TY  - JOUR
AU  - Schlenk, Richard
AU  - Lübbert, Michael
AU  - Benner, Axel
AU  - Lamparter, Alexander
AU  - Krauter, Jürgen
AU  - Herr, Wolfgang
AU  - Martin, Hans
AU  - Salih, Helmut R
AU  - Kündgen, Andrea
AU  - Horst, Heinz-A
AU  - Brossart, Peter
AU  - Götze, Katharina
AU  - Nachbaur, David
AU  - Wattad, Mohammed
AU  - Köhne, Claus-Henning
AU  - Fiedler, Walter
AU  - Bentz, Martin
AU  - Wulf, Gerald
AU  - Held, Gerhard
AU  - Hertenstein, Bernd
AU  - Salwender, Hans
AU  - Gaidzik, Verena I
AU  - Schlegelberger, Brigitte
AU  - Weber, Daniela
AU  - Döhner, Konstanze
AU  - Ganser, Arnold
AU  - Döhner, Hartmut
TI  - 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.
JO  - Annals of hematology
VL  - 95
IS  - 12
SN  - 0939-5555
CY  - Berlin
PB  - Springer61936
M1  - DKFZ-2017-05570
SP  - 1931-1942
PY  - 2016
AB  - 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/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).
KW  - Tretinoin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27696203
C2  - pmc:PMC5093206
DO  - DOI:10.1007/s00277-016-2810-z
UR  - https://inrepo02.dkfz.de/record/130491
ER  -