Friedrich Wimazal

Medical University of Vienna, Wien, Vienna, Austria

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Publications (55)188.95 Total impact

  • No preview · Article · Apr 2015 · Leukemia Research
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    ABSTRACT: Objectives Myelodysplastic syndromes (MDS) are typical diseases of the elderly. The clinical outcome of a well-characterized cohort of patients with MDS was analyzed for prevalence and impact of comorbidities to establish the basis for tailored treatment algorithms. Focus was on age- and sex-related differences. Material and Methods The hematopoietic cell transplantation-comorbidity index (HCT-CI) was assessed in 616 well-defined patients from the Austrian MDS platform (median age: 71 years). Results Most patients displayed one (24.5%) or more (23.7%) comorbidities. The highest frequencies were observed for cardiovascular disease (28.4%), diabetes (12.2%), and prior tumors (9.9%). Comorbidities were more frequent (mean number: 0.92 vs. 0.74 [male vs. female]; p = 0.030) and more severe in men than in women (mean HCT-CI score: 1.41 vs. 1.09 [male vs. female]; p = 0.016). Elderly patients (65 + years) showed a higher prevalence of comorbidities than younger patients (HCT-CI score: 1.52, mean in 65 +, vs. 0.24 and 0.76 in < 45 years and 46–65 years, respectively) (p < 0.001). These differences were most pronounced for cardiovascular disease, diabetes, and prior tumors (p < 0.001). Presence of cardiac arrhythmia or prior solid tumor was significantly associated with shorter overall survival (p = 0.023, 0.024, respectively). Moreover, HCT-CI risk grouping remained an independent prognostic parameter for survival in multivariate analysis. Conclusions Comorbidities impact clinical outcome in elderly patients with MDS. Distinct diseases cluster in an age- and sex-related manner, which may have clinical implications when designing individualized therapies. Comorbidities should be evaluated with established scores and integrated in decision making.
    No preview · Article · Jul 2014 · Journal of Geriatric Oncology
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    ABSTRACT: KIT D816V is present in a majority of patients with systemic mastocytosis (SM). We determined the KIT D816V allele burden by quantitative real-time PCR in bone marrow and peripheral blood of 105 patients with mastocytosis. KIT D816V was detected in 92/105 patients (88%). Significant differences in the median allele burden were observed between disease subgroups: cutaneous mastocytosis (0.042%), indolent SM (0.285%), smoldering SM (5.991%), aggressive SM (9.346%), and SM with associated hematologic non-mast cell lineage disease (3.761%) (P < 0.001). The KIT D816V burden also correlated with serum tryptase (R = 0.5, P < 0.005) but not with mast cell infiltration in bone marrow or mediator symptoms. Moreover, the allele burden was of prognostic significance regarding survival (P < 0.01). Patients responding to cytoreductive therapy showed a significant decrease in KIT D816V (P < 0.05). To conclude, the KIT D816V burden correlates with the variant of mastocytosis, predicts survival, and is a valuable follow-up parameter in SM.
    No preview · Article · Apr 2014 · Allergy
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    ABSTRACT: In a retrospective study, 43 patients with dysplastic neoplasms of the bone marrow (myelodysplastic syndromes and myelodysplastic/myeloproliferative-overlap neoplasms) associated with marked (grades 2-3) fibrosis were examined. Histopathologic and morphologic findings as well as cytogenetic and molecular results were correlated with clinical endpoints. Multilineage dysplasia (34 of 43 patients, 79 %) and hypercellular bone marrow (64 %) were found in most patients. In ten of 35 patients, poor risk karyotypes according to the International Prognostic Scoring System (IPSS) were recorded. The JAK2 V617F mutation was detected in four of 30 patients (13 %), and the KIT D816V mutation was found in two of 30 patients (6 %). Patients were mainly treated with palliative drugs and best supportive care. After an observation time of 1-41 (median 21) months, ten of 43 patients (23 %) had developed a secondary acute leukemia. The median survival of all 43 patients was 21.4 months (range 1.8-88.2 months). Of all prognostic parameters examined, the blast cell count at diagnosis was found to be a most reliable and most predictive marker concerning survival and leukemia progression. This confirms previous studies in dysplastic bone marrow neoplasms without fibrosis.
    No preview · Article · Nov 2013 · Annals of Hematology
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    ABSTRACT: Patient selection for various therapies in myelodysplastic syndromes (MDS) is based on prognostic factors, scoring systems and the individual life expectancy. However, most established risk scores include mainly disease-related parameters and thus focus on leukaemia-transformation rather than survival. To establish a risk score optimized for prediction of survival, we analysed international prognostic scoring system (IPSS)-related and IPSS-independent variables in 400 patients with primary MDS (median age: 71 years; range 18-91) of the Austrian MDS platform. Patients were randomly split into a learning sample (60%) and validation sample (40%). External validation was performed on 93 patients from the Heinrich Heine University (Duesseldorf/Germany). By multivariate analysis, IPSS, ferritin, age and comorbidities were found to be independent predictive variables concerning survival. Based on weighing these prognostic parameters against each other, we established a novel survival score employing IPSS, ferritin (< 900 ng/mL = 0; ≥ 900 ng/mL = 1), age (< 70 years = 0; 70-79 years = 1; ≥ 80 years = 1·5) and HCT-CI comorbidity (low/intermediate = 0; high = 0·5). Using this score, four prognostic risk groups could be discriminated in the validation sample, with highly significant differences in life expectancy [median survival: LowS (score 0), not reached; Int-1S (score 0·5-1·0), 3·84 years; Int-2S (score 1·5-2·0): 2·72 years; and HighS (score > 2·0): 0·80 years; P < 0·0001]. Our newly proposed score may be a useful tool for survival prediction in MDS and helpful in patient selection for various therapies in daily practice and clinical trials.
    No preview · Article · Aug 2013 · European Journal of Clinical Investigation
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    ABSTRACT: Mastocytosis is a group of rare diseases characterized by abnormal expansion and accumulation of tissue mast cells in various organ systems. The disease can be divided into cutaneous and systemic variants. Although considered a rare pathologic condition, more and more patients are currently diagnosed as suffering from mastocytosis. The increasing incidence is best explained by enhanced awareness and improved diagnostics in the Western world. This has in turn created a need to establish optimal facilities for the diagnosis, management, and therapy of patients with mastocytosis. In 2002, the European Competence Network on Mastocytosis (ECNM) was established, with the aim to provide all available information to doctors and patients, and to improve management and therapy of mastocytosis in Europe. Within the ECNM, Centers of Excellence and Reference Centers have been defined and inaugurated. In addition, several countries established a local network of competence within the ECNM. In 2011, the Austrian Competence Network on Mastocytosis (AUCNM) was inaugurated. The AUCNM serves as an integral part and essential partner of the ECNM. In the current article, the structure, aims, achievements, and ongoing projects of the AUCNM are presented.
    No preview · Article · Jun 2013 · memo - Magazine of European Medical Oncology
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    ABSTRACT: Systemic mastocytosis (SM) is a hematopoietic neoplasm characterized by pathologic expansion of tissue mast cells in one or more extracutaneous organs. In most children and most adult patients, skin involvement is found. Childhood patients frequently suffer from cutaneous mastocytosis without systemic involvement, whereas most adult patients are diagnosed as suffering from SM. In a smaller subset of patients, SM without skin lesions develops which is a diagnostic challenge. In the current article, a diagnostic algorithm for patients with suspected SM is proposed. In adult patients with skin lesions and histologically confirmed mastocytosis in the skin (MIS), a bone marrow biopsy is recommended regardless of the serum tryptase level. In adult patients without skin lesions who are suffering from typical mediator-related symptoms, the basal serum tryptase level is an important diagnostic parameter. In those with slightly elevated tryptase (15-30 ng/ml), additional non-invasive investigations, including a KIT mutation analysis of peripheral blood cells and sonographic analysis, is performed. In adult patients in whom i) KIT D816V is detected or/and ii) the basal serum tryptase level is clearly elevated (> 30 ng/ml) or/and iii) other clinical or laboratory features are suggesting the presence of occult mastocytosis, a bone marrow biopsy should be performed. In the absence of KIT D816V and other indications of mastocytosis, no bone marrow investigation is required, but the patient's course and the serum tryptase levels are examined in the follow-up.
    Full-text · Article · May 2013 · American Journal of Blood Research
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    ABSTRACT: Mediator-related symptoms in patients with systemic mastocytosis (SM) range from mild episodic to severe life-threatening events. We examined a series of 137 consecutive patients with mastocytosis (63 females and 74 males) referred to our center between 1988 and 2010. Almost all patients received prophylactic histamine receptor (HR1 and HR2) antagonists. Forty-two patients suffered from one or more mediator-related symptoms (hypotension, headache, flush, abdominal cramping, diarrhea) requiring therapy (SM(SY)). Severe life-threatening events (grade IV) occurred in 17 patients (12%). In 4 of these 17 patients, a deteriorating clinical course was recorded. One patient died of an apallic syndrome 1.5 years after an hymenoptera sting and cerebral hypoxia. One patient was disabled for months after an insect sting and cerebral hypoxia. Two patients with smoldering SM (SSM) suffered from severe recurrent hypotension requiring hospitalization and repeated resuscitation. Symptoms in these SSM patients did not respond to any of the antimediator-type drugs applied. However, after therapy with cladribine (2CdA), a major durable response was obtained in both cases. In patients with aggressive SM and mast cell leukemia (n = 6), life-threatening mediator-related events (grade IV) were not recorded. SM may be accompanied by life-threatening mediator-related symptoms. Most of these patients have indolent SM or SSM. In patients with SSM(SY) with uncontrolled symptoms (grade IV), therapy with 2CdA should be considered.
    No preview · Article · Nov 2011 · International Archives of Allergy and Immunology
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    ABSTRACT: It is now generally appreciated that hematologic neoplasms can develop over many years if not decades, often being initially occult or showing minimal (subdiagnostic) abnormalities. However, whereas such early neoplastic conditions have been defined in some detail in lymphoproliferative neoplasms, little is known about minimal lesions preceding the manifestation of an overt myeloid neoplasm, about underlying mechanisms, the clinical course and outcome, and the prognostic significance of such conditions. Members of several groups have recently described two 'premalignant' myeloid conditions, namely idiopathic cytopenia of undetermined significance (ICUS) and idiopathic bone marrow dysplasia of uncertain significance (IDUS). At least in some patients these are neoplastic conditions. Both conditions may progress to an overt myelodysplastic syndrome (MDS), but may also progress to another myeloid neoplasm such as acute myeloid leukemia, a myeloproliferative neoplasm (MPN), or a mast cell disorder (mastocytosis). In ICUS the dysplasia is mild and does not fulfill the WHO criteria for MDS but cytopenias can be severe. In IDUS the dysplasia is prominent but cytopenias, if detectable, are mild. In both conditions it is possible that a neoplastic clone has already replaced most or all of normal bone marrow cells when ICUS or IDUS is detected, but evidence to support this possibility is not necessarily available. For both groups of patients we recommend a thorough hematologic follow up because of the potential of disease-manifestation and the unpredictable form and time of progression. In the present review, we discuss current concepts relating to ICUS and IDUS as well as diagnostic approaches and available criteria.
    No preview · Article · Sep 2011 · Leukemia research

  • No preview · Article · May 2011 · Leukemia Research
  • Peter Valent · Friedrich Wimazal · Wolfgang R. Sperr · Hans-Peter Horny
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    ABSTRACT: A classification for myelodysplastic syndromes (MDS) has been proposed by several working groups and the World Health Organization (WHO). The recently updated criteria of the WHO are useful for discriminating MDS variants from each other. Moreover, minimal diagnostic criteria for MDS have been defined. In a few patients with unexplained cytopenia or dysplasia these criteria are not met. For these patients, the terms idiopathic cytopenia of unknown significance (ICUS) and idiopathic dysplasia of unknown significance (IDUS) have been proposed. Both conditions may progress to overt MDS over time. Therefore, once diagnosed, these patients should have a hematologic follow up. The final diagnosis of MDS has to be based on defined criteria and exclusion of all other causes of cytopenia and dysplasia, which requires detailed and sometimes extensive investigations, including a bone marrow biopsy, immunohistochemical studies, cytogenetic analysis, molecular studies, and flow cytometry. A diagnostic challenge is the potential co-existence of two myeloid neoplasms producing cytopenia or/and dysplasia in one patient. Once diagnosed, patients with MDS should be classified according to FAB and WHO criteria, and their risk concerning survival and AML evolution should be estimated by employing patient-related and disease-related risk factors, and established scoring systems, including the IPSS and/or WPSS, both of which are global standard. KeywordsMDS-Diagnostic criteria-ICUS-IDUS-IPSS
    No preview · Chapter · Mar 2011
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    ABSTRACT: Minimal diagnostic criteria for myelodysplastic syndromes (MDS) include constant cytopenia recorded for at least 6 months, dysplasia, and exclusion of other causes of cytopenia and dysplasia. However, there are patients with dysplastic bone marrow features with or without a karyotype, who have only mild if any cytopenia. This condition has been termed idiopathic dysplasia of unknown significance (IDUS). Out of a series of 1,363 patients with suspected MDS or mild cytopenia seen between 1997 and 2010, we have identified 10 patients with IDUS, and analyzed their clinical course and outcome as well as features potentially involved in disease-evolution. Follow-up ranged between 2 and 13 years. Progression to an overt myeloid neoplasm was observed in 4 patients: two progressed to frank MDS, one to chronic myelomonocytic leukemia, and one to a myelodysplastic/myeloproliferative neoplasm exhibiting 5q-and JAK2 V617F. Consecutive studies revealed that most IDUS patients have an adequate production of erythropoietin (EPO) and sufficient numbers of EPO-responsive erythroid progenitors, features rarely seen in MDS. The erythropoiesis-promoting JAK2 mutation V617F was only detectable in one case. We hypothesize that the dysplastic clone in IDUS cannot manifest as frank MDS because i) the clone retains responsiveness against EPO, and ii) an adequate EPO-production counteracts anemia. Evolution of IDUS to low risk MDS may thus depend on the biological properties of the clone as well as patient-related factors such as EPO production. The latter often decreases with age and may thus explain why MDS often manifests in the elderly.
    Preview · Article · Jan 2011 · American Journal of Cancer Research
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    ABSTRACT: The diagnosis, classification, and prognostication of patients with myelodysplastic syndromes (MDS) are usually based on clinical parameters, analysis of peripheral blood and bone marrow smears, and cytogenetic determinants. However, a thorough histologic and immunohistochemical examination of the bone marrow is often required for a final diagnosis and exact classification in these patients. Notably, histology and immunohistology may reveal dysplasia in megakaryocytes or other bone marrow lineages and/or the presence of clusters of CD34-positive precursor cells. In other cases, histology may reveal an unrelated or co-existing hematopoietic neoplasm, or may support the conclusion the patient is suffering from acute myeloid leukemia rather than MDS. Moreover, histologic investigations and immunohistology may reveal an increase in tryptase-positive cells, a coexisting systemic mastocytosis, or bone marrow fibrosis, which is of prognostic significance. To discuss diagnostic algorithms, terminologies, parameters, and specific issues in the hematopathologic evaluation of MDS, a Working Conference involving a consortium of US and EU experts, was organized in June 2010. The outcomes of the conference and resulting recommendations provided by the faculty, are reported in this article. These guidelines should assist in the diagnosis, classification, and prognostication in MDS in daily practice as well as in clinical trials.
    Full-text · Article · Nov 2010 · Oncotarget
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    ABSTRACT: Lineage involvement and maturation arrest are considered to have prognostic significance in patients with myelodysplastic syndromes (MDS). However, although the prognostic value of neutropenia, thrombocytopenia, and monocytosis have been documented, little is known about the impact of eosinophils and basophils. The authors examined the prognostic significance of eosinophils and basophils in 1008 patients with de novo MDS. Patients were enrolled from 3 centers of the Austrian-German MDS Working Group and were analyzed retrospectively. Blood eosinophils and basophils were quantified by light microscopy, and their impact on survival and leukemia-free survival was calculated by using Cox regression. Eosinophilia (eosinophils >350/microL) and basophilia (basophils >250/microL) predicted a significantly reduced survival (P < .05) without having a significant impact on leukemia-free survival. In multivariate analysis, eosinophilia and basophilia were identified as lactate dehydrogenase (LDH)-independent prognostic variables with International Prognostic Scoring System (IPSS)-specific impact. Although elevated LDH was identified as a major prognostic determinant in IPSS low-risk, intermediate-1 risk, and high-risk subgroups, the condition "eosinophilia and/or basophilia" was identified as a superior prognostic indicator in the IPSS intermediate-2 risk subgroup. The evaluation of eosinophils and basophils in patients with MDS was helpful and may complement the spectrum of variables to optimize prognostication in MDS.
    Full-text · Article · May 2010 · Cancer
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    ABSTRACT: The evaluation of comorbidity is of increasing importance in patients with hematologic disorders. In the present study, the influence of comorbidity on survival and acute myeloid leukemia (AML) evolution was analyzed retrospectively in 419 patients with de novo myelodysplastic syndromes (MDS) (observation period: 1985-2007). The median age was 71 years (range 24-91 years). Two different scoring systems, the hematopoietic stem-cell transplantation-specific comorbidity index (HCT-CI) and the Charlson comorbidity index (CCI) were applied. The HCT-CI was found to be a significant prognostic factor for overall survival (OS, P < 0.05) as well as event-free survival (EFS, P < 0.05) in our patients, whereas the CCI was of prognostic significance for OS (P < 0.05), but not for EFS. For AML-free survival, neither the HCT-CI nor the CCI were of predictive value. A multivariate analysis including age, lactate dehydrogenase, ferritin, karyotype, number of cytopenias, French-American-British groups, and comorbidity was applied. Comorbidity was found to be an independent prognostic factor in patients with low- or int-1-risk MDS (P < 0.05) regarding OS and EFS. Together, our data show that comorbidity is an important risk factor for OS and EFS in patients with MDS.
    No preview · Article · Jul 2009 · Annals of Oncology
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    ABSTRACT: Transfusion-related morbidity is an emerging problem in chronically transfused patients with myelodysplastic syndromes (MDS). Although several iron-chelating drugs are available, the optimal way of treatment of iron-overload remains uncertain. A major disadvantage of deferoxamine is that the drug has to be applied as continuous subcutaneous infusion. Therefore, novel oral agents have been developed. One of these drugs is deferasirox (Exjade). We report on 14 MDS patients who were treated with deferasirox (500-1500 mg daily) for up to 24 months. In these patients, treatment responses were recorded by determining serum ferritin levels before and during therapy and by applying recently established response criteria. In all patients except one, ferritin levels decreased during therapy. Four patients showed a complete response, one a minor response and five a stable iron load. In the responding patients, initially elevated liver enzymes decreased substantially. No substantial change in transferrin saturation or transfusion frequency was recorded. Side effects were mild and tolerable in most patients. In one patient, treatment with deferasirox was stopped because of impaired kidney function. Our data show that treatment with deferasirox is a reasonable approach to counteract iron overload in patients with MDS.
    No preview · Article · Apr 2009 · European Journal of Clinical Investigation
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    ABSTRACT: Criteria, scoring systems, and treatment algorithms for myelodysplastic syndromes (MDS) have been updated repeatedly in recent years. This apparently results from increased awareness and early recognition of the disease, an increasing number of new diagnostic and prognostic markers and tools, and new therapeutic options that may change the course and thus prognosis in MDS. To address these challenges and to create useful new diagnostic and prognostic parameters and scores, the German-Austrian Working Group for Studying Prognostic Factors in MDS was established in 2003 and later was extended to centers in Switzerland (D-A-CH group). In addition, the group cooperates with the European LeukemiaNet, the MDS Foundation, and other national and international working groups in order to improve diagnosis and prognostication. The current article represents a meeting report from the latest workshop organized by the group in Vienna in October 2008.
    Full-text · Article · Feb 2009 · Annals of Hematology
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    ABSTRACT: Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms that are preferentially diagnosed in the elderly. With the increase in older patients with MDS in the Western world and the availability of more therapeutic options, new strategies and algorithms for optimal management and treatment of these patients must be developed. Although age is recognized as an important adverse variable affecting survival, most scoring systems have not included age in score risk calculations. Comorbidity is of particular importance and a frequent covariable in elderly patients with MDS. However, although comorbidity scores have been established and used for risk assessment in younger high-risk patients scheduled to undergo intensive therapy, these scores are only just being applied to elderly patients, with relevant results. Advanced age should not exclude a patient with MDS from appropriate treatment, and age alone should not be considered a surrogate marker for functional decline or comorbidities. This article discusses the need to improve scoring systems, individualized risk-assessment, and treatment algorithms for elderly patients with MDS by including age and comorbidities.
    No preview · Article · Nov 2008 · Journal of the National Comprehensive Cancer Network: JNCCN
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    ABSTRACT: Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and a tendency to transition to acute myeloid leukemia. Due to the increasing number of older patients in Austria and the high frequency of therapy-associated MDS following successful chemo- and/or radiotherapy of a primary tumor, the frequency and relevance of MDS are continuously increasing. While therapeutic options were until recently limited to best supportive care, AML-like induction chemotherapy and hematopoietic stem cell transplantation (HSCT) in younger patients, in recent years new therapeutic options have become available. Supportive care was improved through the introduction of effective iron chelation and the availability of hematopoietic growth factors like erythropoiesis-stimulating factors (ESF) and granulocyte colony-stimulating factors (G-CSF). In addition, immune-modulating drugs (IMiDs) like lenalidomide or epigenetically effective agents like the cytosine analogues or histone deacetylase (HDAC) inhibitors have become available and are highly effective in distinct subgroups of MDS patients. The development of state-of-the art recommendations is one of the major aims of the MDS Platform of the Austrian Society of Hematology and Oncology. This manuscript reviews recent developments in clinical scoring and targeted and individualized MDS therapy and discusses their relevance in and potential applicability to daily practice.
    No preview · Article · Aug 2008 · Wiener klinische Wochenschrift
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    ABSTRACT: Basophilic crisis and eosinophilia are well recognized features of advanced chronic myeloid leukaemia. In other myeloid neoplasms, however, transformation with marked basophilia and eosinophilia is considered unusual. We examined the long-term follow-up of 322 patients with de novo myelodysplastic syndromes (MDS) to define the frequency of basophilic, eosinophilic and mixed lineage (basophilic and eosinophilic) transformation. Of all patients, only one developed mixed lineage crisis (>or= 20% basophils and >or= 20% eosinophils). In this patient, who initially suffered from chronic myelomonocytic leukaemia, basophils increased to 48% and eosinophils up to 31% at the time of progression. Mixed lineage crisis was not accompanied by an increase in blast cells or organomegaly. The presence of BCR/ABL and other relevant fusion gene products (FIP1L1/PDGFRA, AML1/ETO, PML/RAR alpha, CBF beta/MYH11) were excluded by PCR. Myelomastocytic transformation/myelomastocytic leukaemia and primary mast cell disease were excluded by histology, KIT mutation analysis, electron microscopy and immunophenotyping. Basophils were thus found to be CD123+, CD203c+, BB1+, KIT- cells, and to express a functional IgE-receptor. Among the other patients with MDS examined, 4(1.2%) were found to have marked basophilia (>or= 20%) and 7(2.1%) were found to have massive eosinophilia ( >or= 20%), whereas mixed-lineage crisis was detected in none of them. Mixed basophil/eosinophil crisis may develop in patients with MDS but is an extremely rare event.
    No preview · Article · Jul 2008 · European Journal of Clinical Investigation

Publication Stats

1k Citations
188.95 Total Impact Points


  • 2004-2014
    • Medical University of Vienna
      • • Department of Obstetrics and Gynecology
      • • Institute for Social Medicine
      Wien, Vienna, Austria
  • 2008
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2007
    • Hanusch Krankenhaus
      Wien, Vienna, Austria
  • 1999-2004
    • University of Vienna
      • • Universitätsklinik für Innere Medizin I
      • • Institute of Histology and Embryology
      Vienna, Vienna, Austria