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Nürnberg, Germany

Middeke J.M.,TU Dresden | Herold S.,TU Dresden | Herold S.,German Cancer Research Center | Rucker-Braun E.,TU Dresden | And 23 more authors.
British Journal of Haematology | Year: 2016

Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse-risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three-year probabilities of overall survival (OS) and event-free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53-mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML. © 2016 John Wiley & Sons Ltd.


Saussele S.,University of Heidelberg | Lauseker M.,Ludwig Maximilians University of Munich | Gratwohl A.,University of Basel | Beelen D.W.,University of Duisburg - Essen | And 22 more authors.
Blood | Year: 2010

The role of allogeneic stem cell transplantation in chronic myeloid leukemia is being reevaluated. Whereas drug treatment has been shown to be superior in first-line treatment, data on allogeneic hematopoietic stem cell transplantation (allo SCT) as second-line therapy after imatinib failure are scarce. Using an interim safety analysis of the randomized German CML Study IV designed to optimize imatinib therapy by combination, dose escalation, and transplantation, we here report on 84 patients who underwent consecutive transplantation according to predefined criteria (low European Group for Blood and Marrow Transplantation [EBMT] score, imatinib failure, and advanced disease). Three-year survival after transplantation of 56 patients in chronic phase was 91% (median follow-up: 30 months). Transplantation-related mortality was 8%. In a matched pair comparison of patients who received a transplant and those who did not, survival was not different. Three-year survival after transplantation of 28 patients in advanced phase was 59%. Eighty-eight percent of patients who received a transplant achieved complete molecular remissions. We conclude that allo SCT could become the preferred second-line option after imatinib failure for suitable patients with a donor. The study is registered at the National Institutes of Health, http://clinicaltrials.gov:NCT00055874. © 2010 by The American Society of Hematology.


Schildberg C.W.,Friedrich - Alexander - University, Erlangen - Nuremberg | Abba M.,University of Heidelberg | Merkel S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Agaimy A.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 6 more authors.
Advances in Medical Sciences | Year: 2014

Purpose There is an increasing need to identify molecular markers, which can be used to prognosticate patient populations in gastric cancer. Whereas a significant number have been identified, very few have been characterized in the context of their ability to discriminate between young and old age groups in which a survival difference clearly exists. Material/methods In this study, using immunohistochemistry, we evaluated three markers with proven involvement in gastric cancer. The p53 tumor suppressor, the cell adhesion glycoprotein epithelial cadherin (CDH1) and the caudal-related homeobox transcription factor (CDX2) all of these have important roles in the aetiopathogenesis and/or progression of gastric cancer. Results After adjustments for TNM stage, tumor grade, histopathological characteristics (Lauren classification), we found significant differences in the expression of these proteins, particularly E-cadherin and CDX2 between young and elderly patients. However, these differences did not amount to a significant difference in survival. Conclusions This study demonstrates that the protein expression of p53, CDH1 and CDX2 significantly discriminates young patients with gastric cancer who have a better prognostic outlook from older patients, but this difference in expression does not contribute to a survival benefit. © 2014 Medical University of Bialystok.


Schildberg C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Abbas M.,University of Heidelberg | Merkel S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Agaimy A.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 6 more authors.
Journal of Surgical Oncology | Year: 2013

Background and Objectives Despite its dwindling occurrence, gastric cancer remains a leading cause of cancer related mortality worldwide. Molecular determinants of prognosis that impact survival are being sought out as a means to facilitate rational clinical decision-making and enhance patient management. In this study, we evaluated three molecules implicated in gastric carcinogenesis and demonstrated that the differential expression of cyclooxygenase-2 (COX-2) and the viral oncogene homolog Src proteins could explain the differences in survival observed in patients older and younger than 50 years of age. Methods We evaluated 5-year survival in a cohort of 423 gastric cancer patients using chronological age as a variable. Additionally, we assessed the protein expression of three molecules (COX-2, TFF1, Src) implicated in the pathogenesis of gastric cancer using immunohistochemistry. Results We found that patients younger than 50 years of age had a better 5-year survival rate in all tumor stages. We found that the expression of COX-2 and Src correlated significantly with survival in this group without any significant impact attributable to TFF1. Conclusions Our study demonstrates that young gastric cancer patients have a better prognostic outlook that could in part be explained by the differential expression of COX-2 and Src. J. Surg. Oncol. 2013; 108:409-413. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.


Von Weikersthal L.F.,Klinikum Sankt Marien | Schalhorn A.,Ludwig Maximilians University of Munich | Stauch M.,Oncological Practice | Maubach P.A.,Oncological Practice Nussbaumstrasse | And 10 more authors.
European Journal of Cancer | Year: 2011

Purpose: To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional 5-fluorouracil, leucovorin (FUFIRI) as first-line therapy of patients with metastatic colorectal cancer (mCRC). Patients and methods: A phase III, randomised, open-label multicentre study compared standard treatment with FUFIRI (irinotecan 80 mg/m2, 5-fluorouracil 2000 mg/m2, folinic acid 500 mg/m2 weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m2 applied on days 1, 15 and 29 of a 7-week cycle. The primary end-point was progression-free survival (PFS). Results: A total of 479 eligible patients were randomly assigned. Progression-free survival was 7.2 months in the mIROX arm and 8.2 months in the FUFIRI arm [hazard ratio = 1.14; 95% confidence interval (CI) 0.94-1.37; P = 0.178]. Comparable results were also obtained for overall survival time with 19 months in the mIROX-arm and 22 months in the FUFIRI-arm (hazard ratio = 1.08, P = 0.276). Both regimens induced an identical objective response rate (ORR) of 41%, but disease control rate (ORR plus stable disease) was significantly greater in the FUFIRI group (81% versus 68%, P = 0.001). Most frequent grades 1-4 side-effects of mIROX and FUFIRI treatment were nausea (80% versus 73%) and delayed diarrhoea (79% versus 68%). Grades 3-4 toxicities were generally below 10%, except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm (19% versus 30%, P = 0.006) Conclusion: mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan. Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a standard of care in first-line treatment of metastatic colorectal cancer. © 2010 Elsevier Ltd. All rights reserved.

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