Middeke J.M.,TU Dresden |
Fang M.,Fred Hutchinson Cancer Research Center |
Cornelissen J.J.,Erasmus Medical Center |
Mohr B.,TU Dresden |
And 16 more authors.
Blood | Year: 2014
Patients with acute myeloid leukemia (AML) and abnormalities of chromosome 17p (abnl (17p)) are at high-risk of treatment failure. Poor outcomes have been reported with conventional chemotherapy. To accurately define the outcome after allogeneic hematopoietic stem cell transplantation (HSCT) in patients with abnl(17p)AML,weanalyzed the results of patients with this abnormality who received an allogeneic HSCT between January 2000 and December 2010 in 1 of 4 well-defined cohorts (Fred Hutchinson Cancer Research Center, Haemato Oncology Foundation for Adults in the Netherlands, Study Alliance Leukemia, German Cooperative Transplant Study Group). Data of 201 patients with a median age of 54 years were evaluable. At the time of analysis, 30 patients were alive with a median follow-up of 30 months. The 3-year probability of overall survival (OS) was 15% (95% confidence interval [CI], 10-20). The cumulative incidence of relapse at 3 years was49% (95% CI, 42-56). Notably, almost70% of all relapses occurred within the first 6 months after HSCT. Patients who were transplanted in first complete remission (CR1) had superior OS compared with those with advanced disease (22% vs 9%, P < .001). Our findings confirm the high-risk of treatment failure in abnl(17p) AML even after allogeneic HSCT in CR1. Although allogeneic HSCT remains a valid option in CR1, alternative treatment strategies are needed for the remaining patients. © 2014 by The American Society of Hematology.
Sukalo M.,University Hospital Magdeburg |
Fiedler A.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Guzman C.,Hospital Nacional Of Ninos |
Spranger S.,Praxis fur Humangenetik |
And 35 more authors.
Human Mutation | Year: 2014
Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD. © 2014 WILEY PERIODICALS, INC.
Lymphocyte morphology in the peripheral blood film: Proposal of a revised nomenclature and systematics [Lymphozytenmorphologie im Blutausstrich - Vorstellung einer überarbeiteten Nomenklatur und Systematik]
Baurmann H.,Stiftung Deutsche Klinik fur Diagnostik GmbH |
Bettelheim P.,St. Elisabethinen Krankenhaus |
Diem H.,Wurmtallabor |
Gassmann W.,St. Marien Krankenhaus Siegen |
Nebe T.,Hamatologisches Speziallabor
LaboratoriumsMedizin | Year: 2011
The following recommendations for the differentiation of lymphatic cells in the blood film of adults have been developed by the working group for laboratory diagnostics of the German Society of Haematology and Oncology on behalf of the German and Austrian haematological societies. The nomenclature of lymphatic cells should be harmonised in Germany and Europe and should provide a practical approach on how to differentiate lymphatic cells. The basis of the new nomenclature is the upfront classification into inconspicuous or conspicuous lymphatic cells. In a second step, the conspicuous cells are further assigned to "atypical cells, suspect reactive" or "atypical cells, suspect neoplastic". The percentages of the resulting three-way division are integrated into the differential white count. If this assignment of conspicuous cells is impossible, they are called "atypical cells, uncertain nature" in a fourth category of "diverse cells". This category of "diverse cells" also contains cells which are only rarely or never present in the normal blood film or unclear cells. The assignment to the category "diverse" essentially requires a comment in the report describing these cells and a subsequent clarification of such findings. © 2011 by Walter de Gruyter Berlin Boston.
Eickmeier O.,Goethe University Frankfurt |
Smaczny C.,Goethe University Frankfurt |
Gappa M.,Marien Hospital Wesel |
Hirche T.O.,Stiftung Deutsche Klinik fur Diagnostik GmbH |
Wagner T.O.F.,Goethe University Frankfurt
Pneumologe | Year: 2013
The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 gave hope that a causal therapy of CF would soon be available. Scientists put a lot of effort into correcting the basic defect on gene level but so far there is still no therapy available in this field. However, new therapies are available on the basis of correcting the defect on protein level due to mutation-specific therapy. More than 1,900 mutations have been described and divided into different classes depending on whether there is a complete cessation of translation (so-called stop mutations) or other functional losses. With the approval of a first, specifically effective therapy for a certain class of mutations, individualized therapy has made its way into the clinical practice for CF. In addition, progress has been achieved in the development and approval of new symptomatic therapies. Apart from CFTR it has become very clear that most of the pulmonary manifestations of CF lung disease are also determined by modifying genes and environmental factors. Important advances have been made within the last decade by introducing European standards for patient care and development of research networks as well as national and European structures for clinical trials. Hence, the basis for a systematic reorganization of therapy in CF within the next decade has been established. © 2013 Springer-Verlag Berlin Heidelberg.
Jaursch-Hancke C.,Stiftung Deutsche Klinik fur Diagnostik GmbH
Austrian Journal of Clinical Endocrinology and Metabolism | Year: 2011
Androgen Deficieny in Women: When Does It Reach Clinical Relevance? In both men and women alike, androgens have an impact on musculature, distribution of fat, sexuality, general fitness, and well-being. Contrary to men, the symptoms of hypogonadism in women are less clearly defined and reliable surrogate parameters to determine androgen deficiency in women have not been established so far. The term "hypoactive sexualdesire disorder"(HSDD) has been accepted to define clinical symptoms. Confirmed androgen deficiencies are related to surgical menopause, panhypopituitarism, Addison's disease, natural menopause, and a number of drugs that cause androgen suppression. Testosterone replacement only makes sense in the presence of clinical symptoms (HSDD). Patients must be explicitly informed that androgen replacement is not a standard treatment and that long-term safety data are still missing. Provided that the indication has been clear-cut before therapy is initiated its outcome is often very convincing.
Wehrmann T.,Stiftung Deutsche Klinik fur Diagnostik GmbH
Endoskopie Heute | Year: 2012
Since the cause of achalasia is still unknown, all currently available therapies are palliative intended and gained to essentially weaken the lower esophageal sphincter (LES). Some drugs like nitrates and calcium antagonists are able to lower the LES-pressure, however, the symptomatic improvement obtained in patients with achalasia is low, so that this strategy is at best suitable for short-term bridging to other therapies. By local injection of botulinum toxin (BTX) in the gastric cardia, a profound reduction in the LES-pressure can be achieved. Symptomatic improvement lasts for several months (about 3-9 months), however, due to re-innervation a loss of efficacy occurs, which then makes repeated injections necessary. Therefore, this treatment is indicated mainly for patients with a reduced life expectancy and/or those with anatomic risk factors (e.g. large epiphrenic diverticulum). Pneumatic dilation (PD) of the cardia, however, leads to a longer-term response (>5-10 years) in about 50% of patients, in the remaining patients a symptomatic response can usually be achieved by subsequent re-dilations (overall symptomatic improvement can be expected in almost 85%). As positive predictors for a symptomatic response to PD an age>45 years, a LES-pressure reduction <15mmHg and/or an improved radiological esophageal clearance post-PD were identified. PD has a significant risk for esophageal perforation, which occurs in about 2-3% of cases. In randomized, controlled studies BTX injection was inferior to PD and surgical cardiomyotomy, while the efficacy of PD, in patients >40 years, was nearly equivalent to surgery. © Georg Thieme Verlag KG Stuttgart. New York.
Merkle W.,Stiftung Deutsche Klinik fur Diagnostik GmbH
Urologe | Year: 2014
Prophylaxis of tumors of the prostate gland is theoretically simple but what makes it difficult is that no appropriate test methods are available. The topic of prostate cancer prophylaxis by dietary supplements remains difficult as there are still no really certain data. The psychological aspect of wanting and being able to actively contribute to success of a therapy oneself, is absolutely not an aspect to be ignored to accept such dietary supplements. There are also studies which show that a certain helpful effect seems to be present. From these considerations the question arises whether cancer prophylaxis could be developed from this. This article presents the state of the art in early 2014. © 2014, Springer-Verlag Berlin Heidelberg.
Middeke J.M.,TU Dresden |
Beelen D.,University of Duisburg - Essen |
Stadler M.,Klinik fur Hamatologie |
Gohring G.,Institute For Zell Und Molekularpathologie |
And 12 more authors.
Blood | Year: 2012
The European LeukemiaNet classification combines a heterogeneous group of aberrations as adverse-risk abnormalities. Our goal was to investigate the outcomes associated with distinct high-risk chromosomal abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). We performed a retrospective cohort analysis in patients with high-risk AML who received first, HLA-compatible, allogeneic HSCT between January 2005 and December 2008. Data from 236 patients with a median age of 55 years were included. Because complex karyotype (CK), -5/5q-, and abnl(17p) are overlapping categories, a hierarchical classification system based on the presence or absence of abnl(17p) and -5/5q- was developed. Patients with abnl(17p) had a 2-year event-free survival (EFS) of 11%(95% confidence interval [CI], 0%-25%), patients with -5/5q- but no abnl(17p) a 2-year EFS of 29% (95% CI, 14%-44%), and patients with adverse-riskAMLbut neither of the 2 marker lesions a 2-year EFS of 49% (95% CI, 39%- 59%). Notably, complex and monosomal karyotypes lost their prognostic value when these marker lesions were excluded. In conclusion, hierarchical classification of adverse-risk karyotypes by 2 marker lesions, abnl(17p) and -5/5q-, is effective in prognostication of the outcome of allogeneic HSCT in AML. © 2012 by The American Society of Hematology.
Madjar H.,Stiftung Deutsche Klinik fur Diagnostik GmbH
Breast Care | Year: 2010
Diagnosis of breast cancer has been widely improved since the development of high-resolution ultrasound equipment. In the past, ultrasound was only considered useful for the diagnosis of cysts. Meanwhile, it improves the differential diagnosis of benign and malignant lesions, local preoperative staging and guided interventional diagnosis. In dense breasts, mammography has limited sensitivity. Furthermore, women with dense parenchyma have a highly increased risk of breast cancer development. Ultrasound is useful to examine dense breast tissue. Recent studies have shown that the detection of small cancers with high-resolution ultrasound is increased by 3-4 cancers per 1,000 women without clinical or mammographic abnormalities. Furthermore, stage distribution is similar between mammographically and sonographically detected carcinomas. Ultrasound is routinely used for curative diagnosis, to overcome the limitations of mammography. However, within the mammographic screening in Germany, breast density is not considered as important. Ultrasound is only used if a suspicious lesion is detected by mammography. Interestingly, 2 years ago, a screening project started in Austria in which ultrasound is always added in cases of dense breasts. Preliminary data show that the detection of additional carcinomas is increased in the same order as shown in previous studies. Therefore, an improved cancer detection and differentiation can be expected with high-resolution ultrasound. Copyright © 2010 S. Karger AG, Basel.
Luxembourg B.,University Hospital Frankfurt |
Pavlova A.,University of Bonn |
Geisen C.,University Hospital Frankfurt |
Spannagl M.,Ludwig Maximilians University of Munich |
And 5 more authors.
Thrombosis and Haemostasis | Year: 2014
Mutations in the antithrombin (AT) gene can impair the capacity of AT to bind heparin (AT deficiency type IIHBS), its target proteases such as thrombin (type IIRS), or both (type IIPE). Type II AT deficiencies are almost exclusively caused by missense mutations, whereas type I AT deficiency can originate from missense or null mutations. In a retrospective cohort study, we investigated the impact of the type of mutation and type of AT deficiency on the manifestation of thromboem-bolic events in 377 patients with hereditary AT deficiencies (133 from our own cohort, 244 reported in the literature). Carriers of missense mutations showed a lower risk of venous thromboembolism (VTE) than those of null mutations (adjusted hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.27-0.58, p<0.001), and the risk of VTE was significantly decreased among patients with type IIHBS AT deficiency compared to patients with other types of AT deficiency (HR 0.23, 95%CI 0.13-0.41, p<0.001). The risk of pulmonary embolism complicating deep-vein thrombosis was lower in all type II AT deficiencies compared to type I AT deficiency (relative risk 0.69, 95%CI 0.56-0.84). By contrast, the risk of arterial thromboembolism tended to be higher in carriers of missense mutations than in those with null mutations (HR 6.08-fold, 95%CI 0.74-49.81, p=0.093) and was 5.9-fold increased (95%CI 1.22-28.62, p=0.028) in type IIHBS versus other types of AT deficiency. Our data indicate that the type of inherited AT defect modulates not only the risk of thromboembolism but also the localisation and encourage further studies to unravel this phenomenon. © Schattauer 2014.