Schlenk, Richard F.Richard F.SchlenkLuebbert, MichaelMichaelLuebbertBenner, AxelAxelBennerLamparter, AlexanderAlexanderLamparterKrauter, JuergenJuergenKrauterHerr, WolfgangWolfgangHerrMartin, HansHansMartinSalih, Helmut R.Helmut R.SalihKuendgen, AndreaAndreaKuendgenHorst, Heinz-AugustHeinz-AugustHorstBrossart, PeterPeterBrossartGoetze, Katharina S.Katharina S.GoetzeNachbaur, DavidDavidNachbaurWattad, MohammedMohammedWattadKoehne, Claus-HenningClaus-HenningKoehneFiedler, WalterWalterFiedlerBentz, MartinMartinBentzWulf, GeraldGeraldWulfHeld, GerhardGerhardHeldHertenstein, BerndBerndHertensteinSalwender, HansHansSalwenderGaidzik, Verena I.Verena I.GaidzikSchlegelberger, BrigitteBrigitteSchlegelbergerWeber, DanielaDanielaWeberDoehner, KonstanzeKonstanzeDoehnerGanser, ArnoldArnoldGanserDoehner, HartmutHartmutDoehner2018-11-072018-11-072016https://resolver.sub.uni-goettingen.de/purl?gro-2/38910The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m(2), days 6-8; 15 mg/m(2), days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).CC BY 4.0https://creativecommons.org/licenses/by/4.0journal_article10.1007/s00277-016-2810-z27696203000387354000001https://resolver.sub.uni-goettingen.de/purl?gs-1/14163