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    Wyświetlanie 1-6 z 6
    Tytuł:
    Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin
    Autorzy:
    Lauseker, Michael
    Hochhaus, Andreas
    Olsson-Stromberg, Ulla
    Clark, Richard E.
    Ossenkoppele, Gert Ossenkoppele
    Heibl, Sonja
    Hasford, Joerg
    Griskevicius, Laimonas
    Faber, Edgar
    Sacha, Tomasz
    Baccarani, Michele
    Koskenvesa, Perttu
    Bachl, Katharina
    Schubert-Fritschle, Gabriele
    Pfirrmann, Markus
    Turkina, Anna
    Prejzner, Witold
    Guilhot, Joelle
    Zackova, Daniela
    Bogdanovic, Andrija
    Lomaia, Elza
    Hoffmann, Verena S.
    Opis:
    Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population‐based and out‐study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20‐29% blasts, the hazard ratio (HR) was 1.32 (95%‐confidence interval (CI): [0.7‐2.6]). Patients with 20‐29% blasts had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%‐CI: [1.2‐4.0], P = .008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs non‐high risk) with an HR of 3.01 (95%‐CI: [1.81‐5.00], P < .001). Regarding the contrasting definitions of blast crisis, our data clearly supported the 20% cut‐off over the 30% cut‐off in this cohort. Based on our results, we conclude that a one‐phase rather than a two‐phase categorization of de novo advanced phase CML patients is appropriate.
    Dostawca treści:
    Repozytorium Uniwersytetu Jagiellońskiego
    Artykuł
    Tytuł:
    The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib
    Autorzy:
    Fabarius, Alice
    Waller, Cornelius F.
    Faber, Edgar
    Curik, Nikola
    Grzybowska-Izydorczyk, Olga
    Mustjoki, Satu
    Klamova, Hana
    Hjorth-Hansen, Henrik
    Płonka-Stępień, Magdalena
    Bober, Grażyna
    Vlcanova, Katerina
    Spiess, Birgit
    Albeer, Ali
    Belohlavkova, Petra
    Niesiobędzka-Krężel, Joanna
    Wasilewska, Ewa
    Szczepanek, Elżbieta
    Richter, Johan
    Mahon, Francois-Xavier
    Kamińska, Magdalena
    Szarejko, Monika
    Burchert, Andreas
    Paczkowska, Edyta
    Pfirrmann, Markus
    Saußele, Susanne
    Kunzmann, Volker
    Polivkova, Vaclava
    Machova Polakova, Katerina
    Sacha, Tomasz
    Krutska, Monika
    Mayer, Jiri
    Zackova, Daniela
    Panayiotidis, Panayiotis
    Brümmendorf, Tim H.
    Hus, Iwona
    Giannopoulos, Krzysztof
    Dengler, Jolanta
    Opis:
    Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60–82%) compared to patients with GG (51%, 95% CI: 41–61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.
    Dostawca treści:
    Repozytorium Uniwersytetu Jagiellońskiego
    Artykuł
      Wyświetlanie 1-6 z 6

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