Wolfgang E Berdel

University of Münster, Muenster, North Rhine-Westphalia, Germany

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Publications (511)2736.81 Total impact

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    ABSTRACT: Apoptosis is a crucial pathway in tumor growth and metastatic development. Apoptotic proteins regulate the underlying molecular cascades and are thought to modulate the tumor response to chemotherapy and radiation. However, the prognostic value of the expression of apoptosis regulators in localized non-small-cell lung cancer (NSCLC) is still unclear.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2014; · 4.55 Impact Factor
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    ABSTRACT: Isolated trisomy 13 (AML+13) is a rare chromosomal abnormality in acute myeloid leukemia (AML), and its prognostic relevance is poorly characterized. We analyzed the clinical course of 34 AML+13 patients enrolled in the German AMLCG-1999 and SAL trials and studied their biological characteristics by exome sequencing, targeted sequencing of candidate genes and gene expression profiling. Relapse-free (RFS) and overall survival (OS) of AML+13 patients were inferior compared to other ELN Intermediate-II patients (n=855) (median RFS, 7.8 vs 14.1 months, p=0.006; median OS 9.3 vs. 14.8 months, p=0.004). Besides the known high frequency of RUNX1 mutations (75%), we identified mutations in spliceosome components in 88%, including SRSF2 codon 95 mutations in 81%, of AML+13 patients. Moreover, recurring mutations were detected in ASXL1 (44%) and BCOR (25%). Two patients carried mutations in CEBPZ, suggesting that CEBPZ is a novel recurrently mutated gene in AML. Gene expression analysis revealed a homogenous expression profile including upregulation of FOXO1 and FLT3 and downregulation of SPRY2. This is the most comprehensive clinical and biological characterization of AML+13 to date, and reveals a striking clustering of lesions in a few genes, defining AML+13 as a genetically homogenous leukemia subgroup with alterations in a few critical cellular pathways. These studies were registered at clinicaltrials.gov, identifiers: AMLCG-1999: NCT00266136; AML96: NCT00180115; AML2003: NCT00180102; and AML60+: NCT00893373.
    Blood 06/2014; · 9.06 Impact Factor
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    ABSTRACT: In acute myeloid leukemia (AML), assessment of minimal residual disease (MRD) by flow cytometry (flow MRD) after induction and consolidation therapy has been shown to provide independent prognostic information. However, data on the value of earlier flow MRD assessment is lacking. Therefore, the value of flow MRD detection was determined during aplasia in 178 patients achieving complete remission after treatment according to AMLCG induction protocols. Flow MRD-positivity during aplasia predicted poor outcome (5-year relapse-free survival (RFS) 16% vs 43%, P<0.001) independently from age and cytogenetic risk group (hazard ratio for MRD-positivity 1.71; P=0.009). Importantly, the prognosis of patients without detectable MRD was not impacted by morphological blast count during aplasia nor by MRD status post-induction. Early flow MRD was also evaluated in the context of existing risk factors. Flow MRD was prognostic within the intermediate cytogenetic risk group (5-year RFS 15% vs. 37%, p=0.016) as well as for patients with normal karyotype and NPM1 mutations (5-year RFS 13% vs. 49%, P=0.02) or FLT3-ITD (3-year RFS rates 9% vs. 44%, P=0.016). Early flow MRD assessment can improve current risk stratification approaches by prediction of RFS in AML and might facilitate adaptation of post-remission therapy for patients at high risk of relapse.Leukemia accepted article preview online, 10 June 2014; doi:10.1038/leu.2014.186.
    Leukemia. 06/2014;
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    ABSTRACT: Monitoring of minimal residual disease represents an important diagnostic tool to identify patients with acute myeloid leukemia at high risk for relapse. In this study the prognostic potential of minimal residual disease monitoring by quantitative real-time PCR of NPM1 mutations of patients treated in the AMLCG trials 1999, 2004 and 2008 was investigated. Minimal residual disease monitoring was performed in 588 samples of 158 NPM1 mutation A, B and D positive patients at diagnosis, in aplasia, after induction therapy, after consolidation therapy, and during follow-up with a sensitivity of 10-6. 127 patients (80.4%) achieved complete remission after induction therapy and of these 56 patients (44.1%) relapsed. At each checkpoints, minimal residual disease cut-offs were calculated. After induction therapy a cut-off NPM1 mutation ratio of 0.01 revealed a high hazard ratio of 4.26 and the highest sensitivity of 76% for the prediction of relapse. This was reflected in a cumulative incidence of relapse after 2 years of 77.8% for cut-off positive patients versus 26.4% for cut-off negative patients, respectively. In the favorable subgroup according to European LeukemiaNet, the cut-off after induction therapy also separates the cohort into two prognostic groups with a cumulative incidence of relapse of 76% versus 6% after 2 years. Our data demonstrate that in addition to pre-therapeutic factors, the individual minimal residual disease course is an important prognostic factor and could be included into clinical trials for the guidance of postremission therapy. Trials were registered at www.clinicaltrials.gov (#NCT01382147, #NCT00266136) and at the European Leukemia Trial Registry (#LN_AMLINT2004_230).
    Haematologica 05/2014; · 5.94 Impact Factor
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    ABSTRACT: Cytogenetically normal (CN) acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. For the practicing clinician, it is difficult to summarize the prognostic information of the growing number of clinical and molecular markers. Our purpose was to develop a widely applicable prognostic model by combining well-established pretreatment patient and disease characteristics. Two prognostic indices for CN-AML (PINA), one regarding overall survival (OS; PINAOS) and the other regarding relapse-free survival (RFS; PINARFS), were derived from data of 572 patients with CN-AML treated within the AML Cooperative Group 99 study (www.aml-score.org. On the basis of age (median, 60 years; range, 17 to 85 years), performance status, WBC count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were classified into the following three risk groups according to PINAOS and PINARFS: 29% of all patients and 32% of 381 responding patients had low-risk disease (5-year OS, 74%; 5-year RFS, 55%); 56% of all patients and 39% of responding patients had intermediate-risk disease (5-year OS, 28%; 5-year RFS, 27%), and 15% of all patients and 29% of responding patients had high-risk disease (5-year OS, 3%; 5-year RFS, 5%), respectively. PINAOS and PINARFS stratified outcome within European LeukemiaNet genetic groups. Both indices were confirmed on independent data from Cancer and Leukemia Group B/Alliance trials. We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with CN-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of CN-AML.
    Journal of Clinical Oncology 04/2014; · 18.04 Impact Factor
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    ABSTRACT: ScopeIn previous studies, we could show that the B vitamin nicotinamide (NAM) enhanced antimicrobial activity of neutrophils. Here, we assessed the effects of NAM in two models of experimental colitis.Methods and ResultsColitis was induced in C57BL/6 mice either by oral infection with Citrobacter rodentium or by DSS (dextran sodium sulphate) administration, and animals were systemically treated with NAM. Ex vivo bacterial clearance was assessed in murine and human whole blood, as well as isolated human neutrophils. In C. rodentium-induced colitis, NAM treatment resulted in markedly decreased systemic bacterial invasion, histological damage and increased fecal clearance of C. rodentium by up to 600-fold. In contrast, NAM had no effect when administered to neutrophil-depleted mice. Ex vivo stimulation of isolated human neutrophils, as well as murine and human whole blood with NAM led to increased clearance of C. rodentium and enhanced expression of antimicrobial peptides in neutrophils. Moreover, NAM treatment significantly ameliorated the course of DSS colitis, as assessed by body weight, histological damage and myeloperoxidase activity.Conclusion Pharmacological application of NAM mediates beneficial effects in bacterial and chemically induced colitis. Future studies are needed to explore the clinical potential of NAM in the context of intestinal bacterial infections and human inflammatory bowel disease (IBD).
    Molecular Nutrition & Food Research 04/2014; · 4.31 Impact Factor
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    ABSTRACT: Acute myeloid leukaemia (AML) is a heterogenous disease. Prognosis of AML is influenced both by patient-specific as well as disease-specific factors. Age is the most prominent patient-specific risk factor, while chromosomal aberrations are the strongest disease-specific risk factors. For patients with cytogenetically normal AML, prognosis can be specified by mutational status of the genes NPM1, FLT3 and CEBPA. A growing number of recurrent mutations in additional genes have recently been identified, for which the prognostic effect yet has to be determined. Performance status, geriatric assessment, secondary leukaemia following myelodysplastic syndrome or cytotoxic treatment, common laboratory parameters, leukaemic stem cell frequency, bone marrow microenvironment, gene expression levels, epigenetic changes, micro-RNA's as well as kinetics and depth of response to treatment influence prognosis of AML patients. Despite the high number of established risk factors, only few predictive markers exist which can truly aid therapy decisions in patients with AML.
    British Journal of Haematology 02/2014; · 4.94 Impact Factor
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    ABSTRACT: External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.
    PLoS ONE 01/2014; 9(4):e94993. · 3.73 Impact Factor
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    ABSTRACT: About 30% of patients with acute myeloid leukemia (AML) harbour mutations of the receptor tyrosine kinase FLT3, mostly internal tandem duplications (ITD) and point mutations of the second tyrosine kinase domain (TKD). It was the aim of this study to comprehensively analyze clinical and functional properties of various FLT3 mutants. In 672 normal karyotype AML patients FLT3-ITD, but not FLT3-TKD mutations were associated with a worse relapse free and overall survival in multivariate analysis. In paired diagnosis-relapse samples FLT3-ITD showed higher stability (70%) compared to FLT3-TKD (30%). In vitro, FLT3-ITD induced a strong activating phenotype in Ba/F3 cells. In contrast, FLT3-TKD mutations and other point mutations - including two novel mutations - showed a weaker but clear gain-of-function phenotype with gradual increase in proliferation and protection from apoptosis. The pro-proliferative capacity of the investigated FLT3 mutants was associated with cell surface expression and tyrosine 591 phosphorylation of the FLT3 receptor. Western blot experiments revealed STAT5 activation only in FLT3-ITD positive cell lines, in contrast to FLT3-non-ITD mutants, which displayed an enhanced signal of AKT and MAPK activation. Gene expression analysis revealed distinct difference between FLT3-ITD and FLT3-TKD for STAT5 target gene expression as well as deregulation of SOCS2, ENPP2, PRUNE2 and ART3. FLT3-ITD and FLT3 point mutations show a gain-of-function phenotype with distinct signalling properties in vitro. Although poor prognosis in AML is only associated with FLT3-ITD, all activating FLT3 mutations can contribute to leukemogenesis and are thus potential targets for therapeutic interventions.
    PLoS ONE 01/2014; 9(3):e89560. · 3.73 Impact Factor
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    ABSTRACT: The majority of patients with acute myeloid leukemia (AML) who achieve complete remission (CR) relapse with conventional postremission chemotherapy. Allogeneic stem-cell transplantation (alloSCT) might improve survival at the expense of increased toxicity. It remains unknown for which patients alloSCT is preferable. We compared the outcome of 185 matched pairs of a large multicenter clinical trial (AMLCG99). Patients younger than 60 years who underwent alloSCT in first remission (CR1) were matched to patients who received conventional postremission therapy. The main matching criteria were AML type, cytogenetic risk group, patient age, and time in first CR. In the overall pairwise compared AML population, the projected 7-year overall survival (OS) rate was 58% for the alloSCT and 46% for the conventional postremission treatment group (P = .037; log-rank test). Relapse-free survival (RFS) was 52% in the alloSCT group compared with 33% in the control group (P < .001). OS was significantly better for alloSCT in patient subgroups with nonfavorable chromosomal aberrations, patients older than 45 years, and patients with secondary AML or high-risk myelodysplastic syndrome. For the entire patient cohort, postremission therapy was an independent factor for OS (hazard ratio, 0.66; 95% CI, 0.49 to 0.89 for alloSCT v conventional chemotherapy), among age, cytogenetics, and bone marrow blasts after the first induction cycle. AlloSCT is the most potent postremission therapy for AML and is particularly active for patients 45 to 59 years of age and/or those with high-risk cytogenetics.
    Journal of Clinical Oncology 12/2013; · 18.04 Impact Factor
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    ABSTRACT: Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. An in vivo selection approach was used to generate highly aggressive non-small cell lung cancer (NSCLC) cell lines (A549 and HTB56) followed by genome wide DNA methylation analysis. Furthermore, the therapeutic effects of the epigenetic agent Azacytidine on DNA methylation patterns and the in vivo phenotypes were explored. Widespread changes of DNA methylation were observed during development of highly aggressive cell lines. Up to 2.5% of the CpG rich region was differentially methylated as identified by Reduced Representation Bisulfite Sequencing (RRBS) compared to the less aggressive parental cell lines. DNA methyltransferase inhibition by Azacytidine reversed the pro-metastatic phenotype; this was highly associated with the preferential loss of DNA methylation at sites that were hypermethylated during the in vivo selection. Of note, polycomb (PRC2) binding sites were particularly affected by DNA methylation changes after Azacytidine exposure which persisted over time. We could show that metastatic capability of NSCLC is closely associated with DNA methylome alterations. Since inhibition of DNA methyltransferase reversed metastasis-prone phenotype, epigenetic modulation appears as a potential therapeutic approach to prevent metastasis formation.
    Clinical Cancer Research 12/2013; · 7.84 Impact Factor
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    ABSTRACT: Chemo-modulation of cytarabine by fludarabine has been attributed with a higher anti-leukemic efficacy, but randomized trials to address this question are rare. We therefore conducted a multicenter, randomized phase III study to evaluate the antileukemic efficacy of adding fludarabine to sequential high-dose cytarabine+idarubicin (SHAI) re-induction chemotherapy in relapsed or refractory acute myeloid leukemia (AML). Patients (n=326, 281 evaluable) were randomly assigned to SHAI (cytarabine 1 g/m(2) bid days 1-2 and 8-9 [3 g/m(2) for patients60 years with refractory AML or2nd relapse], idarubicin 10 mg/m(2) daily days 3-4 and 10-11) or F-SHAI (SHAI with fludarabine 15 mg/m(2) 4 hours prior to cytarabine). While complete remission (CR) rates (35% SHAI and 44% F-SHAI) and overall survival did not differ between both regimens, fludarabine prolonged time-to-treatment failure from 2.04 months to 3.38 months (median, P<0.05). Twenty-seven percent of patients proceeded to allogeneic SCT, with a significantly higher number of patients in CR or CRi in the F-SHAI group (22% versus 10%, P<0.01). In conclusion, fludarabine has a beneficial though moderate impact on the antileukemic efficacy of high-dose cytarabine based salvage therapy for relapsed and refractory AML.Leukemia accepted article preview online, 22 October 2013; doi:10.1038/leu.2013.297.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 10/2013; · 10.16 Impact Factor
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    ABSTRACT: The fusion protein tTF-NGR consists of the extracellular domain of the thrombogenic human tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA (NGR), a ligand of the surface protein CD13 (aminopeptidase N), upregulated on endothelial cells of tumor vessels. tTF-NGR preferentially activates blood coagulation within tumor vasculature, resulting in tumor vessel infarction and subsequent tumor growth retardation/regression. The anti-vascular mechanism of the tTF-NGR therapy approach was verified by quantifying the reduced tumor blood-perfusion with contrast-enhanced ultrasound, the reduced relative tumor blood volume by ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging, and by in vivo-evaluation of hemorrhagic bleeding with fluorescent biomarkers (AngioSense(680)) in fluorescence reflectance imaging. The accumulation of tTF-NGR within the tumor was proven by visualizing the distribution of the iodine-123-labelled protein by single-photon emission computed tomography. Use of these multi-modal vascular and molecular imaging tools helped to assess the therapeutic effect even at real time and to detect non-responding tumors directly after the first tTF-NGR treatment. This emphasizes the importance of imaging within clinical studies with tTF-NGR. The imaging techniques as used here have applicability within a wider scope of therapeutic regimes interfering with tumor vasculature. Some even are useful to obtain predictive biosignals in personalized cancer treatment.
    Angiogenesis 10/2013; · 3.97 Impact Factor
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    ABSTRACT: After undergoing allogeneic stem cell transplantation (alloSCT), patients adapt in very different ways to their taxing situation. Some patients cope very well; others almost seem to fail. Psychosocial variables are important factors for successful reintegration. Besides quality of life, resilience may help to understand the variance in individual differences in adaptation after alloSCT. A pilot study at the University Hospital Muenster, Germany, assessed resilience in patients after alloSCT. The sample included 75 patients (leukemia, lymphoma, myeloma, aplastic anemia) aged 20-76 years. The instruments Resilience Scale RS-25, Hospital Anxiety and Depression Scale, General Self-efficacy Scale, and EORTC QLQ-C30 were used. Resilience is positively correlated with quality of life (Spearman's rho 0.587) and social functioning (0.472), negatively with anxiety (-0.491) and depression (-0.577). Dividing the sample at the median resilience score of 144 reveals that high-resilience patients report less anxiety (p = 0.008) and depression (p < 0.001); higher physical (p = 0.041), emotional (p = 0.030), and social functioning (p = 0.003); and a better quality of life (p < 0.001) than low-resilience patients. No effects on resilience were found for age, gender, and primary disease entity. The high correlation of resilience and self-efficacy (r = 0.698) shows the strong relationship between the two concepts. Our results indicate a potential influence of the time span from alloSCT on patients' resilience. Resilience should be considered as a protective psychosocial factor for patients after alloSCT. A high degree of resilience can help patients to adapt to their situation and to resume their everyday life.
    Supportive Care in Cancer 10/2013; · 2.09 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2013; · 10.16 Impact Factor
  • Annals of Hematology 09/2013; · 2.87 Impact Factor
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    ABSTRACT: Acute myeloid leukemia (AML) is a rapidly progressing disease that is accompanied by a strong increase in microvessel density in the bone marrow. This observation prompted us to stain biopsies of AML and acute lymphoid leukemia (ALL) patients with the clinical-stage human monoclonal antibodies F8, L19, and F16 directed against markers of tumor angiogenesis. The analysis revealed that the F8 and F16 antibodies strongly stained 70% of AML and 75% of ALL bone marrow specimens, whereas chloroma biopsies were stained with all three antibodies. Therapy experiments performed in immunocompromised mice bearing human NB4 leukemia with the immunocytokine F8-IL2 [consisting of the F8 antibody fused to human interleukin-2 (IL-2)] mediated a strong inhibition of AML progression. This effect was potentiated by the addition of cytarabine, promoting complete responses in 40% of treated animals. Experiments performed in immunocompetent mice bearing C1498 murine leukemia revealed long-lasting complete tumor eradication in all treated mice. The therapeutic effect of F8-IL2 was mediated by both natural killer cells and CD8(+) T cells, whereas CD4(+) T cells appeared to be dispensable, as determined in immunodepletion experiments. The treatment of an AML patient with disseminated extramedullary AML manifestations with F16-IL2 (consisting of the F16 antibody fused to human IL-2, currently being tested in phase 2 clinical trials in patients with solid tumors) and low-dose cytarabine showed significant reduction of AML lesions and underlines the translational potential of vascular tumor-targeting antibody-cytokine fusions for the treatment of patients with leukemia.
    Science translational medicine 09/2013; 5(201):201ra118. · 10.76 Impact Factor
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    T Schoofs, W E Berdel, C Müller-Tidow
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    ABSTRACT: Aberrant DNA methylation patterns are a characteristic feature of cancer including myeloid malignancies such as acute myeloid leukemia (AML). The mechanisms behind aberrant DNA methylation have long remained obscure. New genome-wide studies have elucidated the genome and epigenome of solid tumors and AML. Molecular subtypes of AML were found to exhibit highly distinct DNA methylation profiles. Clonal evolution patterns of AML were recently dissected and might shape epigenetic dysregulation. Also, recurrent mutations in epigenetic modifying enzymes were identified in AML and linked to distinct DNA methylation signatures. The genetic background, thus, takes center stage as a driver of epigenetic dysregulation in AML. First mechanistic insights into the dysregulation of DNA methylation by recurrent mutations have already been gained. Other studies suggest that epigenomic plasticity and aging-associated changes in DNA methylation also contribute extensively to aberrant DNA methylation in cancer. Epigenetic dysregulation, therefore, seems to also occur independently of the genetic background. Furthermore, global changes in chromatin conformation and nuclear organization have also been proposed as potential contributors to aberrant DNA methylation. This review will summarize and discuss current concepts regarding the mechanisms behind aberrant DNA methylation in cancer and specifically AML.Leukemia accepted article preview online, 20 August 2013. doi:10.1038/leu.2013.242.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2013; · 10.16 Impact Factor
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    ABSTRACT: Polo-like kinases (Plks) play an important role in cell cycle checkpoint controls and are over-expressed in acute myeloid leukaemia (AML). BI 2536, a novel Plk inhibitor, induces mitotic arrest and apoptosis. In this phase I/II trial of BI 2536 in 68 elderly patients with relapsed/refractory AML, three schedules were investigated (day 1, days 1-3, and days 1 + 8). Maximum tolerated dose was 350 and 200 mg in the day 1 and days 1 + 8 schedules, respectively. The day 1-3 schedule appeared equivalent to the day 1 schedule and was discontinued early. BI 2536 exhibited multi-compartmental pharmacokinetic behaviour. The majority of patients showed an increase of bone marrow cells in G2/M with a characteristic pattern of mitotic catastrophe. The overall response rate in the day 1 and day 1 + 8 schedules was 9% (5/54) with 2 complete and 3 partial responses. The majority of drug-related adverse events grade ≥3 were haematological. Taken together, Plk inhibition induced cell cycle arrest in AML blasts in vivo and BI 2536 monotherapy showed modest clinical activity in this poor prognosis patient group.
    British Journal of Haematology 08/2013; · 4.94 Impact Factor
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    ABSTRACT: PURPOSEThe prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML. PATIENTS AND METHODS All patients received standard cytarabine and daunorubicin induction (7+3 regimen) and up to two cycles of intermediate-dose cytarabine consolidation. Two hundred one patients were equally randomly assigned to receive either sorafenib or placebo between the chemotherapy cycles and subsequently for up to 1 year after the beginning of therapy. The primary objective was to test for an improvement in event-free survival (EFS). Overall survival (OS), complete remission (CR) rate, tolerability, and several predefined subgroup analyses were among the secondary objectives.ResultsAge, sex, CR and early death (ED) probability, and prognostic factors were balanced between both study arms. Treatment in the sorafenib arm did not result in significant improvement in EFS or OS. This was also true for subgroup analyses, including the subgroup positive for FLT3 internal tandem duplications. Results of induction therapy were worse in the sorafenib arm, with higher treatment-related mortality and lower CR rates. More adverse effects occurred during induction therapy in the sorafenib arm, and patients in this arm received less consolidation chemotherapy as a result of higher induction toxicity.DiscussionIn conclusion, combination of standard induction and consolidation therapy with sorafenib in the schedule investigated in our trial is not beneficial for elderly patients with AML.
    Journal of Clinical Oncology 07/2013; · 18.04 Impact Factor

Publication Stats

10k Citations
2,736.81 Total Impact Points

Institutions

  • 1999–2014
    • University of Münster
      • • Faculty of Medicine
      • • Department of Medicine, Hematology and Oncology
      Muenster, North Rhine-Westphalia, Germany
  • 2003–2012
    • Ludwig-Maximilian-University of Munich
      • Department of Internal Medicine II
      München, Bavaria, Germany
  • 2001–2012
    • Universitätsklinikum Münster
      • • Medizinische Klinik B
      • • Institut für Humangenetik
      • • Medizinische Klinik und Poliklinik A
      Muenster, North Rhine-Westphalia, Germany
  • 2011
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany
  • 2003–2009
    • University of Hamburg
      • • Department of Stem Cell Transplantation
      • • Center for Oncology
      Hamburg, Hamburg, Germany
  • 2008
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 2007
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2006
    • Charité Universitätsmedizin Berlin
      • Department of Pediatrics, Division of Oncology and Hematology
      Berlín, Berlin, Germany
  • 2005
    • Jiangsu University
      • Institute of Life Sciences
      Zhenjiang, Jiangsu Sheng, China
    • Bundeswehrzentralkrankenhaus Koblenz
      Coblenz, Rheinland-Pfalz, Germany
  • 2004
    • University Medical Center Hamburg - Eppendorf
      Hamburg, Hamburg, Germany
  • 2000–2001
    • Cedars-Sinai Medical Center
      • Division of Hematology and Oncology
      Los Angeles, CA, United States
    • California Institute of Technology
      • Division of Biology
      Pasadena, California, United States
  • 1997–1998
    • Max-Delbrück-Centrum für Molekulare Medizin
      Berlín, Berlin, Germany
  • 1991–1998
    • Freie Universität Berlin
      • Department of Hematology
      Berlín, Berlin, Germany
  • 1988–1994
    • Emory University
      • • Department of Hematology and Medical Oncology
      • • Department of Internal Medicine
      • • School of Medicine
      Atlanta, GA, United States
  • 1981–1993
    • Technische Universität München
      • Medizinische Klinik und Poliklinik I
      München, Bavaria, Germany
  • 1992
    • Roswell Park Cancer Institute
      • Department of Neurosurgery
      Buffalo, New York, United States
  • 1981–1990
    • Deutsches Herzzentrum München
      München, Bavaria, Germany
  • 1986
    • University of Texas Health Science Center at San Antonio
      • Division of Hospital Medicine
      San Antonio, Texas, United States