Wolfgang E Berdel

Universitätsklinikum Münster, Muenster, North Rhine-Westphalia, Germany

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Publications (548)2972 Total impact

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    ABSTRACT: We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML-Study IV, a randomized five-arm trial designed to optimize imatinib therapy were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI). 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were: CCI 2: n=589, CCI 3 or 4: n=599, CCI 5 or 6: n=229, and CCI ≥ 7: n=102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4%, for patients with CCI 2, 3-4, 5-6 and ≥ 7. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as outcome measure for specific CML treatments. Copyright © 2015 American Society of Hematology.
    Blood 04/2015; DOI:10.1182/blood-2015-01-617993 · 9.78 Impact Factor
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    ABSTRACT: Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cancer cell 04/2015; 27(5). DOI:10.1016/j.ccell.2015.03.017 · 23.89 Impact Factor
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    ABSTRACT: There is increasing interest in the site-directed pharmacodelivery of therapeutic payloads to the tumor site using antibodies as transport vehicles. Here, we investigated the efficacy of L19-IL2, an antibody-cytokine fusion protein that specifically delivers IL-2 to the tumor site by homing to the extra-domain B of fibronectin (EDB-Fn) expressed on tumor-associated blood vessels, against mantle cell lymphoma (MCL) in mice. L19-IL2 was shown to selectively localize at lymphoma lesions in vivo and to mediate significant lymphoma growth retardation, which was potentiated by co-administration of the anti-CD20 antibody rituximab. When co-injected with rituximab, L19-IL2 induced complete remissions of localized MCL xenografts in 6/8 mice (75%), whereas the combination of rituximab and equivalent doses of non-targeted IL-2 only slightly delayed tumor growth. In disseminated MCL, combination therapy with L19-IL2 and rituximab exhibited a significant survival benefit over treatment with IL-2 and rituximab and completely eradicated the disease in 2/7 cases (28.6%). Mechanistically, histological analyses of post-therapeutic lymphoma tissues revealed a strong intratumoral accumulation of macrophages and natural killer cells after a single dose of the immunocytokine, whereas L19-IL2 had no significant impact on microvessel density or on tissue penetration of co-injected rituximab. Collectively, these results provide the scientific rationale for the clinical evaluation of L19-IL2 in combination with anti-CD20 immunotherapy in patients with MCL. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Leukemia research 04/2015; DOI:10.1016/j.leukres.2015.04.005 · 2.69 Impact Factor
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    ABSTRACT: Perioperative chemotherapy increases the overall and progression-free survival of patients suffering from resectable adenocarcinomas of the lower esophagus, gastroesophageal junction and stomach (GEC). Comparing different chemotherapy regimens platin-based protocols with 5-fluorouracil (5-FU)/calcium folinate (CF) or oral fluoropyrimidines were favorable in terms of efficacy and side-effects. However, there is no consensus which regimen is the most efficacious. 42 consecutive patients with resectable GEC (UICC II and III) were treated with 3 pre- and postoperative chemotherapy cycles each consisting of epirubicin, oxaliplatin and capecitabine (EOX). We analyzed the overall survival, progression-free survival and toxicity retrospectively in comparison to published data. The median overall survival in our cohort was 29 months and the progression-free survival was 17 months. The most frequent grade 3 and 4 toxicities during preoperative chemotherapy were diarrhea (16.7%), leukocytopenia (9.5%) and nausea (9.5%); overall 38.1% of our patients suffered from grade 3 or 4 toxicity. Surgery was carried out in 83% of our patients, 69% of those achieved R0 resection. Comparing our data with the results of previously published randomized trials EOX is at least non-inferior with regard to overall survival, progression-free survival and toxicity. In conclusion, EOX is an appropriate perioperative therapy for patients with resectable GEC.
    PLoS ONE 04/2015; 10(4):e0122974. DOI:10.1371/journal.pone.0122974 · 3.53 Impact Factor
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    ABSTRACT: Dear Editor,Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder characterized by hypercytokinemia, undulating signs of systemic inflammation, generalized lymphadenopathy, hepatosplenomegaly, and in severe cases vascular leak syndrome (VLS), organ failure, and death [1]. It is categorized into HHV8-positive MCD (HMCD), including HIV patients, and idiopathic MCD (iMCD). Therapeutic monoclonal antibodies are the mainstay of treatment. Whereas the anti-CD20 antibody rituximab is preferentially advocated for HMCD [2, 3], the IL-6 disrupting antibodies tocilizumab and siltuximab are for iMCD [4]. We report the first case, to our knowledge, of a patient with severe iMCD responding with repeated long-lasting complete remissions (CR) to rituximab monotherapy and after failure a complete remission to allogeneic stem cell transplantation (alloSCT).In July 2008, a 25-year-old man was admitted to our intensive care unit with fever of unknown origin, acute renal failure, an ...
    Annals of Hematology 03/2015; 94(7). DOI:10.1007/s00277-015-2353-8 · 2.40 Impact Factor
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    ABSTRACT: The antibody-based delivery of interleukin-2 (IL-2) to extracellular targets expressed in the easily accessible tumor-associated vasculature has shown potent anti-leukemic activity in xenograft and immunocompetent murine models of acute myeloid leukemia (AML), especially in combination with cytarabine. Here, we report our experiences in four patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, in combination with low-dose cytarabine (LDAC). One patient with disseminated extramedullary AML lesions achieved a complete metabolic response in PET/CT, which lasted three months. Two out of three patients with bone marrow (BM) relapse achieved a blast reduction with transient molecular negativity. One of the two enjoyed a short complete remission before AML relapse occurred two months after the first infusion of F16-IL2. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells in the BM. Grade 2 fevers were the only non-hematological side effects in two patients. Grade 3 cytokine-release syndrome developed in the other two patients, but was manageable in both cases with glucocorticoids. The concept of specifically targeting IL-2 to the leukemia-associated stroma deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT. Copyright © 2015, American Association for Cancer Research.
    02/2015; 3(5). DOI:10.1158/2326-6066.CIR-14-0179
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    ABSTRACT: Epigenomic changes are an important feature of malignant tumors. How tumor aggressiveness is affected by DNA methylation of specific loci is largely unexplored. In genome wide DNA methylation analyses we identified the KCa 3.1 channel gene (KCNN4) promoter to be hypomethylated in an aggressive non-small cell lung carcinoma (NSCLC) cell line and in patient samples. Accordingly, KCa 3.1 expression was increased in more aggressive NSCLC cells. Both findings were strong predictors for poor prognosis in lung adenocarcinoma. Increased KCa 3.1 expression was associated with aggressive features of NSCLC cells. Proliferation and migration of pro-metastatic NSCLC cells depended on KCa 3.1 activity. Mechanistically, elevated KCa 3.1 expression hyperpolarized the membrane potential thereby augmenting the driving force for Ca(2+) influx. KCa 3.1 blockade strongly reduced the growth of xenografted NSCLC cells in mice as measured by PET-CT. Thus, loss of DNA methylation of the KCNN4 promoter and increased KCa 3.1 channel expression and function are mechanistically linked to poor survival of NSCLC patients. This article is protected by copyright. All rights reserved. Copyright © 2015 UICC.
    International Journal of Cancer 02/2015; DOI:10.1002/ijc.29490 · 5.01 Impact Factor
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    ABSTRACT: Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.Bone Marrow Transplantation advance online publication, 19 January 2015; doi:10.1038/bmt.2014.300.
    Bone Marrow Transplantation 01/2015; DOI:10.1038/bmt.2014.300 · 3.47 Impact Factor
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    ABSTRACT: Purpose:KRAS mutations are frequent driver mutations in multiple cancers. KRAS mutations also induce anti-EGFR antibody resistance in adenocarcinoma such as colon cancer. The aim of this study was to overcome anti-EGFR antibody resistance by coupling the antibody to KRAS-specific siRNA. Experimental Design:The anti-EGFR antibody was chemically coupled to siRNA. The resulting complex was tested for antibody binding efficiency, serum stability and ability to deliver siRNA to EGFR expressing cells. Western blotting, viability, apoptosis and colony formation assays were performed for efficacy evaluation in vitro. Furthermore, therapeutic activity of the antibody-KRAS-siRNA complexes was examined in in vivo xenograft mouse tumor models. Results:Antibody-siRNA complexes were targeted and internalized via the EGFR receptor. Upon internalization, target gene expression was strongly and specifically repressed, followed by a reduced proliferation and viability, and induced apoptosis of the cells in vitro. Clonogenic growth of mutant KRAS bearing cells was suppressed by KRAS-siRNA-anti-EGFR antibody complexes. In xenograft mouse models, anti-EGFR antibody-KRAS-siRNA complexes significantly slowed tumor growth in anti-EGFR resistant cells. Conclusions:The coupling of siRNA against KRAS to anti-EGFR antibodies provides a novel therapy approach for KRAS-mutated EGFR-positive cancer cells in vitro and in vivo. These findings provide an innovative approach for cancer specific siRNA application and for enhanced therapeutic potential of monoclonal antibody therapy and personalized treatment of cancer entities. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 01/2015; 21(6). DOI:10.1158/1078-0432.CCR-13-2017 · 8.19 Impact Factor
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    ABSTRACT: Multiplex PCR (mPCR) directly from blood has been suggested as a promising method for rapid identification of pathogens causing sepsis. This study aimed to investigate whether mPCR has any impact on antimicrobial treatment. Hematological patients with febrile neutropenia were randomized into two groups. In the study group, mPCR was performed as an addition to standard diagnostics, and PCR finding was immediately communicated to the clinicians, thus being available for decision making. In the control group, clinicians were not aware of PCR result. PCR samples were collected simultaneously with clinically indicated blood culture specimens from peripheral vein and/or central venous catheter at fever onset and once again if fever persisted up to 72 h. Overall, 74 patients of the study group and 76 patients of the control group were enrolled and 253 samples collected. Therapy was changed to targeted antimicrobial therapy (AMT) in 12 patients (16.2 %) in the study group and in 12 patients (15.8 %) in the control group. For patients with changes, the median time to change to the targeted AMT was 21.4 h in the study group and 47.5 h in the control group (p = 0.018). In the study group, 57.1 % (8/14) of changes to targeted AMT was due to PCR finding. PCR led to AMT change in 9.5 % (7/74) of study group patients, i.e., in 33.3 % (7/21) of patients who had positive PCR finding. There were no significant differences in patient outcomes (secondary endpoints). In conclusion, PCR method accelerates change to the targeted AMT in febrile neutropenic patients.
    Medical Microbiology and Immunology 01/2015; DOI:10.1007/s00430-014-0385-7 · 2.43 Impact Factor
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    ABSTRACT: The presence of a mutated nucleophosmin-1 gene (NPM1mut) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1mut AML eligible for allogeneic SCT in a donor versus no-donor analysis. Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1mut patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor. Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300). Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1mut AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1mut patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1mut AML with a sibling donor. © 2014 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 12/2014; 33(5). DOI:10.1200/JCO.2013.54.4973 · 17.88 Impact Factor
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    ABSTRACT: Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1-/- bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1-/- in MLL-AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia.
    PLoS ONE 12/2014; 9(12):e115578. DOI:10.1371/journal.pone.0115578 · 3.53 Impact Factor
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    ABSTRACT: The DNA methyltransferase (DNMT) inhibitory drugs such as 5-azacytidine induce DNA hypomethylation by inhibiting DNA methyltransferases. While clinically effective, DNMT inhibitors are not curative. A combination with cytotoxic drugs might be beneficial, but this is largely unexplored. In the present study, we analyzed potential synergisms between cytotoxic drugs and 5-azacytidine in acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC) cells. Lung cancer and leukemia cell lines were exposed to low doses of 5-azacytidine with varying doses of cytarabine or etoposide for AML cells (U937 and HL60) as well as cisplatin or gemcitabine for NSCLC cells (A549 and HTB56) for 48 h. Drug interaction and potential synergism was analyzed according to the Chou-Talalay algorithm. Further analyses were based on soft agar colony formation assays, active caspase-3 staining and BrdU incorporation flow cytometry. To identify effects on DNA methylation patterns, we performed genome wide DNA methylation analysis using 450K bead arrays. Azacytidine at low doses was synergistic with cytotoxic drugs in NSCLC and in AML cell lines. Simultaneous exposure to 5-azacytidine with cytotoxic drugs showed strong synergistic activity. In colony formation assays these synergisms were repeatedly verified for 5-azacytidine (25 nM) with low doses of anticancer agents. 5-azacytidine neither affected the cell cycle nor increased apoptosis. 450K methylation bead arrays revealed 1,046 CpG sites in AML and 1,778 CpG sites in NSCLC cells with significant DNA hypomethylation (24-h exposure) to 5-azacytidine combined with the cytotoxic drugs. These CpG-sites were observed in the candidate tumor-suppressor genes MGMT and THRB. Additional incubation time after 24-h treatment led to a 4.1-fold increase of significant hypomethylated CpG-sites in NSCLC cells. These results suggest that the addition of DNA demethylating agents to cytotoxic anticancer drugs exhibits synergistic activity in AML and NSCLC. Dysregulation of an equilibrium of DNA methylation in cancer cells might increase the susceptibility for cytotoxic drugs.
    International Journal of Oncology 12/2014; 46(3). DOI:10.3892/ijo.2014.2792 · 2.77 Impact Factor
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    ABSTRACT: The inhibition of serum glucocorticoid-regulated kinase-1 (SGK-1) has been found to decrease growth of colon and prostate cancer cells. The purpose of this study is to evaluate the therapeutic effect of SGK-1 inhibition in head and neck squamous cell carcinoma (SCC). Human head and neck tumors (HTB41/43) were established in athymic mice. Growth rates between mice treated with vehicle (PBS) injection (group 1, n = 5), SGK-1 Inhibitor GSK 650394 (group 2, n = 6), systemic cisplatin (group 3, n = 6), and a combination of SGK-1 Inhibitor and cisplatin (group 4, n = 6) were compared using repeated measures one-way ANOVA with Newman-Keuls Multiple Comparison Test. Tumor cells were subsequently submitted to further analyses. At the end of the experiment mean tumor sizes were 122.33+/-105.86, 76.73+/-36.09, 94.52+/-75.92, and 25.76+/-14.89 mm2 (mean +/- SD) for groups 1 to 4. Groups 2 and 3 showed decreased tumor growth compared to controls (p<0.001). Group 4 displayed even greater growth suppression (p<0.0001). Importantly, group 4 fared better than group 3 (p<0.001). CD44 expression was reduced in group 2 (p<0.05), and to an even greater extent in groups 3 and 4 (p<0.0025). A trend towards reduction of HER 2 expression was noted in group 4. SGK-1 inhibition suppresses tumor growth, and in combination with systemic cisplatin exceeds the effect of cisplatin alone. Decreased expression of CD44 and HER 2 implies depletion of tumor stem cells, and less tumorigenicity. SGK-1 inhibition represents a potential modality of local control for palliation in advanced cases.
    PLoS ONE 12/2014; 9(12):e113795. DOI:10.1371/journal.pone.0113795 · 3.53 Impact Factor
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    ABSTRACT: The optimal timing of allogeneic hematopoietic transplantation (HCT) in AML is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in the first remission was offered also to patients with an FLT3-ITD allelic ratio >0.8, poor day +15 marrow blast clearance, and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy.Leukemia accepted article preview online, 01 December 2014. doi:10.1038/leu.2014.335.
    Leukemia 12/2014; 29(5). DOI:10.1038/leu.2014.335 · 9.38 Impact Factor
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    ABSTRACT: Recurrent respiratory papillomatosis (RRP) is a primary benign disease, which is characterized by papillomatous growth in the respiratory tract. Malignant transformation occurs in only 3-5% of cases, however, local growth of the benign papillomas is interpreted as clinically malignant in a markedly higher proportion of patients. Local surgical or endoscopic interventional debulking or excision is currently the commonly selected treatment method and antiviral therapy is a potential adjuvant approach. However, the long-term management of RRP patients, who commonly require multiple procedures over numerous years, is challenging and the overall therapeutic armamentarium remains unsatisfactory. The administration of systemic bevacizumab treatment in a series of five patients with long histories of RRP, who required repeated local interventions to control papilloma growth is evaluated. Treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was administered at a dose of 5 mg/kg (n=1), 10 mg/kg (n=3) or 15 mg/kg (n=1) intravenously to the five RRP patients, who were clinically classified as exhibiting progressive disease. Endoscopic evaluations were performed prior to the first infusion of bevacizumab and intermittently at variable time points during the course of therapy. Histopathological analyses were performed using pre- and post-treatment papilloma biopsies, including immunohistochemical analyses of VEGF and phosphorylated VEGF receptor (VEGFR)-2 expression. The patients received between three and 16 courses of bevacizumab (median, six courses). The first course was initiated when progression following the previous intervention was observed. An immediate response to bevacizumab treatment was demonstrated in all five RRP patients. While the cumulative number of interventions in the five patients was 18 throughout the 12 months prior to the initiation of bevacizumab treatment, only one patient required interventional treatment due to a malignant transformation during the 12 months following treatment with bevacizumab (18 vs. 1 interventions, P=0.042). Histopathological analyses revealed regressive perivascular edema and normalization of the vascular structure, however, immunohistochemical analyses of the VEGF and phosphorylated VEGFR-2 expression did not demonstrate any changes following therapy. Due to the limited number of alternative treatments, VEGF-targeted therapies may represent a promising novel strategy in the treatment of RRP, which may have the potential to modify the current treatment standards, particularly in patients with poorly accessible papilloma lesions, however, this requires further investigation in clinical trials.
    Oncology letters 11/2014; 8(5):1912-1918. DOI:10.3892/ol.2014.2486 · 0.99 Impact Factor
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    ABSTRACT: NPM1 mutations represent frequent genetic alterations in patients with acute myeloid leukemia (AML) associated with a favorable prognosis. Different types of NPM1 mutations have been described. The purpose of our study was to evaluate the relevance of different NPM1 mutation types with regard to clinical outcome. Our analyses were based on 349 NPM1-mutated AML patients treated in the AMLCG99 trial. Complete remission rates, overall survival and relapse-free survival were not significantly different between patients with NPM1 type A or rare type mutations. The NPM1 mutation type does not seem to play a role in risk stratification of cytogenetically normal AML.
    PLoS ONE 10/2014; 9(10):e109759. DOI:10.1371/journal.pone.0109759 · 3.53 Impact Factor
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    ABSTRACT: Background The aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations.Patients and methodsWe investigated 88 AML patients with a median age of 61 years and (1) cytogenetically normal AML (CN-AML), (2) monoallelic (moCEBPA) or biallelic (biCEBPA) CEBPA mutation, and (3) intensive induction treatment. 60/88 patients have been described previously with a shorter follow-up.ResultsMedian follow-up time was 9.8 years (95% CI: 9.4-10.1 years) compared to 3.2 and 5.2 years in our former analyses. Patients with biCEBPA survived significantly longer compared to those with moCEBPA (median overall survival (OS) 9.6 years vs. 1.7 years, p¿=¿0.008). Patients¿¿¿60 years and biCEBPA mutations showed a favorable prognosis with a 10-year OS rate of 81%.Both, bi- and moCEBPA-mutated groups had a low early death (d60) rate of 7% and 9%, respectively. Complete remission (CR) rates for biCEBPA- and moCEBPA-mutated patients were 82% vs. 70% (p¿=¿0.17). biCEBPA-mutated patients showed a longer relapse free survival (RFS) (median RFS 9.4 years vs. 1.5 years, p¿=¿0.021) and a lower cumulative incidence of relapse (CIR) compared to moCEBPA-mutated patients. These differences in OS and RFS were confirmed after adjustment for known clinical and molecular prognostic factors.Conclusions In this long-term observation we confirmed the favorable prognostic outcome of patients with biCEBPA mutations compared to moCEBPA-mutated CN-AML. The high probability of OS (81%) in younger patients is helpful to guide intensity of postremission therapy.
    Journal of Hematology & Oncology 09/2014; 7(1):55. DOI:10.1186/s13045-014-0055-7 · 4.93 Impact Factor
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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; DOI:10.1097/JTO.0000000000000243 · 5.80 Impact Factor

Publication Stats

13k Citations
2,972.00 Total Impact Points


  • 2001–2015
    • Universitätsklinikum Münster
      • • Medizinische Klinik B
      • • Medizinische Klinik und Poliklinik A
      • • Institut für Humangenetik
      Muenster, North Rhine-Westphalia, Germany
  • 1999–2015
    • University of Münster
      • Department of Medicine, Hematology and Oncology
      Muenster, North Rhine-Westphalia, Germany
    • Sankt Elisabeth Hospital
      Bielefeld, North Rhine-Westphalia, Germany
  • 2003–2012
    • Ludwig-Maximilian-University of Munich
      • Department of Internal Medicine II
      München, Bavaria, Germany
  • 2010
    • Münchner Leukämie Labor GmbH
      München, Bavaria, Germany
  • 2004–2009
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
  • 2008
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 2007
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
    • Boehringer Ingelheim
      Ingelheim-Mitte, Rheinland-Pfalz, Germany
  • 2006
    • Charité Universitätsmedizin Berlin
      • Department of Pediatrics, Division of Oncology and Hematology
      Berlín, Berlin, Germany
  • 2005
    • Bundeswehrzentralkrankenhaus Koblenz
      Coblenz, Rheinland-Pfalz, Germany
  • 2001–2004
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 2002
    • University of Greifswald
      Griefswald, Mecklenburg-Vorpommern, Germany
    • Roswell Park Cancer Institute
      • Department of Neurosurgery
      Buffalo, New York, United States
  • 2000
    • California Institute of Technology
      • Division of Biology
      Pasadena, California, United States
  • 1991–1999
    • Freie Universität Berlin
      • Department of Hematology
      Berlín, Berlin, Germany
  • 1998
    • Max-Delbrück-Centrum für Molekulare Medizin
      Berlín, Berlin, Germany
  • 1988–1994
    • Emory University
      • • Department of Hematology and Medical Oncology
      • • School of Medicine
      Atlanta, GA, United States
  • 1993
    • University Hospital München
      München, Bavaria, Germany
  • 1981–1993
    • Technische Universität München
      • • Medizinische Klinik und Poliklinik I
      • • Abteilung für Hepatologie
      München, Bavaria, Germany
  • 1981–1990
    • Deutsches Herzzentrum München
      München, Bavaria, Germany
  • 1986
    • Umeå University
      Umeå, Västerbotten, Sweden