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  - 
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  -