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Institute
Middeke, Jan Moritz ; Metzeler, Klaus Hans ; Röllig, Christoph ; Krämer, Michael ; Eckardt, Jan-Niklas ; Stasik, Sebastian ; Greif, Philipp ; Spiekermann, Karsten ; Rothenberg-Thurley, Maja ; Krug, Utz ; Braess, Jan ; Krämer, Alwin ; Hochhaus, Andreas ; Brümmendorf, Tim Henrik ; Naumann, Ralph ; Steffen, Björn ; Einsele, Hermann ; Schaich, Markus ; Burchert, Andreas ; Neubauer, Andreas ; Görlich, Dennis ; Sauerland, Cristina ; Schäfer-Eckart, Kerstin ; Schliemann, Christoph ; Krause, Stefan W. ; Hänel, Mathias ; Frickhofen, Norbert ; Noppeney, Richard ; Kaiser, Ulrich ; Kaufmann, Martin ; Kunadt, Désirée ; Wörmann, Bernhard ; Sockel, Katja ; Bonin, von Malte ; Herold, Tobias ; Müller-Tidow, Carsten ; Platzbecker, Uwe ; Berdel, Wolfgang E. ; Serve, Hubert ; Baldus, Claudia ; Ehninger, Gerhard ; Schetelig, Johannes ; Hiddemann, Wolfgang ; Bornhäuser, Martin ; Stölzel, Friedrich ; Thiede, Christian
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.
Koschade-Rixner, Sebastian E. ; Stratmann, Jan Alexander ; Finkelmeier, Fabian ; Wagner, Sebastian ; Chromik, Jörg ; Steffen, Björn ; Serve, Hubert ; Brandts, Christian Hubertus ; Ballo, Olivier Karl Friedrich
The optimal follow-up care for relapse detection in acute myeloid leukemia (AML) patients in first remission after consolidation therapy with intensive chemotherapy is not established. In this retrospective study, we evaluate the diagnostic value of an intensive relapse surveillance strategy by regular bone marrow aspirations (BMA) in these patients. We identified 86 patients with newly diagnosed non-promyelocytic AML who had reached complete remission (CR) after intensive induction and consolidation chemotherapy between 2007 and 2019. Annual relapse rates were 40%, 17%, and 2% in years 1–3, respectively. Patients in CR were surveilled by BMA scheduled every 3 months for 2 years, followed by BMA every 6 months. This surveillance regimen detected 29 of 55 relapses (53%), 11 of which were molecular relapses (20%). The remaining 26 of 55 relapses (47%) were diagnosed by non-surveillance BMA prompted by specific suspicion of relapse. Most patients showed concurrent morphological abnormalities in peripheral blood (PB) at time of relapse. Seven percent of all morphological relapses occurred without simultaneous PB abnormalities and would have been delayed without surveillance BMA. Intensified monthly PB assessment paired with BMA every 3 months during the first 2 years may be a highly sensitive relapse surveillance strategy.