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Berlin Brandenburg

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  • 1
    Language: English
    In: Annals of Hematology, 21 July 2010, Vol.90(4), pp.473-475
    Description: Dear Editor, We report on two patients with acute myeloid leukemia (AML) initially presenting in 2007. Both patients were tested positive for the FLT3-ITD mutation and were therefore treated with the FLT3 tyrosine kinase inhibitor sorafenib (400 mg/day) after progress of AML following several protocols of conventional chemotherapy. Both patients responded with a significant reduction of peripheral blast counts after 10 to 17 days leading to hematological response for 12 and 14 weeks, respectively. At the time of relapse, molecular analysis investigating mutations of both tyrosine kinase domains by sequencing of each individual FLT3-ITD cDNA did not demonstrate any additional mutations. We therefore suggest that the secondary resistance to sorafenib is mediated by other mechanisms than the acquisition of secondary mutations of FLT3 in these patients. FLT3-ITD mutations represent the second most frequent molecular aberration in AML leading to a constitutive activity of the class III receptor tyrosine kinase FLT3. FLT3-ITD mutations can be found in 25–30% of all AML patients and are associated with a reduced disease-free survival and overall survival [1–3].
    Keywords: Medicine ; Medicine
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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  • 2
    Language: English
    In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 10 September 2009, Vol.27(26), pp.4378-84
    Description: This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL). Patients (〈or= 75 years of age) were randomly assigned to receive bendamustine 100 mg/m(2)/d intravenously on days 1 to 2, or chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee. A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P 〈 .0001). More patients showed complete responses with bendamustine than with chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P 〈 .0001). Bendamustine was also associated with an improvement in duration of remission, compared with chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients. Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.
    Keywords: Chlorambucil -- Therapeutic Use ; Leukemia, Lymphocytic, Chronic, B-Cell -- Drug Therapy ; Nitrogen Mustard Compounds -- Therapeutic Use
    E-ISSN: 1527-7755
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