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Berlin Brandenburg

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  • 1
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2009, Vol.135(4), pp.491-505
    Description: The role of different cytogenetic changes has been extensively evaluated in patients with acute myeloid leukemia (AML), and cytogenetic analysis of AML blasts is essential to form prognostic subgroups in order to stratify for the extent of therapy. Nevertheless, 40–45% of AML patients lack such cytogenetic markers, i.e., cytogenetically normal AML (CN-AML). In the past decade, different molecular aberrations were identified in AML and especially CN-AML can now be discriminated into certain prognostic subgroups. This review considers the latest advances to define the prognostic impact of molecular aberrations in AML and gives insights how such molecular markers can be applied for analysis of minimal residual disease. Furthermore, therapeutic implications as well as the potential role of new methodological techniques in analyzing expression patterns of AML blasts are discussed.
    Keywords: AML ; MRD ; Mutations ; Prognosis
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 2
    In: European Journal of Haematology, March 2008, Vol.80(3), pp.208-215
    Description: Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3‐ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AML patients, Flt3‐ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients. We retrospectively analysed the prevalence of NPM1 and Flt3‐ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60–85 yr) newly diagnosed for AML. Primary treatment approach was curative in 54, and palliative in 38 patients, while seven patients received best supportive care only. The mean follow‐up of surviving patients was 600 d. Sixty‐seven patients were tested negative for NPM1 and Flt3‐ITD mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine patients had only a Flt3‐ITD mutation (group 3) while additional seven patients were positive for both aberrations (group 4). We can demonstrate a significant higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group 1 vs. 80.0% for group 2,  = 0.03) for patients receiving curative therapy. Interestingly, there is no significant difference in overall survival between group 1 and group 2 (Log‐rank test  = 0.22, median 440 d vs. 1125 d). In contrast, patients carrying a Flt3‐ITD mutation had a significant worse overall survival compared to wildtype patients ( = 0.03, median 210 d for group 3 + 4 vs. 634 d for group 1 + 2) while no difference of CR rate could be observed (42.8% vs. 48.9%,  = 0.91). As elderly but medically fit patients with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a barrier for induction treatment. However, new therapeutic concepts of postremission therapy (e.g. allogeneic stem cell transplantation after dose‐reduced conditioning) should be considered for these patients in first CR.
    Keywords: Aml ; Npm1 ; Flt3‐Itd ; Elderly Patients ; Prognosis
    ISSN: 0902-4441
    E-ISSN: 1600-0609
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