Klinikum Minden

Minden, Germany

Klinikum Minden

Minden, Germany

Time filter

Source Type

Stolzel F.,University Hospital Carl Gustav Carus Dresden | Pfirrmann M.,Ludwig Maximilians University of Munich | Aulitzky W.E.,Robert Bosch GmbH | Kaufmann M.,Robert Bosch GmbH | And 11 more authors.
Leukemia | Year: 2011

Patients with secondary acute myeloid leukemia (sAML) are generally thought to have a poor prognosis. As there are no prognostic risk stratification models for patients with sAML available, the aim of this study was to obtain a scoring system. Prognostic factors influencing overall survival (OS) and event-free survival (EFS) were analyzed in 305 sAML patients treated in the prospective AML96 trial. The obtained prognostic scoring system was then validated in an independent patient cohort included in the AML2003 and AML60 trials. In addition to the known risk factors for AML, age and karyotype, we identified the absolute platelet count and the Nucleophosmin 1 mutational status at diagnosis as prognostic factors of sAML patients. A pronounced distribution of sAML patients into three score groups was achieved showing a 2-year OS/EFS of 52/44% for patients in the low-risk group, 21/12% in the intermediate-risk group and 7/3% in the high-risk group (both P<0.001). Validation of this scoring system in a second independent set of sAML patients revealed similar significantly different survival results. In conclusion, for the first time, a prognostic scoring system is provided for sAML patients, allowing differential treatment strategies in the future. © 2011 Macmillan Publishers Limited All rights.


Neumann M.,Franklin University | Coskun E.,Franklin University | Fransecky L.,Franklin University | Mochmann L.H.,Franklin University | And 18 more authors.
PLoS ONE | Year: 2013

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup. © 2013 Neumann et al.


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.


Introduction: The aim of this study was to establish the incidence of bi-sphosphonate-related osteonecrosis of the jaws (BRONJ) in oncologic patients and to determine risk predictors with respect to this condition. Material and methods: This retrospective review included 197 oncologic patients treated from January 2005 to December 2010 with administration of bisphosphonates (BPs) as part of management. Sex, age, type of cancer diagnosed, period of substantial disease, oral surgery, type of bisphosphonate, number of doses, and cases of BRONJ diagnosis were recorded. The cumulative incidence and incidence rate of BRONJ were calculated. The factors that influenced BRONJ were assessed with multivariate logistic regression and with estimations of 95% confidence intervals and odd ratios. Values of p ≤ 0.05 were considered significant. Results: The BRONJ appeared in 9.64% of patients. The BRONJ incidence rate was 1 in 28 patients per year of BP treatment. Logistic regression showed that the odds of osteonecrosis increased 1.0172-fold with each given dose of BP. The BRONJ risk with zoledronate was 5-fold higher than that with pamidronate or ibandronate. The risk of BRONJ increased by 40-fold after dental surgery. Conclusions: Period of BP administration and type of BP used are important risk predictors for the development of BRONJ in oncologic patients treated with intravenous administration of these drugs. Patient-related factors are dental or periodontal events connected with need for oral surgery. Copyright © 2015 Termedia & Banach.


Kos M.,Klinikum Minden | Kuebler J.F.,Klinikum Minden | Luczak K.,Klinikum Minden | Engelke W.,Klinikum Minden
Journal of Cranio-Maxillofacial Surgery | Year: 2010

Introduction: The purpose of this study was to identify factors that influence bisphosphonate-related osteonecrosis of the jaws (BRONJ). Patients and methods: Patients undergoing treatment for BRONJ (n = 34) were evaluated. Sex, age, underlying diagnosis, type of bisphosphonate (BP), duration and route of administration, location of osteonecrosis, clinical symptoms, Actinomyces colonisation, treatment and outcome were recorded. Symptom onset was analysed with respect to BP potency and cumulative dose. Results: Underlying diagnoses indicating BP-treatment included multiple myeloma, breast carcinoma, prostate carcinoma and osteoporosis. In 31 patients, BRONJ was preceded by tooth extraction, root apicotomy, ill-fitting dentures, cystenucleation, implant insertion or trauma; in 3 patients, the precipitating event was not identified. Actinomyces colonisation was observed in 18 patients (53%). The occurrence of BRONJ was not directly related to BP dose or potency. More women with multiple myeloma had BRONJ than did males. BRONJ was observed in osteoporotic patients treated with both corticosteroids and BPs. Conclusions: BRONJ was not primarily associated with BP potency or dose. Factors that increased the risk of osteonecrosis were female sex, oral surgery and corticosteroids plus intravenous or oral BP administration. BP deposition in the jaw bones might enhance BRONJ by promoting bacterial colonisation; however, this hypothesis requires more study. © 2009 European Association for Cranio-Maxillo-Facial Surgery.


Kos M.,Klinikum Minden
Medical Hypotheses | Year: 2011

A specific chemical structure of bisphosphonates (BPs) determines their ability to inhibit bone resorption. Because of that they have been successfully used for several years to treat skeletal events in neoplasia, hypercalcemia of malignancy, osteoporosis, Paget's disease, osteogenesis imperfecta and fibrous dysplasia. Recently, bisphosphonate related osteonecrosis of the jaws (BRONJ) has been reported as a serious complication of therapy with these compounds. According to the currently recognised theory of its origin arrest of the osteoclast function not only reflects in diminished bone resorption, but also in reduced bone formation, both leading to decreased bone turnover and consequently to the bone necrosis.A novel hypothesis assumes that BRONJ is supported by increased bacterial adhesion to bone coated with BPs. It could be mediated by proteins termed "microbial surface components which recognise adhesive matrix molecules" (MSCRAMM). It has been found that binding of Gram-positive strains was due to the amino-terminal domain of MSCRAMM structure and that this interaction played significant role in the pathogenesis of infection. The cationic amino group of nitrogen containing BPs may attract bacteria by direct electrostatic interaction, through a direct surface protein interaction or by providing an amino acid mimic on the surface of the bony hydroxyapatite which interacts with MSCRAMM component and mediates increased bacterial adhesion. Bone exposition during dental surgical procedures acts as a trigger opening the door for bacterial invasion. That is why a strong correlation between BRONJ and dental surgical procedures exists. The jaw bones are especially subjected to infection due to thin epithelial line coating their surface, susceptibility to trauma, and presence of teeth. © 2011 Elsevier Ltd.


Kos M.,Klinikum Minden | Brusco D.,Klinikum Minden | Kuebler J.,Klinikum Minden | Engelke W.,Klinikum Minden
International Journal of Oral and Maxillofacial Surgery | Year: 2010

This retrospective study aimed to evaluate the role of bisphosphonates in jaw osteomyelitis. 29 patients were included: 18 had been treated with bisphosphonates (12 with multiple myelomas, 3 with breast carcinomas, 2 with prostate carcinomas, and 1 with osteoporosis). Of 11 control patients, 2 had breast carcinomas, 2 had bronchial carcinomas, and 7 had no cancer. Descriptive and statistical evaluations were conducted to investigate the influence of chemotherapy, corticosteroids, stem cell transplantation, and bisphosphonates on the development and clinical picture of osteomyelitis. Both groups had similar disease histories, clinical pictures, treatment methods, and outcome. Wound dehiscence frequencies were also similar (Mann-Whitney rank sum test 1.66 ± 1.5 vs. 1.45 ± 2.0 p = 0.393). Chemotherapy, steroid therapy, stem cell transplantation, or bisphosphonate administration did not correlate with the clinical picture. Neither the duration of therapy nor the type of bisphosphonate influenced the clinical picture (negative Fisher's tests). The bisphosphonate group showed a characteristic settlement of Actinomyces in the exposed bone (positive Fisher's test, p = 0.021). These results suggested that osteomyelitis developed as a consequence of the simultaneous, cumulative action of many factors. Bisphosphonates played a role comparable to other predisposing features. Coating the jaws with bisphosphonates could promote the settlement of Actinomyces. © 2010 International Association of Oral and Maxillofacial Surgeons.


Introduction: To assess the association of oral hygiene, dental caries, and periodontal status with bisphosphonate-related osteonecrosis of the jaws. Material and methods: A retrospective case-control study on 81 patients treated for neoplasms with bone metastases. Twenty-nine patients with bone necrosis and 52 controls treated with bisphosphonates were compared using the Oral Hygiene Index, Decay, Missing, Filled Teeth, Community Periodontal Index of Treatment Needs, and Residual Periodontal Bone. The null hypothesis stated that there was no difference in parameters of oral health between patients with and without bone necrosis. Differences of means of above-mentioned variables were compared between the groups with Student's t-test or Mann-Whitney rank sum test and χ2 test. Value of p . 0.05 was considered significant. Results: Poorer oral hygiene (OHIs 1.94 vs. 1.32; p = 0.065), more advanced dental caries (DMFT 26.85 vs. 22.87; p = 0.05), and more advanced periodontal disease (CPITN: = 0: 21.05% vs. 42.51%; = 1 13.16% vs. 7.29%; = 2: 0% vs. 15.38%; = 3: 65.79% vs. 28.34%; = 4: 0% vs. 6.48%, Residual periodontal bone 73.1% vs. 80.51%; p = 0,001) were characteristic of patients with bisphosphonate related jaw necrosis when compared with control group. An advanced dental caries or periodontal disease required surgical intervention which directly contributed to the development of the bone necrosis. Conclusions: Dental and periodontal disease can lead to bisphosphonate-related osteonecrosis of the jaw. Oncologic patients treated with bisphosphonates should be offered preventive care to reduce dental plaque, calculus, dental caries, and periodontal disease.


PubMed | Klinikum Minden
Type: Journal Article | Journal: Archives of medical science : AMS | Year: 2015

The aim of this study was to establish the incidence of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in oncologic patients and to determine risk predictors with respect to this condition.This retrospective review included 197 oncologic patients treated from January 2005 to December 2010 with administration of bisphosphonates (BPs) as part of management. Sex, age, type of cancer diagnosed, period of substantial disease, oral surgery, type of bisphosphonate, number of doses, and cases of BRONJ diagnosis were recorded. The cumulative incidence and incidence rate of BRONJ were calculated. The factors that influenced BRONJ were assessed with multivariate logistic regression and with estimations of 95% confidence intervals and odd ratios. Values of p 0.05 were considered significant.The BRONJ appeared in 9.64% of patients. The BRONJ incidence rate was 1 in 28 patients per year of BP treatment. Logistic regression showed that the odds of osteonecrosis increased 1.0172-fold with each given dose of BP. The BRONJ risk with zoledronate was 5-fold higher than that with pamidronate or ibandronate. The risk of BRONJ increased by 40-fold after dental surgery.Period of BP administration and type of BP used are important risk predictors for the development of BRONJ in oncologic patients treated with intravenous administration of these drugs. Patient-related factors are dental or periodontal events connected with need for oral surgery.

Loading Klinikum Minden collaborators
Loading Klinikum Minden collaborators