm:aff id="af11-ijms-18-00415">Department of Hematology and Oncology, Elisabethinen Hospital, Linz 4020, Austria;<email>michael.girschikofsky@elisabethinen.or.at</email> (M.G.),<email>sigrid.machherndl-spandl@elisabethinen.or.at</email> (S.M.S.)</nlm:aff></affiliation></author><author><name sortKey="Sill, Heinz" sort="Sill, Heinz" uniqKey="Sill H" first="Heinz" last="Sill">Heinz Sill</name><affiliation><nlm:aff id="af12-ijms-18-00415">Department of Hematology, Medical University of Graz, Graz 8036, Austria;<email>heinz.sill@medunigraz.at</email> (H.S.),<email>armin.zebisch@medunigraz.at</email> (A.Z.)</nlm:aff></affiliation></author><author><name sortKey="Schlick, Konstantin" sort="Schlick, Konstantin" uniqKey="Schlick K" first="Konstantin" last="Schlick">Konstantin Schlick</name><affiliation><nlm:aff id="af1-ijms-18-00415">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 5020, Austria;<email>k.schlick@salk.at</email> (K.S.);<email>r.greil@mac.com</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Thaler, Josef" sort="Thaler, Josef" uniqKey="Thaler J" first="Josef" last="Thaler">Josef Thaler</name><affiliation><nlm:aff id="af9-ijms-18-00415">Department of Internal Medicine IV, Klinikum WelsGrieskirchen, Wels 4600, Austria;<email>sonja.burgstaller@klinikum-wegr.at</email> (S.B.),<email>josef.thaler@klinikum-wegr.at</email> (J.T.)</nlm:aff></affiliation></author><author><name sortKey="Halter, Britta" sort="Halter, Britta" uniqKey="Halter B" first="Britta" last="Halter">Britta Halter</name><affiliation><nlm:aff id="af10-ijms-18-00415">Department of Internal Medicine V, Innsbruck Medical University, Innsbruck 6020, Austria;<email>reinhard.stauder@i-med.ac.at</email> (R.S.),<email>britta.halter@i-med.ac.at</email> (B.H.)</nlm:aff></affiliation></author><author><name sortKey="Machherndl Spandl, Sigrid" sort="Machherndl Spandl, Sigrid" uniqKey="Machherndl Spandl S" first="Sigrid" last="Machherndl Spandl">Sigrid Machherndl Spandl</name><affiliation><nlm:aff id="af11-ijms-18-00415">Department of Hematology and Oncology, Elisabethinen Hospital, Linz 4020, Austria;<email>michael.girschikofsky@elisabethinen.or.at</email> (M.G.),<email>sigrid.machherndl-spandl@elisabethinen.or.at</email> (S.M.S.)</nlm:aff></affiliation></author><author><name sortKey="Zebisch, Armin" sort="Zebisch, Armin" uniqKey="Zebisch A" first="Armin" last="Zebisch">Armin Zebisch</name><affiliation><nlm:aff id="af12-ijms-18-00415">Department of Hematology, Medical University of Graz, Graz 8036, Austria;<email>heinz.sill@medunigraz.at</email> (H.S.),<email>armin.zebisch@medunigraz.at</email> (A.Z.)</nlm:aff></affiliation></author><author><name sortKey="Pichler, Angelika" sort="Pichler, Angelika" uniqKey="Pichler A" first="Angelika" last="Pichler">Angelika Pichler</name><affiliation><nlm:aff id="af13-ijms-18-00415">Department for Hematology and Oncology, LKH Leoben, Leoben 8700, Austria;<email>angelika.pichler@kages.at</email></nlm:aff></affiliation></author><author><name sortKey="Pfeilstocker, Michael" sort="Pfeilstocker, Michael" uniqKey="Pfeilstocker M" first="Michael" last="Pfeilstöcker">Michael Pfeilstöcker</name><affiliation><nlm:aff id="af14-ijms-18-00415">3rd Medical Department for Hematology and Oncology, Hanusch Hospital, Vienna 1140, Austria;<email>m.pfeilstoecker@aon.at</email></nlm:aff></affiliation></author><author><name sortKey="Autzinger, Eva M" sort="Autzinger, Eva M" uniqKey="Autzinger E" first="Eva M." last="Autzinger">Eva M. Autzinger</name><affiliation><nlm:aff id="af15-ijms-18-00415">First Medical Department, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna 1160, Austria;<email>eva-maria.autzinger@wienkav.at</email></nlm:aff></affiliation></author><author><name sortKey="Lang, Alois" sort="Lang, Alois" uniqKey="Lang A" first="Alois" last="Lang">Alois Lang</name><affiliation><nlm:aff id="af16-ijms-18-00415">Department of Internal Medicine, Landeskrankenhaus Feldkirch (LKH) Feldkirch, Feldkirch 6800, Austria;<email>alois.lang@lkhf.at</email></nlm:aff></affiliation></author><author><name sortKey="Geissler, Klaus" sort="Geissler, Klaus" uniqKey="Geissler K" first="Klaus" last="Geissler">Klaus Geissler</name><affiliation><nlm:aff id="af17-ijms-18-00415">5th Medical Department, Hospital Hietzing, Vienna 1130, Austria;<email>klaus.geissler@wienkav.at</email></nlm:aff></affiliation></author><author><name sortKey="Voskova, Daniela" sort="Voskova, Daniela" uniqKey="Voskova D" first="Daniela" last="Voskova">Daniela Voskova</name><affiliation><nlm:aff id="af18-ijms-18-00415">Department of Internal Medicine III, General Hospital, Linz 4020, Austria;<email>daniela.voskova@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Sperr, Wolfgang R" sort="Sperr, Wolfgang R" uniqKey="Sperr W" first="Wolfgang R." last="Sperr">Wolfgang R. Sperr</name><affiliation><nlm:aff id="af19-ijms-18-00415">Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna 1090, Austria;<email>wolfgang.r.sperr@meduniwien.ac.at</email></nlm:aff></affiliation></author><author><name sortKey="Hojas, Sabine" sort="Hojas, Sabine" uniqKey="Hojas S" first="Sabine" last="Hojas">Sabine Hojas</name><affiliation><nlm:aff id="af20-ijms-18-00415">Department of Internal Medicine, LKH Fürstenfeld, Fürstenfeld 8280, Austria;<email>sabineelisabeth.hojas@kages.at</email></nlm:aff></affiliation></author><author><name sortKey="Rogulj, Inga M" sort="Rogulj, Inga M" uniqKey="Rogulj I" first="Inga M." last="Rogulj">Inga M. Rogulj</name><affiliation><nlm:aff id="af21-ijms-18-00415">Department of Hematology, Clinical Hospital Merkur, Zagreb 10000, Croatia;<email>imandac@yahoo.com</email></nlm:aff></affiliation></author><author><name sortKey="Andel, Johannes" sort="Andel, Johannes" uniqKey="Andel J" first="Johannes" last="Andel">Johannes Andel</name><affiliation><nlm:aff id="af22-ijms-18-00415">Department of Internal Medicine II, LKH Steyr, Steyr 4400, Austria;<email>johannes.andel@gespag.at</email></nlm:aff></affiliation></author><author><name sortKey="Greil, Richard" sort="Greil, Richard" uniqKey="Greil R" first="Richard" last="Greil">Richard Greil</name><affiliation><nlm:aff id="af1-ijms-18-00415">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 5020, Austria;<email>k.schlick@salk.at</email> (K.S.);<email>r.greil@mac.com</email> (R.G.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-18-00415">Salzburg Cancer Research Institute—Center for Clinical Cancer and Immunology Trials, Salzburg 5020, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Salzburg Cancer Research Institute—Center for Clinical Cancer and Immunology Trials, Salzburg 5020</wicri:regionArea><wicri:noRegion>Salzburg 5020</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-18-00415">Cancer Cluster, Salzburg 5020, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Cancer Cluster, Salzburg 5020</wicri:regionArea><wicri:noRegion>Salzburg 5020</wicri:noRegion></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; <italic>n</italic> = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; <italic>n</italic> = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (<italic>p</italic> = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (<italic>n</italic> = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (<italic>n</italic> = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO-AML)” cohort; <italic>n</italic> = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (<italic>p</italic> = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Klepin, H D" uniqKey="Klepin H">H.D. Klepin</name></author><author><name sortKey="Balducci, L" uniqKey="Balducci L">L. Balducci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Appelbaum, F R" uniqKey="Appelbaum F">F.R. Appelbaum</name></author><author><name sortKey="Gundacker, H" uniqKey="Gundacker H">H. Gundacker</name></author><author><name sortKey="Head, D R" uniqKey="Head D">D.R. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Mol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id><journal-id journal-id-type="publisher-id">ijms</journal-id><journal-title-group><journal-title>International Journal of Molecular Sciences</journal-title></journal-title-group><issn pub-type="epub">1422-0067</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28212292</article-id><article-id pub-id-type="pmc">5343949</article-id><article-id pub-id-type="doi">10.3390/ijms18020415</article-id><article-id pub-id-type="publisher-id">ijms-18-00415</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Pleyer</surname><given-names>Lisa</given-names></name><xref ref-type="aff" rid="af1-ijms-18-00415">1</xref><xref ref-type="aff" rid="af3-ijms-18-00415">3</xref><xref rid="c1-ijms-18-00415" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Döhner</surname><given-names>Hartmut</given-names></name><xref ref-type="aff" rid="af4-ijms-18-00415">4</xref></contrib><contrib contrib-type="author"><name><surname>Dombret</surname><given-names>Hervé</given-names></name><xref ref-type="aff" rid="af5-ijms-18-00415">5</xref></contrib><contrib contrib-type="author"><name><surname>Seymour</surname><given-names>John F.</given-names></name><xref ref-type="aff" rid="af6-ijms-18-00415">6</xref></contrib><contrib contrib-type="author"><name><surname>Schuh</surname><given-names>Andre C.</given-names></name><xref ref-type="aff" rid="af7-ijms-18-00415">7</xref></contrib><contrib contrib-type="author"><name><surname>Beach</surname><given-names>CL</given-names></name><xref ref-type="aff" rid="af8-ijms-18-00415">8</xref></contrib><contrib contrib-type="author"><name><surname>Swern</surname><given-names>Arlene S.</given-names></name><xref ref-type="aff" rid="af8-ijms-18-00415">8</xref></contrib><contrib contrib-type="author"><name><surname>Burgstaller</surname><given-names>Sonja</given-names></name><xref ref-type="aff" rid="af9-ijms-18-00415">9</xref></contrib><contrib contrib-type="author"><name><surname>Stauder</surname><given-names>Reinhard</given-names></name><xref ref-type="aff" rid="af10-ijms-18-00415">10</xref></contrib><contrib contrib-type="author"><name><surname>Girschikofsky</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="af11-ijms-18-00415">11</xref></contrib><contrib contrib-type="author"><name><surname>Sill</surname><given-names>Heinz</given-names></name><xref ref-type="aff" rid="af12-ijms-18-00415">12</xref></contrib><contrib contrib-type="author"><name><surname>Schlick</surname><given-names>Konstantin</given-names></name><xref ref-type="aff" rid="af1-ijms-18-00415">1</xref></contrib><contrib contrib-type="author"><name><surname>Thaler</surname><given-names>Josef</given-names></name><xref ref-type="aff" rid="af9-ijms-18-00415">9</xref></contrib><contrib contrib-type="author"><name><surname>Halter</surname><given-names>Britta</given-names></name><xref ref-type="aff" rid="af10-ijms-18-00415">10</xref></contrib><contrib contrib-type="author"><name><surname>Machherndl Spandl</surname><given-names>Sigrid</given-names></name><xref ref-type="aff" rid="af11-ijms-18-00415">11</xref></contrib><contrib contrib-type="author"><name><surname>Zebisch</surname><given-names>Armin</given-names></name><xref ref-type="aff" rid="af12-ijms-18-00415">12</xref></contrib><contrib contrib-type="author"><name><surname>Pichler</surname><given-names>Angelika</given-names></name><xref ref-type="aff" rid="af13-ijms-18-00415">13</xref></contrib><contrib contrib-type="author"><name><surname>Pfeilstöcker</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="af14-ijms-18-00415">14</xref></contrib><contrib contrib-type="author"><name><surname>Autzinger</surname><given-names>Eva M.</given-names></name><xref ref-type="aff" rid="af15-ijms-18-00415">15</xref></contrib><contrib contrib-type="author"><name><surname>Lang</surname><given-names>Alois</given-names></name><xref ref-type="aff" rid="af16-ijms-18-00415">16</xref></contrib><contrib contrib-type="author"><name><surname>Geissler</surname><given-names>Klaus</given-names></name><xref ref-type="aff" rid="af17-ijms-18-00415">17</xref></contrib><contrib contrib-type="author"><name><surname>Voskova</surname><given-names>Daniela</given-names></name><xref ref-type="aff" rid="af18-ijms-18-00415">18</xref></contrib><contrib contrib-type="author"><name><surname>Sperr</surname><given-names>Wolfgang R.</given-names></name><xref ref-type="aff" rid="af19-ijms-18-00415">19</xref></contrib><contrib contrib-type="author"><name><surname>Hojas</surname><given-names>Sabine</given-names></name><xref ref-type="aff" rid="af20-ijms-18-00415">20</xref></contrib><contrib contrib-type="author"><name><surname>Rogulj</surname><given-names>Inga M.</given-names></name><xref ref-type="aff" rid="af21-ijms-18-00415">21</xref></contrib><contrib contrib-type="author"><name><surname>Andel</surname><given-names>Johannes</given-names></name><xref ref-type="aff" rid="af22-ijms-18-00415">22</xref></contrib><contrib contrib-type="author"><name><surname>Greil</surname><given-names>Richard</given-names></name><xref ref-type="aff" rid="af1-ijms-18-00415">1</xref><xref ref-type="aff" rid="af2-ijms-18-00415">2</xref><xref ref-type="aff" rid="af3-ijms-18-00415">3</xref></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Brown</surname><given-names>Geoffrey</given-names></name><role>Academic Editor</role></contrib><contrib contrib-type="editor"><name><surname>Marcinkowska</surname><given-names>Ewa</given-names></name><role>Academic Editor</role></contrib></contrib-group><aff id="af1-ijms-18-00415"><label>1</label>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 5020, Austria;<email>k.schlick@salk.at</email> (K.S.);<email>r.greil@mac.com</email> (R.G.)</aff><aff id="af2-ijms-18-00415"><label>2</label>Salzburg Cancer Research Institute—Center for Clinical Cancer and Immunology Trials, Salzburg 5020, Austria</aff><aff id="af3-ijms-18-00415"><label>3</label>Cancer Cluster, Salzburg 5020, Austria</aff><aff id="af4-ijms-18-00415"><label>4</label>Department of Medicine and Internal Medicine III, Universitätsklinikum Ulm, Ulm D-89081, Germany;<email>hartmut.doehner@uniklinik-ulm.de</email></aff><aff id="af5-ijms-18-00415"><label>5</label>Institut Universitaire d’Hématologie, Hôpital Saint Louis, University Paris Diderot, Paris 75010, France;<email>herve.dombret@mac.com</email></aff><aff id="af6-ijms-18-00415"><label>6</label>Peter MacCallum Cancer Centre, East Melbourne, Australia, and University of Melbourne, Parkville 3000, Australia;<email>john.seymour@petermac.org</email></aff><aff id="af7-ijms-18-00415"><label>7</label>Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada;<email>andre.schuh@uhn.ca</email></aff><aff id="af8-ijms-18-00415"><label>8</label>Celgene Corporation, Summit, NJ 07901, USA;<email>clbeach@celgene.com</email> (C.L.B.),<email>aswern@celgene.com</email> (A.S.S.)</aff><aff id="af9-ijms-18-00415"><label>9</label>Department of Internal Medicine IV, Klinikum WelsGrieskirchen, Wels 4600, Austria;<email>sonja.burgstaller@klinikum-wegr.at</email> (S.B.),<email>josef.thaler@klinikum-wegr.at</email> (J.T.)</aff><aff id="af10-ijms-18-00415"><label>10</label>Department of Internal Medicine V, Innsbruck Medical University, Innsbruck 6020, Austria;<email>reinhard.stauder@i-med.ac.at</email> (R.S.),<email>britta.halter@i-med.ac.at</email> (B.H.)</aff><aff id="af11-ijms-18-00415"><label>11</label>Department of Hematology and Oncology, Elisabethinen Hospital, Linz 4020, Austria;<email>michael.girschikofsky@elisabethinen.or.at</email> (M.G.),<email>sigrid.machherndl-spandl@elisabethinen.or.at</email> (S.M.S.)</aff><aff id="af12-ijms-18-00415"><label>12</label>Department of Hematology, Medical University of Graz, Graz 8036, Austria;<email>heinz.sill@medunigraz.at</email> (H.S.),<email>armin.zebisch@medunigraz.at</email> (A.Z.)</aff><aff id="af13-ijms-18-00415"><label>13</label>Department for Hematology and Oncology, LKH Leoben, Leoben 8700, Austria;<email>angelika.pichler@kages.at</email></aff><aff id="af14-ijms-18-00415"><label>14</label>3rd Medical Department for Hematology and Oncology, Hanusch Hospital, Vienna 1140, Austria;<email>m.pfeilstoecker@aon.at</email></aff><aff id="af15-ijms-18-00415"><label>15</label>First Medical Department, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna 1160, Austria;<email>eva-maria.autzinger@wienkav.at</email></aff><aff id="af16-ijms-18-00415"><label>16</label>Department of Internal Medicine, Landeskrankenhaus Feldkirch (LKH) Feldkirch, Feldkirch 6800, Austria;<email>alois.lang@lkhf.at</email></aff><aff id="af17-ijms-18-00415"><label>17</label>5th Medical Department, Hospital Hietzing, Vienna 1130, Austria;<email>klaus.geissler@wienkav.at</email></aff><aff id="af18-ijms-18-00415"><label>18</label>Department of Internal Medicine III, General Hospital, Linz 4020, Austria;<email>daniela.voskova@gmail.com</email></aff><aff id="af19-ijms-18-00415"><label>19</label>Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna 1090, Austria;<email>wolfgang.r.sperr@meduniwien.ac.at</email></aff><aff id="af20-ijms-18-00415"><label>20</label>Department of Internal Medicine, LKH Fürstenfeld, Fürstenfeld 8280, Austria;<email>sabineelisabeth.hojas@kages.at</email></aff><aff id="af21-ijms-18-00415"><label>21</label>Department of Hematology, Clinical Hospital Merkur, Zagreb 10000, Croatia;<email>imandac@yahoo.com</email></aff><aff id="af22-ijms-18-00415"><label>22</label>Department of Internal Medicine II, LKH Steyr, Steyr 4400, Austria;<email>johannes.andel@gespag.at</email></aff><author-notes><corresp id="c1-ijms-18-00415"><label>*</label>Correspondence: <email>l.pleyer@salk.at</email>; Tel.: +43-57255-58271</corresp></author-notes><pub-date pub-type="epub"><day>15</day><month>2</month><year>2017</year></pub-date><pub-date pub-type="collection"><month>2</month><year>2017</year></pub-date><volume>18</volume><issue>2</issue><elocation-id>415</elocation-id><history><date date-type="received"><day>08</day><month>12</month><year>2016</year></date><date date-type="accepted"><day>08</day><month>2</month><year>2017</year></date></history><permissions><copyright-statement>© 2017 by the authors.</copyright-statement><copyright-year>2017</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; <italic>n</italic> = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; <italic>n</italic> = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (<italic>p</italic> = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (<italic>n</italic> = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (<italic>n</italic> = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO-AML)” cohort; <italic>n</italic> = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (<italic>p</italic> = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML.</p></abstract><kwd-group><kwd>acute myeloid leukaemia (AML)</kwd><kwd>AZA-AML-001 trial</kwd><kwd>Austrian Azacitidine Registry (AAR)</kwd><kwd>real-world data</kwd><kwd>azacitidine</kwd></kwd-group></article-meta></front><floats-group><fig id="ijms-18-00415-f001" position="float"><label>Figure 1</label><caption><p>CONSORT diagram. <sup>a</sup> Subset of patients included in pooled analysis (AML-001-like).</p></caption><graphic xlink:href="ijms-18-00415-g001"></graphic></fig><fig id="ijms-18-00415-f002" position="float"><label>Figure 2</label><caption><p>Overall survival (OS) in AML patients with >30% BM blasts and <15 G/L WBC treated with azacitidine front-line within the AML-001 trial and the AAR-AML-001-like cohorts. (<bold>A</bold>) Total patient cohorts; (<bold>B</bold>) AML-MRC; (<bold>C</bold>) AML with NCCN poor-risk cytogenetics; (<bold>D</bold>) AML with NCCN intermediate-risk cytogenetics; and (<bold>E</bold>) Normal karyotype.</p></caption><graphic xlink:href="ijms-18-00415-g002"></graphic></fig><fig id="ijms-18-00415-f003" position="float"><label>Figure 3</label><caption><p>Median OS and one-year survival rates in AML patients with >30% BM blasts and <15 G/L WBC and WHO-AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry. (<bold>A</bold>) Total patient cohorts; (<bold>B</bold>) AML-MRC; (<bold>C</bold>) AML with NCCN poor-risk cytogenetics; (<bold>D</bold>) AML with NCCN intermediate-risk cytogenetics; and (<bold>E</bold>) Normal karyotype.</p></caption><graphic xlink:href="ijms-18-00415-g003"></graphic></fig><table-wrap id="ijms-18-00415-t001" position="float"><object-id pub-id-type="pii">ijms-18-00415-t001_Table 1</object-id><label>Table 1</label><caption><p>Baseline characteristics of acute myeloid leukaemia (AML) patients treated with azacitidine front-line per patient subset.</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="3" align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">Baseline Characteristics</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AML-001 Trial</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AAR (001-Like)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AAR (WHO-AML)</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Subset</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Subset</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Subset</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(<italic>n</italic> = 214)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(<italic>n</italic> = 95)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(<italic>n</italic> = 193)</th></tr></thead><tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Age, median (mean) [SD], years</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">76 (75.5) [5.6]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">77 (75.2) [11.5]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">77 (75.6) [10.2]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Age ≥75 years, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">58.4</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">56.8</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">58.5</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Male, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">57.5</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">54.7</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">58.6</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">ECOG-PS, %</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> 0–1</td><td align="center" valign="middle" rowspan="1" colspan="1">76.6</td><td align="center" valign="middle" rowspan="1" colspan="1">67.3</td><td align="center" valign="middle" rowspan="1" colspan="1">67.9</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> 2</td><td align="center" valign="middle" rowspan="1" colspan="1">23.4</td><td align="center" valign="middle" rowspan="1" colspan="1">23.2</td><td align="center" valign="middle" rowspan="1" colspan="1">24.4</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> 3–4 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.5</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.6</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">AML classification, %</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> AML-MRC <sup>b</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">57.0</td><td align="center" valign="middle" rowspan="1" colspan="1">66.3</td><td align="center" valign="middle" rowspan="1" colspan="1">70.8</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> AML-NOS</td><td align="center" valign="middle" rowspan="1" colspan="1">37.3</td><td align="center" valign="middle" rowspan="1" colspan="1">24.2</td><td align="center" valign="middle" rowspan="1" colspan="1">18.8</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> AML-RCA</td><td align="center" valign="middle" rowspan="1" colspan="1">2.3</td><td align="center" valign="middle" rowspan="1" colspan="1">4.2</td><td align="center" valign="middle" rowspan="1" colspan="1">3.7</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> t-AML</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.3</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5.3</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.8</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Antecedent haematological disease, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">19.6</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">25.3</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">31.6</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prior MDS, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">19.6</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">21.1</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">24.9</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">NCCN cytogenetic risk, %</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> Good <sup>c</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0</td><td align="center" valign="middle" rowspan="1" colspan="1">2.1</td><td align="center" valign="middle" rowspan="1" colspan="1">2.4</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> Intermediate</td><td align="center" valign="middle" rowspan="1" colspan="1">65.0</td><td align="center" valign="middle" rowspan="1" colspan="1">58.9</td><td align="center" valign="middle" rowspan="1" colspan="1">66.9</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> Normal</td><td align="center" valign="middle" rowspan="1" colspan="1">47.7</td><td align="center" valign="middle" rowspan="1" colspan="1">42.1</td><td align="center" valign="middle" rowspan="1" colspan="1">47.3</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Poor</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">34.6</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">27.4</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">30.8</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">BM blasts, median (range), %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">73.0 (31–100)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">55.5 (31–96)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">40.0 (20–100)</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">BM blasts ≥50%, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">78.0</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">58.9</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">38.9</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Number of cytopenias, %</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> 0–1</td><td align="center" valign="middle" rowspan="1" colspan="1">13.1</td><td align="center" valign="middle" rowspan="1" colspan="1">14.7</td><td align="center" valign="middle" rowspan="1" colspan="1">16.6</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> 2–3</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">86.9</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">85.3</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">83.4</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RBC-TD, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">70.1</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">60.0</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">52.9</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PLT-TD, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">40.2</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">30.5</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">24.9</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WBC, median (range), G/L</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.0 (0.3–14.7)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.1 (0.6–14.4)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.5 (0.6–74.1)</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hb, median (range), g/dL</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.5 (5.0–13.4)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.1 (5.8–13.6)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.1 (5.8–14.2)</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ANC, median (range), G/L</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.3 (0–5.3)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.5 (0–7.7)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.6 (0–37.2)</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PLT, median (range), G/L</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">54.0 (3–585)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">49.0 (7–1.270)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">52.0 (6–1,270)</td></tr></tbody></table><table-wrap-foot><fn><p><sup>a</sup> ECOG-PS > 2 was an exclusion criterion in the AZA-AML-001 trial. Nine patients included within the AAR had an ECOG-PS > 2; <sup>b</sup> The definition of MRC in the AZA-AML-001 trial was based on the presence of NCCN poor-risk cytogenetics. This means that the following cytogenetic aberrations (included in the WHO definition of myelodysplasia-related changes) were not accounted for: -9q, -12p, -13q, -13, t(12p), t(2;11), t(3;5), t(3;21), t(5;7), t(5;10), t(5;17), t(11;16), isochromosome(17q), idic(X)(q13), possibly resulting in a lower number of patients within this subgroup. In addition, the presence of prior chronic myelomonocytic leukaemia and prior myeloproliferative neoplasia was an exclusion criterion in the AML-001 trial, possibly resulting in a slightly lower number of patients within this subgroup; and <sup>c</sup> NCCN cytogenetic good risk was an exclusion criterion in the AZA-AML-001 trial. Two patients were included within the AAR had NCCN good risk cytogenetics.</p></fn></table-wrap-foot></table-wrap><table-wrap id="ijms-18-00415-t002" position="float"><object-id pub-id-type="pii">ijms-18-00415-t002_Table 2</object-id><label>Table 2</label><caption><p>Treatment characteristics of AML patients treated with azacitidine front-line per patient subset.</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="3" align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">Treatment Characteristics</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AML-001</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AAR</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AAR</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Trial</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(001-Like)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(WHO-AML)</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(<italic>n</italic> = 214)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(<italic>n</italic> = 95)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(<italic>n</italic> = 193)</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="1" colspan="1">AZA cycles, median, <italic>n</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">6</td><td align="center" valign="middle" rowspan="1" colspan="1">5</td><td align="center" valign="middle" rowspan="1" colspan="1">6</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> (Mean) [SD]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(8.4) [7.1]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(8.5) [9.1]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(8.4) [6.0]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">AZA cycles ≥6, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">50.0</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">46.3</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">51.3</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">AZA cycles ≥12, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">28.5</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">24.2</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">24.9</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Days of AZA application, median, days</td><td align="center" valign="middle" rowspan="1" colspan="1">42</td><td align="center" valign="middle" rowspan="1" colspan="1">34</td><td align="center" valign="middle" rowspan="1" colspan="1">39</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> (Mean) [SD]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(58.0) [49.8]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(55.8) [61.1]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(57.1) [57.3]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Daily of AZA dose, median, mg</td><td align="center" valign="middle" rowspan="1" colspan="1">130.1</td><td align="center" valign="middle" rowspan="1" colspan="1">131.6</td><td align="center" valign="middle" rowspan="1" colspan="1">132.0</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> (Mean) [SD]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(129.4) [17.8]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(128.7) [26.5]</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">(126.4) [33.3]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Reasons for AZA discontinuation, %</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> AE/no response/relapse/PD/death</td><td align="center" valign="middle" rowspan="1" colspan="1">66.8</td><td align="center" valign="middle" rowspan="1" colspan="1">74.8</td><td align="center" valign="middle" rowspan="1" colspan="1">73.1</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> Withdrew consent/patient’s wish</td><td align="center" valign="middle" rowspan="1" colspan="1">11.7</td><td align="center" valign="middle" rowspan="1" colspan="1">9.5</td><td align="center" valign="middle" rowspan="1" colspan="1">7.3</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"> Others</td><td align="center" valign="middle" rowspan="1" colspan="1">11.7</td><td align="center" valign="middle" rowspan="1" colspan="1">9.5</td><td align="center" valign="middle" rowspan="1" colspan="1">11.4</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Still on AZA at study closure</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.8</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.3</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8.3</td></tr></tbody></table></table-wrap><table-wrap id="ijms-18-00415-t003" position="float"><object-id pub-id-type="pii">ijms-18-00415-t003_Table 3</object-id><label>Table 3</label><caption><p>Outcome of AML patients treated with azacitidine front-line per patient subset.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcome</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AML-001 Trial (<italic>n</italic> = 214)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AAR (001-Like) (<italic>n</italic> = 95)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic>-Value</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AAR (001-Like) (<italic>n</italic> = 95)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">AAR (WHO-AML) (<italic>n</italic> = 193)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic>-Value</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">Median OS, mo</td><td align="center" valign="middle" rowspan="1" colspan="1">9.9</td><td align="center" valign="middle" rowspan="1" colspan="1">10.7</td><td align="center" valign="middle" rowspan="1" colspan="1">0.9553 <sup>a</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">10.7</td><td align="center" valign="middle" rowspan="1" colspan="1">11.8</td><td align="center" valign="middle" rowspan="1" colspan="1">0.599 <sup>a</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Median RFS (CR/CRi), mo</td><td align="center" valign="middle" rowspan="1" colspan="1">16.3</td><td align="center" valign="middle" rowspan="1" colspan="1">13.8</td><td align="center" valign="middle" rowspan="1" colspan="1">0.6817 <sup>a</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">13.8</td><td align="center" valign="middle" rowspan="1" colspan="1">13.3</td><td align="center" valign="middle" rowspan="1" colspan="1">0.621 <sup>a</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Median EFS (all pts), mo</td><td align="center" valign="middle" rowspan="1" colspan="1">6.9</td><td align="center" valign="middle" rowspan="1" colspan="1">8.3</td><td align="center" valign="middle" rowspan="1" colspan="1">0.2909 <sup>a</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">8.3</td><td align="center" valign="middle" rowspan="1" colspan="1">8.1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.941 <sup>a</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Median CR/CRi duration, mo</td><td align="center" valign="middle" rowspan="1" colspan="1">8.6</td><td align="center" valign="middle" rowspan="1" colspan="1">11.1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.1740 <sup>a</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">11.1</td><td align="center" valign="middle" rowspan="1" colspan="1">11.5</td><td align="center" valign="middle" rowspan="1" colspan="1">0.818 <sup>a</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">1-Year survival, %</td><td align="center" valign="middle" rowspan="1" colspan="1">54.2</td><td align="center" valign="middle" rowspan="1" colspan="1">53.7</td><td align="center" valign="middle" rowspan="1" colspan="1">0.843 <sup>b</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">53.7</td><td align="center" valign="middle" rowspan="1" colspan="1">50.8</td><td align="center" valign="middle" rowspan="1" colspan="1">0.476 <sup>b</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">30-Day mortality, %</td><td align="center" valign="middle" rowspan="1" colspan="1">7.0</td><td align="center" valign="middle" rowspan="1" colspan="1">8.4</td><td align="center" valign="middle" rowspan="1" colspan="1">0.924 <sup>b</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">8.4</td><td align="center" valign="middle" rowspan="1" colspan="1">7.8</td><td align="center" valign="middle" rowspan="1" colspan="1">0.848 <sup>b</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">ORR (CR, CRi, PR), %</td><td align="center" valign="middle" rowspan="1" colspan="1">30.4</td><td align="center" valign="middle" rowspan="1" colspan="1">18.9</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0379 <sup>b</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">18.9</td><td align="center" valign="middle" rowspan="1" colspan="1">23.1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.685 <sup>b</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">RBC-TI, %</td><td align="center" valign="middle" rowspan="1" colspan="1">39.3</td><td align="center" valign="middle" rowspan="1" colspan="1">42.1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.7522 <sup>b</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">42.1</td><td align="center" valign="middle" rowspan="1" colspan="1">42.2</td><td align="center" valign="middle" rowspan="1" colspan="1">0.517 <sup>b</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PLT-TI, %</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">37.2</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">35.7</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.0000 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">35.7</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">41.7</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.688 <sup>b</sup></td></tr></tbody></table><table-wrap-foot><fn><p><sup>a</sup> Median times for OS, RFS, EFS and CR/CRi duration were estimated by the KM method, and the <italic>p</italic>-value was based on the log-rank test; and <sup>b</sup> Calculated according to the χ-squared test for categorical variables and the <italic>t</italic>-test for continuous variable.</p></fn></table-wrap-foot></table-wrap><table-wrap id="ijms-18-00415-t004" position="float"><object-id pub-id-type="pii">ijms-18-00415-t004_Table 4</object-id><label>Table 4</label><caption><p>Univariate and multivariate analysis of the effects of baseline covariates on the OS of AML patients treated with azacitidine front-line with >30% BM blasts and <15 G/L WBC within the AZA-AML-001 trial and the AAR.</p></caption><table frame="hsides" rules="groups"><tbody><tr><td colspan="3" align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1"><bold>Univariate Analysis</bold></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Baseline Parameter</td><td align="center" valign="middle" rowspan="1" colspan="1">HR (95% CI)</td><td align="center" valign="middle" rowspan="1" colspan="1"><italic>p</italic>-Value</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Study group (AML-001 vs. AAR)</td><td align="center" valign="middle" rowspan="1" colspan="1">1.02 (0.78, 1.32)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.8998</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Age (as a continuous variable)</td><td align="center" valign="middle" rowspan="1" colspan="1">1.02 (1.00, 1.04)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0182</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Age (<75 vs. ≥75 years)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.70 (0.54, 0.90)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0053</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Gender (female vs. male)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.82 (0.64, 1.05)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.1243</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">RBC-TD (No vs. Yes)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.89 (0.69, 1.16)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.3857</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">PLT-TD (No vs. Yes)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.68 (0.53, 0.88)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0028</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">ECOG-PS (0–1 vs. ≥2)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.54 (0.41, 0.71)</td><td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">MDS-related changes present (Yes vs. No)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.90 (0.70, 1.16)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.4326</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Prior MDS (No vs. Yes)</td><td align="center" valign="middle" rowspan="1" colspan="1">1.01 (0.74, 1.38)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.9366</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">No. of cytopenias at baseline (0–1 vs. 2–3)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.83 (0.58, 1.19)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.3082</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">NCCN cytogenetic risk (Intermediate vs. Poor)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.51 (0.39, 0.66)</td><td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">BM blasts (30%–49% vs. ≥50%)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.90 (0.69, 1.18)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.4511</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">WBC (as a continuous variable)</td><td align="center" valign="middle" rowspan="1" colspan="1">1.00 (0.97, 1.04)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.8400</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">ANC (as a continuous variable)</td><td align="center" valign="middle" rowspan="1" colspan="1">1.05 (0.93, 1.17)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.4514</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">PLT count (as a continuous variable)</td><td align="center" valign="middle" rowspan="1" colspan="1">1.00 (1.00, 1.00)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.1487</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hb (as a continuous variable)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.96 (0.88, 1.05)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.3344</td></tr><tr><td colspan="3" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Multivariate Analysis</bold></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Baseline Covariate</td><td align="center" valign="middle" rowspan="1" colspan="1">HR (95% CI)</td><td align="center" valign="middle" rowspan="1" colspan="1"><italic>p</italic>-Value</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Age (<75 vs. ≥75 years)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.76 (0.58, 0.98)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0366</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">PLT-TD (No vs. Yes)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.69 (0.53, 0.90)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0057</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">ECOG-PS (0–1 vs. ≥2)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.65 (0.48, 0.87)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0041</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">NCCN cytogenetic risk (Intermediate vs. Poor)</td><td align="center" valign="middle" rowspan="1" colspan="1">0.51 (0.39, 0.67)</td><td align="center" valign="middle" rowspan="1" colspan="1"><0.001</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">AML-001 vs. AAR <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.11 (0.84, 1.47)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.4509</td></tr></tbody></table><table-wrap-foot><fn><p><bold><sup>a</sup></bold> As this covariate was the variable most critical to the intended analysis, it was kept in the final multivariate analysis model.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Autriche</li></country></list><tree><noCountry><name sortKey="Andel, Johannes" sort="Andel, Johannes" uniqKey="Andel J" first="Johannes" last="Andel">Johannes Andel</name><name sortKey="Autzinger, Eva M" sort="Autzinger, Eva M" uniqKey="Autzinger E" first="Eva M." last="Autzinger">Eva M. Autzinger</name><name sortKey="Beach, Cl" sort="Beach, Cl" uniqKey="Beach C" first="Cl" last="Beach">Cl Beach</name><name sortKey="Burgstaller, Sonja" sort="Burgstaller, Sonja" uniqKey="Burgstaller S" first="Sonja" last="Burgstaller">Sonja Burgstaller</name><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><name sortKey="Dombret, Herve" sort="Dombret, Herve" uniqKey="Dombret H" first="Hervé" last="Dombret">Hervé Dombret</name><name sortKey="Geissler, Klaus" sort="Geissler, Klaus" uniqKey="Geissler K" first="Klaus" last="Geissler">Klaus Geissler</name><name sortKey="Girschikofsky, Michael" sort="Girschikofsky, Michael" uniqKey="Girschikofsky M" first="Michael" last="Girschikofsky">Michael Girschikofsky</name><name sortKey="Halter, Britta" sort="Halter, Britta" uniqKey="Halter B" first="Britta" last="Halter">Britta Halter</name><name sortKey="Hojas, Sabine" sort="Hojas, Sabine" uniqKey="Hojas S" first="Sabine" last="Hojas">Sabine Hojas</name><name sortKey="Lang, Alois" sort="Lang, Alois" uniqKey="Lang A" first="Alois" last="Lang">Alois Lang</name><name sortKey="Machherndl Spandl, Sigrid" sort="Machherndl Spandl, Sigrid" uniqKey="Machherndl Spandl S" first="Sigrid" last="Machherndl Spandl">Sigrid Machherndl Spandl</name><name sortKey="Pfeilstocker, Michael" sort="Pfeilstocker, Michael" uniqKey="Pfeilstocker M" first="Michael" last="Pfeilstöcker">Michael Pfeilstöcker</name><name sortKey="Pichler, Angelika" sort="Pichler, Angelika" uniqKey="Pichler A" first="Angelika" last="Pichler">Angelika Pichler</name><name sortKey="Rogulj, Inga M" sort="Rogulj, Inga M" uniqKey="Rogulj I" first="Inga M." last="Rogulj">Inga M. Rogulj</name><name sortKey="Schlick, Konstantin" sort="Schlick, Konstantin" uniqKey="Schlick K" first="Konstantin" last="Schlick">Konstantin Schlick</name><name sortKey="Schuh, Andre C" sort="Schuh, Andre C" uniqKey="Schuh A" first="Andre C." last="Schuh">Andre C. Schuh</name><name sortKey="Seymour, John F" sort="Seymour, John F" uniqKey="Seymour J" first="John F." last="Seymour">John F. Seymour</name><name sortKey="Sill, Heinz" sort="Sill, Heinz" uniqKey="Sill H" first="Heinz" last="Sill">Heinz Sill</name><name sortKey="Sperr, Wolfgang R" sort="Sperr, Wolfgang R" uniqKey="Sperr W" first="Wolfgang R." last="Sperr">Wolfgang R. Sperr</name><name sortKey="Stauder, Reinhard" sort="Stauder, Reinhard" uniqKey="Stauder R" first="Reinhard" last="Stauder">Reinhard Stauder</name><name sortKey="Swern, Arlene S" sort="Swern, Arlene S" uniqKey="Swern A" first="Arlene S." last="Swern">Arlene S. Swern</name><name sortKey="Thaler, Josef" sort="Thaler, Josef" uniqKey="Thaler J" first="Josef" last="Thaler">Josef Thaler</name><name sortKey="Voskova, Daniela" sort="Voskova, Daniela" uniqKey="Voskova D" first="Daniela" last="Voskova">Daniela Voskova</name><name sortKey="Zebisch, Armin" sort="Zebisch, Armin" uniqKey="Zebisch A" first="Armin" last="Zebisch">Armin Zebisch</name></noCountry><country name="Autriche"><noRegion><name sortKey="Pleyer, Lisa" sort="Pleyer, Lisa" uniqKey="Pleyer L" first="Lisa" last="Pleyer">Lisa Pleyer</name></noRegion><name sortKey="Greil, Richard" sort="Greil, Richard" uniqKey="Greil R" first="Richard" last="Greil">Richard Greil</name><name sortKey="Greil, Richard" sort="Greil, Richard" uniqKey="Greil R" first="Richard" last="Greil">Richard Greil</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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