Klinikum Nord

Nürnberg, Germany

Klinikum Nord

Nürnberg, Germany

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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.


Von Weikersthal L.F.,Klinikum Sankt Marien | Schalhorn A.,Ludwig Maximilians University of Munich | Stauch M.,Oncological Practice | Quietzsch D.,Klinikum Chemnitz | And 16 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.


Morton D.L.,The Surgical Center | Thompson J.F.,University of Sydney | Cochran A.J.,University of California at Los Angeles | Mozzillo N.,Italian National Cancer Institute | And 16 more authors.
New England Journal of Medicine | Year: 2014

Background: Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. Methods: We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results: No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (±SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3±1.8% vs. 64.7±2.3%; hazard ratio for recurrence or metastasis, 0.76; P = 0.01), and those with thick melanomas, defined as >3.50 mm (50.7±4.0% vs. 40.5±4.7%; hazard ratio, 0.70; P = 0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma- specific survival rate was 62.1±4.8% among those with metastasis versus 85.1±1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0±7.0% and 64.6±4.9% (hazard ratio, 1.75; P = 0.03). Biopsy-based management improved the 10-year rate of distant disease-free survival (hazard ratio for distant metastasis, 0.62; P = 0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P = 0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted. Conclusions: Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease-free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. Copyright © 2014 Massachusetts Medical Society. All rights reserved.


Middeke J.M.,TU Dresden | Herold S.,TU Dresden | Herold S.,German Cancer Research Center | Rucker-Braun E.,TU Dresden | And 24 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.


Schaich M.,Universitatsklinikum Cg Carus | Rollig C.,Universitatsklinikum Cg Carus | Soucek S.,Universitatsklinikum Cg Carus | Kramer M.,Universitatsklinikum Cg Carus | And 16 more authors.
Journal of Clinical Oncology | Year: 2011

Purpose: To assess the optimal cumulative dose of cytarabine for treatment of young adults with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods: Between 1996 and 2003, 933 patients (median age, 47 years; range 15 to 60 years) with untreated AML were randomly assigned at diagnosis to receive cytarabine within the first consolidation therapy at either a intermediate-dose of 12 g/m2 (I-MAC) or a high-dose of 36 g/m2 (H-MAC) combined with mitoxantrone. Autologous hematopoietic stem-cell transplantation or intermediate-dose cytarabine (10 g/m2) were offered as second consolidation. Patients with a matched donor could receive an allogeneic transplantation in a risk-adapted manner. Results: After double induction therapy including intermediate-dose cytarabine (10 g/m2), mitoxantrone, etoposide, and amsacrine, complete remission was achieved in 66% of patients. In the primary efficacy analysis population, a consolidation with either I-MAC or H-MAC did not result in significant differences in the 5-year overall (30% v 33%; P = .77) or disease-free survival (37% v 38%; P = .86) according to the intention-to-treat analysis. Besides a prolongation of neutropenia and higher transfusion demands in the H-MAC arm, rates of serious adverse events were comparable in the two groups. Conclusion: In young adults with AML receiving intermediate-dose cytarabine induction, intensification of the cytarabine dose beyond 12 g/m2 within first consolidation did not improve treatment outcome. © 2011 by American Society of Clinical Oncology.


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.


Rollig C.,Universitatsklinikum Dresden | Bornhauser M.,Universitatsklinikum Dresden | Thiede C.,Universitatsklinikum Dresden | Taube F.,Universitatsklinikum Dresden | And 13 more authors.
Journal of Clinical Oncology | Year: 2011

Purpose: The current European LeukemiaNet (ELN) recommendations for acute myeloid leukemia (AML) propose a new risk reporting system, integrating molecular and cytogenetic factors and subdividing the large heterogenous group of intermediate-risk patients into intermediate-I (IR-I) and intermediate-II (IR-II). We assessed the prognostic value of the new risk classification in a large cohort of patients. Patients and Methods: Complete data for classification were available for 1,557 of 1,862 patients treated in the AML96 trial. Patients were assigned to the proposed genetic groups from the ELN recommendations, and survival analyses were performed using the Kaplan-Meier method and log-rank test for significance testing. Results: The median age of all patients was 67 years. With a median follow-up of 8.3 years, significant differences between all risk categories were observed in patients age ≤ 60 years regarding the time to relapse, relapse-free survival, and overall survival (OS). Patients in the IR-II group had a better prognosis than patients in the IR-I group. The median OS times in young patients with favorable risk (FR), IR-I, IR-II, and adverse risk (AR) were 5.3, 1.1, 1.6, and 0.5 years, respectively. Separate analyses in the age group older than 60 years revealed significant differences between FR, AR, and IR as a whole, but not between IR-I and IR-II. Conclusion: In younger patients with AML, the ELN classification seems to be the best available framework for prognostic estimations to date. Caution is advised concerning its use for prospective treatment allocation before it has been prospectively validated. In elderly patients, alternative prognostic factors are desirable for further risk stratification of IR. © 2011 by American Society of Clinical Oncology.


Rollig C.,Universitatsklinikum Dresden | Thiede C.,Universitatsklinikum Dresden | Gramatzki M.,Universitatsklinikum Schleswig Holstein | Aulitzky W.,Robert Bosch GmbH | And 15 more authors.
Blood | Year: 2010

We present an analysis of prognostic factors derived from a trial in patients with acute myeloid leukemia older than 60 years. The AML96 trial included 909 patients with a median age of 67 years (range, 61-87 years). Treatment included cytarabine-based induction therapy followed by 1 consolidation. The median follow-up time for all patients is 68 months (5.7 years). A total of 454 of all 909 patients reached a complete remission (50%). Five-year overall survival (OS) and disease-free survival were 9.7% and 14%, respectively. Multivariate analyses revealed that karyotype, age, NPM1 mutation status, white blood cell count, lactate dehydrogenase, and CD34 expression were of independent prognostic significance for OS. On the basis of the multivariate Cox model, an additive risk score was developed that allowed the subdivision of the largest group of patients with an intermediate-risk karyotype into 2 groups. We are, therefore, able to distinguish 4 prognostic groups: favorable risk, good intermediate risk, adverse intermediate risk, and high risk. The corresponding 3-year OS rates were 39.5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy. This study was registered at www.clinicaltrials.gov as #NCT00180115. © 2010 by The American Society of Hematology.

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