TY  - JOUR
A1  - Schlenk, Richard Friedrich
A1  - Lübbert, Michael
A1  - Benner, Axel
A1  - Lamparter, Alexander
A1  - Krauter, Jürgen
A1  - Herr, Wolfgang
A1  - Martin, Hans
A1  - Salih, Helmut Rainer
A1  - Kündgen, Andrea
A1  - Horst, Heinz August
A1  - Brossart, Peter
A1  - Götze, Katharina
A1  - Nachbaur, David
A1  - Wattad, Mohammed
A1  - Köhne, Claus-Henning
A1  - Fiedler, Walter
A1  - Bentz, Martin
A1  - Wulf, Gerald
A1  - Held, Gerhard
A1  - Hertenstein, Bernd
A1  - Salwender, Hans
A1  - Gaidzik, Verena I.
A1  - Schlegelberger, Brigitte
A1  - Weber, Daniela
A1  - Döhner, Konstanze
A1  - Ganser, Arnold
A1  - Döhner, Hartmut
T1  - All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia : results of the randomized AMLSG 07-04 study
T2  - Annals of hematology
N2  - The 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/m2, days 6-8; 15 mg/m2, 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).
KW  - Acute myeloid leukemia
KW  - All-trans retinoic acid
KW  - Nucleophosmin-1
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42740
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-427401
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093206
SN  - 1432-0584
SN  - 0939-5555
N1  - This article is distributed under the terms of the Creative Commons At tribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Electronic supplementary material: The online version of this article (doi:10.1007/s00277-016-2810-z) contains supplementary material, which is available to authorized users.
VL  - 95
IS  - 12
SP  - 1931
EP  - 1942
PB  - Springer
CY  - Berlin ; Heidelberg ; New York
ER  -