TY  - JOUR
A1  - Middeke, Jan Moritz
A1  - Metzeler, Klaus Hans
A1  - Röllig, Christoph
A1  - Krämer, Michael
A1  - Eckardt, Jan-Niklas
A1  - Stasik, Sebastian
A1  - Greif, Philipp
A1  - Spiekermann, Karsten
A1  - Rothenberg-Thurley, Maja
A1  - Krug, Utz
A1  - Braess, Jan
A1  - Krämer, Alwin
A1  - Hochhaus, Andreas
A1  - Brümmendorf, Tim Henrik
A1  - Naumann, Ralph
A1  - Steffen, Björn
A1  - Einsele, Hermann
A1  - Schaich, Markus
A1  - Burchert, Andreas
A1  - Neubauer, Andreas
A1  - Görlich, Dennis
A1  - Sauerland, Cristina
A1  - Schäfer-Eckart, Kerstin
A1  - Schliemann, Christoph
A1  - Krause, Stefan W.
A1  - Hänel, Mathias
A1  - Frickhofen, Norbert
A1  - Noppeney, Richard
A1  - Kaiser, Ulrich
A1  - Kaufmann, Martin
A1  - Kunadt, Désirée
A1  - Wörmann, Bernhard
A1  - Sockel, Katja
A1  - Bonin, von Malte
A1  - Herold, Tobias
A1  - Müller-Tidow, Carsten
A1  - Platzbecker, Uwe
A1  - Berdel, Wolfgang E.
A1  - Serve, Hubert
A1  - Baldus, Claudia
A1  - Ehninger, Gerhard
A1  - Schetelig, Johannes
A1  - Hiddemann, Wolfgang
A1  - Bornhäuser, Martin
A1  - Stölzel, Friedrich
A1  - Thiede, Christian
T1  - Differential impact of IDH1/2 mutational subclasses on outcome in adult AML: results from a large multicenter study
T2  - Blood advances
N2  - Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
KW  - Clinical Trials and Observations
KW  - Myeloid Neoplasia
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63110
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-631109
SN  - 2473-9537
VL  - 6
IS  - 5
SP  - 1394
EP  - 1405
PB  - American Society of Hematology
CY  - Washington, DC
ER  -