@article{RoelligKramerGabrechtetal.2018,
  author    = {R{\"o}llig, C. and Kramer, M. and Gabrecht, M. and H{\"a}nel, M. and Herbst, R. and Kaiser, U. and Schmitz, N. and Kullmer, J. and Fetscher, S. and Link, H. and Mantovani-L{\"o}ffler, L. and Kr{\"u}mpelmann, U. and Neuhaus, T. and Heits, F. and Einsele, H. and Ritter, B. and Bornh{\"a}user, M. and Schetelig, J. and Thiede, C. and Mohr, B. and Schaich, M. and Platzbecker, U. and Sch{\"a}fer-Eckart, K. and Kr{\"a}mer, A. and Berdel, W. E. and Serve, H. and Ehninger, G. and Schuler, U. S.},
  title     = {Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients},
  series = {Annals of Oncology},
  volume    = {29},
  journal   = {Annals of Oncology},
  number    = {4},
  doi       = {doi:10.1093/annonc/mdy030},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226473},
  pages     = {973-978},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{StoelzelMohrKrameretal.2016,
  author    = {St{\"o}lzel, F. and Mohr, B. and Kramer, M. and Oelschl{\"a}gel, U. and Bochtler, T. and Berdel, W. E. and Kaufmann, M. and Baldus, C. D. and Sch{\"a}fer-Eckart, K. and Stuhlmann, R. and Einsele, H. and Krause, S. W. and Serve, H. and H{\"a}nel, M. and Herbst, R. and Neubauer, A. and Sohlbach, K. and Mayer, J. and Middeke, J. M. and Platzbecker, U. and Schaich, M. and Kr{\"a}mer, A. and R{\"o}llig, C. and Schetelig, J. and Bornh{\"a}user, M. and Ehninger, G.},
  title     = {Karyotype complexity and prognosis in acute myeloid leukemia},
  series = {Blood Cancer Journal},
  volume    = {6},
  journal   = {Blood Cancer Journal},
  doi       = {10.1038/bcj.2015.114},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164530},
  pages     = {e386},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{EckardtStasikKrameretal.2021,
  author    = {Eckardt, Jan-Niklas and Stasik, Sebastian and Kramer, Michael and R{\"o}llig, Christoph and Kr{\"a}mer, Alwin and Scholl, Sebastian and Hochhaus, Andreas and Crysandt, Martina and Br{\"u}mmendorf, Tim H. and Naumann, Ralph and Steffen, Bj{\"o}rn and Kunzmann, Volker and Einsele, Hermann and Schaich, Markus and Burchert, Andreas and Neubauer, Andreas and Sch{\"a}fer-Eckart, Kerstin and Schliemann, Christoph and Krause, Stefan W. and Herbst, Regina and H{\"a}nel, Mathias and Frickhofen, Norbert and Noppeney, Richard and Kaiser, Ulrich and Baldus, Claudia D. and Kaufmann, Martin and R{\´a}cil, Zdenek and Platzbecker, Uwe and Berdel, Wolfgang E. and Mayer, Jiř{\´i} and Serve, Hubert and M{\"u}ller-Tidow, Carsten and Ehninger, Gerhard and St{\"o}lzel, Friedrich and Kroschinsky, Frank and Schetelig, Johannes and Bornh{\"a}user, Martin and Thiede, Christian and Middeke, Jan Moritz},
  title     = {Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {9},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13092095},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236735},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}