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Verfasst von:Wermke, Martin [VerfasserIn]   i
 Nolte, Florian [VerfasserIn]   i
 Hofmann, Wolf-Karsten [VerfasserIn]   i
Titel:Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity
Titelzusatz:results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS)
Verf.angabe:Martin Wermke, Claudia Schuster, Florian Nolte, Haifa-Kathrin Al-Ali, Philipp Kiewe, Claudia Schönefeldt, Christiane Jakob, Malte von Bonin, Leopold Hentschel, Ina-Maria Klut, Gerhard Ehninger, Martin Bornhäuser, Gustavo Baretton, Ulrich Germing, Regina Herbst, Detelef Haase, Wolf K. Hofmann, Uwe Platzbecker
E-Jahr:2016
Jahr:7 October 2016
Umfang:8 S.
Fussnoten:Gesehen am 02.11.2017
Titel Quelle:Enthalten in: British journal of haematology
Ort Quelle:Oxford [u.a.] : Wiley-Blackwell, 1955
Jahr Quelle:2016
Band/Heft Quelle:175(2016), 5, Seite 917-924
ISSN Quelle:1365-2141
Abstract:The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower- and 11 higher-risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival (OS) was not reached in the lower-risk group and 296 days in the higher-risk group. We observed a significant decline of bone marrow (BM) vascularisation (P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro-inflammatory T-helper-cell subsets within the peripheral blood or BM. We conclude that mTOR-modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients.
DOI:doi:10.1111/bjh.14345
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1111/bjh.14345
 Volltext: http://onlinelibrary.wiley.com/doi/10.1111/bjh.14345/abstract
 DOI: https://doi.org/10.1111/bjh.14345
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:mTOR modulation
 myelodysplastic syndromes
 regulatory T-cell
 temsirolimus
 vascularization
K10plus-PPN:1564958442
Verknüpfungen:→ Zeitschrift

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