12157
2014
eng
1167-76
7
93
article
for the German Chronic Myeloid Leukemia Study Group, and the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK)
1
2015-11-02
--
--
Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV
The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
Annals of Hematology
10.1007/s00277-014-2041-0
0939-5555
24658964
urn:nbn:de:bvb:20-opus-121574
Annals of Hematology (2014) 93:1167–1176 DOI 10.1007/s00277-014-2041-0
Ulrike Proetel
Nadine Pletsch
Michael Lauseker
Martin C. Müller
Benjamin Hanfstein
Stefan W. Krause
Lida Kalmanti
Annette Schreiber
Dominik Heim
Gabriela M. Baerlocher
Wolf-Karsten Hofmann
Elisabeth Lange
Hermann Einsele
Martin Wernli
Stephan Kremers
Rudolf Schlag
Lothar Müller
Mathias Hänel
Hartmut Link
Bernd Hertenstein
Markus Pfirrmann
Andreas Hochhaus
Joerg Hasford
Rüdiger Hehlmann
Susanne Saußele
eng
uncontrolled
chronic myeloid leukemia
eng
uncontrolled
older patients
eng
uncontrolled
different imatinib dose regimens
eng
uncontrolled
early applied higher imatinib dosages
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12157/053_Proetel_Annals_of_Hematology.pdf
11547
2014
eng
1441-1447
9
99
article
1
2015-07-07
--
--
Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib
The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 x 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 x 109/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier: 00055874)
Haematologica
10.3324/haematol.2013.096537
1592-8721
24837466
urn:nbn:de:bvb:20-opus-115476
Haematologica 2014 99(9) 1441-1447. DOI 10.3324/haematol.2013.096537
Deutsches Urheberrecht
Benjamin Hanfstein
Michael Lauseker
Rüdiger Hehlmann
Susanne Saussele
Philipp Erben
Christian Dietz
Alice Fabarius
Ulrike Proetel
Susanne Schnittger
Claudia Haferlach
Stefan W. Krause
Jörg Schubert
Hermann Einsele
Mathias Hänel
Jolanta Dengler
Christiane Falge
Lothar Kanz
Andreas Neubauer
Michael Kneba
Frank Stengelmann
Michael Pfreundschuh
Cornelius F. Waller
Karsten Spiekerman
Gabriela M. Baerlocher
Markus Pfirrmann
Joerg Hasford
Wolf-Karsten Hofmann
Andreas Hochhaus
Martin C. Müller
eng
uncontrolled
chronic myelogenous leukemia
eng
uncontrolled
polymerase-chain-reaktion
eng
uncontrolled
hybrid messenger RNA
eng
uncontrolled
chronic phase
eng
uncontrolled
cytogenetic response
eng
uncontrolled
no correlation
eng
uncontrolled
ABL gene
eng
uncontrolled
transcripts
eng
uncontrolled
breakpoint
eng
uncontrolled
survival
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11547/051_Hanfstein_Haematologica_full.pdf
https://opus.bibliothek.uni-wuerzburg.de/files/11547/051_Hanfstein_Haematologica.pdf
23673
2021
eng
9
13
article
1
--
2021-04-26
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Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia
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.
Cancers
2072-6694
10.3390/cancers13092095
urn:nbn:de:bvb:20-opus-236735
2021-05-03T18:32:27+00:00
sword
swordwue
attachment; filename=deposit.zip
dc3f35ae8ed1fb85a3af2b7df56e410e
Cancers (2021) 13:9, 2095. https://doi.org/10.3390/cancers13092095
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Jan-Niklas Eckardt
Sebastian Stasik
Michael Kramer
Christoph Röllig
Alwin Krämer
Sebastian Scholl
Andreas Hochhaus
Martina Crysandt
Tim H. Brümmendorf
Ralph Naumann
Björn Steffen
Volker Kunzmann
Hermann Einsele
Markus Schaich
Andreas Burchert
Andreas Neubauer
Kerstin Schäfer-Eckart
Christoph Schliemann
Stefan W. Krause
Regina Herbst
Mathias Hänel
Norbert Frickhofen
Richard Noppeney
Ulrich Kaiser
Claudia D. Baldus
Martin Kaufmann
Zdenek Rácil
Uwe Platzbecker
Wolfgang E. Berdel
Jiří Mayer
Hubert Serve
Carsten Müller-Tidow
Gerhard Ehninger
Friedrich Stölzel
Frank Kroschinsky
Johannes Schetelig
Martin Bornhäuser
Christian Thiede
Jan Moritz Middeke
eng
uncontrolled
acute myeloid leukemia
eng
uncontrolled
BCOR
eng
uncontrolled
BCORL1
eng
uncontrolled
loss-of-function
eng
uncontrolled
risk stratification
eng
uncontrolled
survival
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik II
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23673/cancers-13-02095-v2.pdf