TY  - JOUR
A1  - Stölzel, F.
A1  - Mohr, B.
A1  - Kramer, M.
A1  - Oelschlägel, U.
A1  - Bochtler, T.
A1  - Berdel, W. E.
A1  - Kaufmann, M.
A1  - Baldus, C. D.
A1  - Schäfer-Eckart, K.
A1  - Stuhlmann, R.
A1  - Einsele, H.
A1  - Krause, S. W.
A1  - Serve, H.
A1  - Hänel, M.
A1  - Herbst, R.
A1  - Neubauer, A.
A1  - Sohlbach, K.
A1  - Mayer, J.
A1  - Middeke, J. M.
A1  - Platzbecker, U.
A1  - Schaich, M.
A1  - Krämer, A.
A1  - Röllig, C.
A1  - Schetelig, J.
A1  - Bornhäuser, M.
A1  - Ehninger, G.
T1  - Karyotype complexity and prognosis in acute myeloid leukemia
JF  - Blood Cancer Journal
N2  - A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with 4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.
KW  - Cancer genetics
KW  - Genetics research
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164530
VL  - 6
ER  - 
TY  - JOUR
A1  - Eckardt, Jan-Niklas
A1  - Stasik, Sebastian
A1  - Kramer, Michael
A1  - Röllig, Christoph
A1  - Krämer, Alwin
A1  - Scholl, Sebastian
A1  - Hochhaus, Andreas
A1  - Crysandt, Martina
A1  - Brümmendorf, Tim H.
A1  - Naumann, Ralph
A1  - Steffen, Björn
A1  - Kunzmann, Volker
A1  - Einsele, Hermann
A1  - Schaich, Markus
A1  - Burchert, Andreas
A1  - Neubauer, Andreas
A1  - Schäfer-Eckart, Kerstin
A1  - Schliemann, Christoph
A1  - Krause, Stefan W.
A1  - Herbst, Regina
A1  - Hänel, Mathias
A1  - Frickhofen, Norbert
A1  - Noppeney, Richard
A1  - Kaiser, Ulrich
A1  - Baldus, Claudia D.
A1  - Kaufmann, Martin
A1  - Rácil, Zdenek
A1  - Platzbecker, Uwe
A1  - Berdel, Wolfgang E.
A1  - Mayer, Jiří
A1  - Serve, Hubert
A1  - Müller-Tidow, Carsten
A1  - Ehninger, Gerhard
A1  - Stölzel, Friedrich
A1  - Kroschinsky, Frank
A1  - Schetelig, Johannes
A1  - Bornhäuser, Martin
A1  - Thiede, Christian
A1  - Middeke, Jan Moritz
T1  - Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia
JF  - Cancers
N2  - Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
KW  - acute myeloid leukemia
KW  - BCOR
KW  - BCORL1
KW  - loss-of-function
KW  - risk stratification
KW  - survival
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236735
SN  - 2072-6694
VL  - 13
IS  - 9
ER  - 
TY  - JOUR
A1  - Röllig, C.
A1  - Kramer, M.
A1  - Gabrecht, M.
A1  - Hänel, M.
A1  - Herbst, R.
A1  - Kaiser, U.
A1  - Schmitz, N.
A1  - Kullmer, J.
A1  - Fetscher, S.
A1  - Link, H.
A1  - Mantovani-Löffler, L.
A1  - Krümpelmann, U.
A1  - Neuhaus, T.
A1  - Heits, F.
A1  - Einsele, H.
A1  - Ritter, B.
A1  - Bornhäuser, M.
A1  - Schetelig, J.
A1  - Thiede, C.
A1  - Mohr, B.
A1  - Schaich, M.
A1  - Platzbecker, U.
A1  - Schäfer-Eckart, K.
A1  - Krämer, A.
A1  - Berdel, W. E.
A1  - Serve, H.
A1  - Ehninger, G.
A1  - Schuler, U. S.
T1  - Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients
JF  - Annals of Oncology
N2  - Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7+3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). 

Patients and methods: Patients with newly diagnosed AML>60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m(2) twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m(2) days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m(2) continuously days 1-7) plus daunorubicin (45 mg/m(2) days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. 

Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). 

Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
KW  - acute myeloid leukemia
KW  - cytarabine dose
KW  - elderly
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226473
VL  - 29
IS  - 4
ER  -