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Sample records for syndromes mds prognostic

  1. Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS).

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    Yao, Chi-Yuan; Hou, Hsin-An; Lin, Tzung-Yi; Lin, Chien-Chin; Chou, Wen-Chien; Tseng, Mei-Hsuan; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Kuo, Yuan-Yeh; Wu, Shang-Ju; Liao, Xiu-Wen; Lin, Chien-Ting; Ko, Bor-Shen; Chen, Chien-Yuan; Hsu, Szu-Chun; Li, Chi-Cheng; Huang, Shang-Yi; Yao, Ming; Tang, Jih-Luh; Tsay, Woei; Liu, Chieh-Yu; Tien, Hwei-Fang

    2016-09-27

    Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS (PMDS patients. The h-MDS patients had lower incidences of RUNX1, ASXL1, DNMT3A, EZH2 and TP53 mutations than NH-MDS patients. The cumulated incidence of acute leukemic transformation at 5 years was 19.3% for h-MDS and 40.4% for NH-MDS patients (P= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS (P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS.

  2. Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS)

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    Lin, Tzung-Yi; Lin, Chien-Chin; Chou, Wen-Chien; Tseng, Mei-Hsuan; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Kuo, Yuan-Yeh; Wu, Shang-Ju; Liao, Xiu-Wen; Lin, Chien-Ting; Ko, Bor-Shen; Chen, Chien-Yuan; Hsu, Szu-Chun; Li, Chi-Cheng; Huang, Shang-Yi; Yao, Ming; Tang, Jih-Luh; Tsay, Woei; Liu, Chieh-Yu; Tien, Hwei-Fang

    2016-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS (PP= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS (P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS. PMID:27527853

  3. Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS)

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    Yao, Chi-Yuan; Hou, Hsin-An; Lin, Tzung-Yi; Lin, Chien-Chin; Chou, Wen-Chien; Tseng, Mei-Hsuan; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Kuo, Yuan-Yeh; Wu, Shang-Ju; Liao, Xiu-Wen; Lin, Chien-Ting; Ko, Bor-Shen; Chen, Chien-Yuan

    2016-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, t...

  4. Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium.

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    Zeidan, A M; Al Ali, N; Barnard, J; Padron, E; Lancet, J E; Sekeres, M A; Steensma, D P; DeZern, A; Roboz, G; Jabbour, E; Garcia-Manero, G; List, A; Komrokji, R

    2017-06-01

    While therapy-related (t)-myelodysplastic syndromes (MDS) have worse outcomes than de novo MDS (d-MDS), some t-MDS patients have an indolent course. Most MDS prognostic models excluded t-MDS patients during development. The performances of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Global Prognostic System (MPSS), WHO Prognostic Scoring System (WPSS) and t-MDS Prognostic System (TPSS) were compared among patients with t-MDS. Akaike information criteria (AIC) assessed the relative goodness of fit of the models. We identified 370 t-MDS patients (19%) among 1950 MDS patients. Prior therapy included chemotherapy alone (48%), chemoradiation (31%), and radiation alone in 21%. Median survival for t-MDS patients was significantly shorter than for d-MDS (19 vs 46 months, PMDS (PMDS had a significantly higher hazard of death relative to d-MDS in every risk model, and had inferior survival compared to patients with d-MDS within all risk group categories. AIC Scores (lower is better) were 2316 (MPSS), 2343 (TPSS), 2343 (IPSS-R), 2361 (WPSS) and 2364 (IPSS). In conclusion, subsets of t-MDS patients with varying clinical outcomes can be identified using conventional risk stratification models. The MPSS, TPSS and IPSS-R provide the best predictive power.

  5. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions.

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    Valent, Peter; Orazi, Attilio; Steensma, David P; Ebert, Benjamin L; Haase, Detlef; Malcovati, Luca; van de Loosdrecht, Arjan A; Haferlach, Torsten; Westers, Theresia M; Wells, Denise A; Giagounidis, Aristoteles; Loken, Michael; Orfao, Alberto; Lübbert, Michael; Ganser, Arnold; Hofmann, Wolf-Karsten; Ogata, Kiyoyuki; Schanz, Julie; Béné, Marie C; Hoermann, Gregor; Sperr, Wolfgang R; Sotlar, Karl; Bettelheim, Peter; Stauder, Reinhard; Pfeilstöcker, Michael; Horny, Hans-Peter; Germing, Ulrich; Greenberg, Peter; Bennett, John M

    2017-09-26

    Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms characterized by peripheral cytopenia, dysplasia, and a variable clinical course with about 30% risk to transform to secondary acute myeloid leukemia (AML). In the past 15 years, diagnostic evaluations, prognostication, and treatment of MDS have improved substantially. However, with the discovery of molecular markers and advent of novel targeted therapies, new challenges have emerged in the complex field of MDS. For example, MDS-related molecular lesions may be detectable in healthy individuals and increase in prevalence with age. Other patients exhibit persistent cytopenia of unknown etiology without dysplasia. Although these conditions are potential pre-phases of MDS they may also transform into other bone marrow neoplasms. Recently identified molecular, cytogenetic, and flow-based parameters may add in the delineation and prognostication of these conditions. However, no generally accepted integrated classification and no related criteria are as yet available. In an attempt to address this challenge, an international consensus group discussed these issues in a working conference in July 2016. The outcomes of this conference are summarized in the present article which includes criteria and a proposal for the classification of pre-MDS conditions as well as updated minimal diagnostic criteria of MDS. Moreover, we propose diagnostic standards to delineate between ´normal´, pre-MDS, and MDS. These standards and criteria should facilitate diagnostic and prognostic evaluations in clinical studies as well as in clinical practice.

  6. The need for additional genetic markers for MDS stratification: what does the future hold for prognostication?

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    Otrock, Zaher K.; Tiu, Ramon V.; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.

    2013-01-01

    Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic disorders. Metaphase cytogenetics (MC) has been the gold standard for genetic testing in MDS, but it can detect clonal cytogenetic abnormalities in only 50% of cases. New karyotyping tests include fluorescence in situ hybridization (FISH), array-based comparative genomic hybridization (aCGH), and single nucleotide polymorphism arrays (SNP-A). These techniques have increased the detected genetic abnormalities in MDS, many of which confer prognostic significance to overall and leukemia-free survival. This has eventually increased our understanding of MDS genetics. With the help of new technologies, we anticipate that the existing prognostic scoring systems will incorporate mutational data into their parameters. This review discusses the progress in MDS diagnosis through the use of array-based technologies. We also discuss the recently investigated genetic mutation in MDS, and revisit the MDS classification and prognostic scoring systems. PMID:23373781

  7. Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics.

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    Kokate, Prajakta; Dalvi, Rupa; Koppaka, Neeraja; Mandava, Swarna

    2017-10-01

    Cytogenetics is a critical independent prognostic factor in myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ hybridization (FISH) Panel Testing are extensively used for the prognostic stratification of MDS, although the FISH test is not yet a bona fide component of the International Prognostic Scoring System (IPSS). The present study compares the utility of CC and FISH to detect chromosomal anomalies and in prognostic categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/-7q, +8 and -20q was performed on whole blood or bone marrow samples from 136 patients with MDS. Chromosomal anomalies were found in 40 cases by CC, including three novel translocations. FISH identified at least one anomaly in 54/136 (39.7%) cases. More than one anomaly was found in 18/54 (33.3%) cases, therefore, overall FISH identified 75 anomalies of which 32 (42.6%) were undetected by CC. FISH provided additional information in cases with CC failure and in cases with a normal karyotype. Further, in ten cases with an abnormal karyotype, FISH could identify additional anomalies, increasing the number of abnormalities per patient. Although CC is the gold standard in the cytogenetic profiling of MDS, FISH has proven to be an asset in identifying additional abnormalities. The number of anomalies per patient can predict the prognosis in MDS and hence, FISH contributed towards prognostic re-categorization. The FISH Panel testing should be used as an adjunct to CC, irrespective of the adequacy of the number of metaphases in CC, as it improves the prognostic classification of MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Iron overload in myelodysplastic syndromes (MDS).

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    Gattermann, Norbert

    2018-01-01

    Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

  9. Management of older adults with myelodysplastic syndromes (MDS).

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    Luskin, Marlise R; Abel, Gregory A

    2017-12-28

    The myelodysplastic syndromes (MDS) are a varied group of hematologic neoplasms that lead to bone marrow failure, and also carry a risk of progression to acute myeloid leukemia. Patients with MDS suffer significant impairments to both their quality of life and survival. Age is the dominant risk factor for the development of MDS, with a median age at diagnosis over 70years. Consequently, patients with MDS frequently have concurrent comorbidities and/or frailty which may be coincident or related to the disease itself. Disease characteristics, degree of comorbidity, and presence of frailty all impact prognosis. Treatment of MDS focuses on supportive care, with disease-modifying approaches (chemotherapy and allogeneic hematopoietic cell transplantation) reserved for fit patients with high-risk disease. Care of patients with MDS requires understanding the disease in the context of an older population, and tailoring approaches to both disease risk and patient suitability for therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The prognostic value of monosomal karyotype (MK) in higher-risk patients with myelodysplastic syndromes treated with 5-Azacitidine. A retrospective analysis of the Hellenic (Greek) MDS Study Group.

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    Papageorgiou, Sotirios G; Vasilatou, Diamantina; Kontos, Christos K; Kotsianidis, Ioannis; Symeonidis, Argiris; Galanopoulos, Athanasios G; Hatzimichael, Eleftheria; Megalakaki, Aekaterini; Poulakidas, Elias; Diamantopoulos, Panagiotis; Vassilakopoulos, Theodoros; Zikos, Panagiotis; Papadaki, Helen; Mparmparousi, Despoina; Bouronikou, Eleni; Panayiotidis, Panayiotis; Viniou, Nora-Athina; Pappa, Vassiliki

    2018-04-16

    In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk MDS patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS-R, as well as with high-risk disease, according to IPSS (P=0.029), IPSS-R (PMDS treated with 5-AZA. Furthermore, we showed that in MDS with high or very-high IPSS-R risk score, MK can further distinguish patients with worse outcome. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  11. Flow cytometry in the diagnosis of myelodysplastic syndromes (MDS) and the value of myeloid nuclear differentiation antigen (MNDA).

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    Bellos, Frauke; Kern, Wolfgang

    2014-09-25

    Background: Confirming diagnosis of myelodysplastic syndromes (MDS) is often challenging. Standard diagnostic methods are cytomorphology (CM) and cytogenetics (CG). Multiparameter flow cytometry (MFC) is upcoming in MDS diagnostic work up, comparability and investigator experience are critical. Myeloid nuclear differentiation antigen (MNDA) in myelomonocytic cells might be expressed more weakly in patients with MDS. The analysis of MNDA may thus improve diagnostic capabilities of MFC in MDS. Methods: Staining methods and antibody combinations for MFC in MDS are outlined, giving details for interpretation of results in regard to dyspoiesis. MFC results are correlated with CM and CG and with survival data. Use of myeloid nuclear differentiation antigen (MNDA) in MDS diagnostics was evaluated in 239 patients with MDS, AML, other cytopenic conditions and in 30 negative controls. Results: Strong correlation between findings in CM and MFC was found; MFC results correlated well with those of CG. Patients with higher grades of dysplasia in MFC had shorter overall survival. Percentages of granulocytes and monocytes with diminished MNDA expression (%dimG, %dimM) were higher in patients with MDS and AML. Mean fluorescence intensity (MFI) of MNDA in monocytes was lower in MDS and AML. Cut-off values for %dimG (12%) and %dimM (22%) as well as for MFI in monocytes (72) were defined discriminating between MDS and non-MDS. Conclusion: MFC adds significant information on dyspoiesis in the diagnostic work up for MDS and provides prognostic information. MNDA expression can be assessed by MFC and may facilitate evaluation of dyspoiesis when added to MDS MFC panels. © 2014 Clinical Cytometry Society. Copyright © 2014 Clinical Cytometry Society.

  12. Myelodysplastic Syndromes (MDS) and autoimmune disorders (AD): cause or consequence?

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    Braun, Thorsten; Fenaux, Pierre

    2013-12-01

    Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory response of the immune system. AD accompanying MDS and CMML include vasculitis, seronegative polyarthritis and neutrophilic dermatosis. Rare AD including relapsing polychondritis is strongly associated with MDS as in a high proportion of those patients MDS is diagnosed during disease course. Antinuclear antibodies (ANA) are frequently found among MDS patients without clinical manifestation of AD. In a subset of patients, MDS and resulting cytopenias appear to be the consequence of auto reactive immunologic activity and may respond to immunosuppressive treatment (IST). Increased release of inflammatory cytokines like tumor necrosis factor-(TNF)-α and interferon (IF)-γ triggers apoptosis of myeloid precursor cells leading to cytopenias. Impaired function of immune cells including cytotoxic, regulatory (Treg), helper (Th17) T cells and NK cells also appears to predict response to IST, outcome and occurrence of AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Comparison of Myelodysplastic Syndrome Prognostic Scoring Systems

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    Özlen Bektaş

    2016-05-01

    Full Text Available Objective: Myelodysplastic syndrome (MDS is a clonal hematopoietic stem cell disease. Patients are at risk of developing cytopenias or progression to acute myeloid leukemia. Different classifications and prognostic scoring systems have been developed. The aim of this study was to compare the different prognostic scoring systems. Materials and Methods: One hundred and one patients who were diagnosed with primary MDS in 2003-2011 in a tertiary care university hospital’s hematology department were included in the study. Results: As the International Prognostic Scoring System (IPSS, World Health Organization Classification-Based Prognostic Scoring System (WPSS, MD Anderson Prognostic Scoring System (MPSS, and revised IPSS (IPSS-R risk categories increased, leukemia-free survival and overall survival decreased (p<0.001. When the IPSS, WPSS, MPSS, and IPSS-R prognostic systems were compared by Cox regression analysis, the WPSS was the best in predicting leukemia-free survival (p<0.001, and the WPSS (p<0.001 and IPSS-R (p=0.037 were better in predicting overall survival. Conclusion: All 4 prognostic systems were successful in predicting overall survival and leukemia-free survival (p<0.001. The WPSS was found to be the best predictor for leukemia-free survival, while the WPSS and IPSS-R were found to be the best predictors for overall survival.

  14. Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

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    Babushok, Daria V; Bessler, Monica

    2015-03-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Non-hematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults.

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    Fega, K Rebecca; Abel, Gregory A; Motyckova, Gabriela; Sherman, Alexander E; DeAngelo, Daniel J; Steensma, David P; Galinsky, Ilene; Wadleigh, Martha; Stone, Richard M; Driver, Jane A

    2015-07-01

    The International Prognostic Scoring System (IPSS) is commonly used to predict survival and assign treatment for the myelodysplastic syndromes (MDS). We explored whether self-reported and readily available non-hematologic predictors of survival add independent prognostic information to the IPSS. Retrospective cohort study of consecutive MDS patients ≥age 65 who presented to Dana-Farber Cancer Institute between 2006 and 2011 and completed a baseline quality of life questionnaire. Questions corresponding to functional status and symptoms and extracted clinical-pathologic data from medical records. Kaplan-Meier and Cox proportional hazards models were used to estimate survival. One hundred fourteen patients consented and were available for analysis. Median age was 73 years, and the majority of patients were White, were male, and had a Charlson comorbidity score of <2. Few patients (24%) had an IPSS score consistent with lower-risk disease and the majority received chemotherapy. In addition to IPSS score and history of prior chemotherapy or radiation, significant univariate predictors of survival included low serum albumin, Charlson score, performance status, ability to take a long walk, and interference of physical symptoms in family life. The multivariate model that best predicted mortality included low serum albumin (HR=2.3; 95% CI: 1.06-5.14), therapy-related MDS (HR=2.1; 95% CI: 1.16-4.24), IPSS score (HR=1.7; 95% CI: 1.14-2.49), and ease taking a long walk (HR=0.44; 95% CI: 0.23-0.90). In this study of older adults with MDS, we found that low serum albumin and physical function added important prognostic information to the IPSS score. Self-reported physical function was more predictive than physician-assigned performance status. Published by Elsevier Ltd.

  16. Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform.

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    Valent, Peter; Stauder, Reinhard; Theurl, Igor; Geissler, Klaus; Sliwa, Thamer; Sperr, Wolfgang R; Bettelheim, Peter; Sill, Heinz; Pfeilstöcker, Michael

    2018-02-01

    Despite the availability of effective iron chelators, transfusion-related morbidity is still a challenge in chronically transfused patients with myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may lead to organ dysfunction or even organ failure. In addition, iron overload is associated with reduced overall survival in MDS. Areas covered: During the past 10 years, various guidelines for the management of MDS patients with iron overload have been proposed. In the present article, we provide our updated recommendations for the diagnosis, prevention and therapy of iron overload in MDS. In addition, we propose refined treatment response criteria. As in 2006 and 2007, recommendations were discussed and formulated by participants of our Austrian MDS platform in a series of meetings in 2016 and 2017. Expert commentary: Our updated recommendations should support early recognition of iron overload, optimal patient management and the measurement of clinical responses to chelation treatment in daily practice.

  17. Prognostic factors in de novo myelodysplastic syndrome in young and middle-aged people

    Directory of Open Access Journals (Sweden)

    Наталья Николаевна Климкович

    2015-01-01

    Full Text Available We spent multivariate analysis of clinical and laboratory parameters for the prediction of de-novo myelodysplastic syndromes (MDS patients aged 18-60 years. The results of clinical application of prognostic systems in MDS show that there is a large variability within individual risk groups, especially at low-risk MDS. So now hematologists conduct research aimed at identifying additional adverse risk MDS. This is done so that patients with low-risk MDS embodiments and unfavorable prognosis could benefit from early therapeutic intervention, and not only be clinician monitored until disease progression. We found that additional adverse risk factors for the development of MDS are the expression of CD95 in bone marrow ≤40 % and FLT3≥60 %. The expression level of CD95 in bone marrow cells≤40 % and FLT3≥60 % can be considered as a prognostic marker progression of MDS and time start specific therapy

  18. Utility of 5-Methylcytosine Immunohistochemical Staining to Assess Global DNA Methylation and Its Prognostic Impact in MDS Patients

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    Chandra, Dinesh; Tyagi, Seema; Singh, Jasdeep; Deka, Roopam; Manivannan, Prabhu; Mishra, Pravas; Pati, Hara Prasad; Saxena, Renu

    2017-12-29

    Background: DNA methylation plays a vital role in the pathogenesis of the myelodysplastic syndrome (MDS), a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders. It is reported to be an independent prognostic factor affecting overall survival (OS). Our aim was to analyze the role of global DNA methylation using an anti-5-methylcytosine (5-MC) antibody by immunohistochemistry (IHC) of bone marrow biopsy (BM Bx) specimens in MDS patients, assessing correlations with various clinical and biological prognostic factors. Material and methods: A total of 59 MDS cases, classified as per the World Health Organization (WHO) 2008 guidelines, were evaluated over a period of 4 years. Clinical data were retrieved from departmental case records and anti-5-MC expression was analyzed with formalin fixed paraffin embedded sections of BM Bx specimens of MDS patients and controls. Results: The median age at diagnosis was 52 years (15-85years). Patients were categorized into low risk (59%) and high risk (41%) according to International Prognostic Scoring System (IPSS). The median follow-up time was 10 months (1 to 37 months). We generated a methylation score (M-score) using anti-5-MC and with the derived cut-off of 30.5 from the receiver operator curve (ROC), there was a significant difference between the two groups in the percentage of BM blasts (p=0.01), WHO sub-type (p=0.01), IPSS (p=0.004), progression to AML (p=0.04) on univariate analysis. Interestingly, patients showing a high M-score (M-score ≥ 30.5) demonstrated a significantly shorter OS and progression to AML. However, on multivariate analysis, only BM blasts (p=0.01) and IPSS (p=0.02) remained independent variables for progression to AML and OS respectively. Conclusion: Immunostaining with anti-5-MC antibody with BM Bx samples is a simple and cost effective technique to detect global methylation, a powerful tool to predict overall survival in patients with MDS. Creative Commons Attribution License

  19. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: A subset analysis from the MDS-004 study

    NARCIS (Netherlands)

    A. Giagounidis (Aristoteles); G.J. Mufti (Ghulam); M. Mittelman (Moshe); G. Sanz (Guillermo); U. Platzbecker (Uwe); P. Muus (P.); D. Selleslag; O. Beyne-Rauzy (Odile); P.A.W. te Boekhorst (Peter); C. del Cañizo (Consuelo); A. Guerci-Bresler (Agnes); L. Nilsson (Lars); M. Lübbert (Michael); B. Quesnel (Bruno); A. Ganser (Arnold); D. Bowen (David); B. Schlegelberger (Brigitte); G. Göhring (Gudrun); T. Fu (Tommy); B. Benettaib (Bouchra); E. Hellström-Lindberg (Eva); P. Fenaux (Pierre)

    2014-01-01

    textabstractObjective: A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods: Patients received

  20. Myelodysplastic Syndrome, Unclassifiable (MDS-U) With 1% Blasts Is a Distinct Subgroup of MDS-U With a Poor Prognosis.

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    Margolskee, Elizabeth; Hasserjian, Robert P; Hassane, Duane; Tam, Wayne; Mathew, Susan; Ok, Chi Young; Wang, Sa A; Oak, Jean; Arber, Daniel A; Orazi, Attilio

    2017-07-01

    Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. MDS-U cases were reviewed at four major academic institutions. Targeted next-generation sequencing for genes implicated in myeloid neoplasms was performed in a subset of cases. Twenty-seven patients were identified (six MDS-U BL, 13 MDS-U Pan, and eight MDS-U CG). Clonal cytogenetic abnormalities were found in six of six, seven of 13, and eight of eight cases in MDS-U BL, Pan, and CG, respectively (P > .05). Overall, four of six patients with MDS-U BL progressed to acute myeloid leukemia; no MDS-U Pan or CG patients did. The rates of progression-free survival and mortality (overall survival) were significantly higher in MDS-U BL compared with Pan and CG (P MDS-U BL is a distinct subset of MDS-U with a poor prognosis, while MDS-U Pan and CG are relatively indolent. Evaluation of peripheral blood smears in patients with MDS is essential for accurate classification and prognosis. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. [Cytogenetics of myelodysplastic syndromes and its impact as prognostic factor].

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    Borjas-Gutiérrez, César; Domínguez-Cruz, Martín Daniel; González-García, Juan Ramón

    2017-01-01

    Myelodysplastic syndromes (MDS) are a group of disorders of the hematopoietic stem cell. They are characterized by cytopenia(s), dysplasia of one or more cell lines, ineffective hematopoiesis, and an increased risk for developing acute myelogenous leukemia. The classification of MDS has been complicated due to the great heterogeneity in clinical phenotype as well as in the morphological and cytogenetic characteristics. The prognostic value of cytogenetic abnormalities in MDS has been analyzed in multicenter studies. This approach raised the development of the revised International Prognostic Scoring System (IPSS-R), which analyzes five prognostic variables, among which the cytogenetic study stands out. According to the cytogenetic findings, a classification of MDS in five subgroups was developed. Knowledge of the cytogenetic abnormalities has led to the study of genes involved in various chromosomal rearrangements. Moreover, DNA sequencing has helped to identify mutations in approximately 50 genes related to signal transduction, DNA methylation, transcriptional regulation, and RNA splicing. Therefore, the cytogenetic study should be used to improve the classification and therapeutic management of MDS. This approach will be an essential tool for the development of targeted therapy protocols.

  2. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study.

    Science.gov (United States)

    Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry

    2016-08-19

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated. The Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients. The Connect MDS/AML Disease

  3. Improved risk stratification by the integration of the revised international prognostic scoring system with the myelodysplastic syndromes comorbidity index.

    Science.gov (United States)

    van Spronsen, M F; Ossenkoppele, G J; Holman, R; van de Loosdrecht, A A

    2014-12-01

    Myelodysplastic syndromes (MDS) comprise bone marrow failure diseases with a diverse clinical outcome. For improved risk stratification, the International Prognostic Scoring System (IPSS) has recently been revised (IPSS-R). This single-centre study aimed to validate the IPSS-R and to evaluate prior prognostic scoring systems for MDS. We retrospectively analysed 363 patients diagnosed with MDS according to the FAB criteria between 2000 and 2012. The IPSS, MD Anderson Risk Model Score (MDAS), World Health Organisation (WHO)-classification based Prognostic Scoring System (WPSS), refined WPSS (WPSS-R), IPSS-R and MDS-Comorbidity Index (MDS-CI) were applied to 222 patients considered with primary MDS following the WHO criteria and their prognostic power was investigated. According to the IPSS-R, 18 (8%), 81 (37%), 50 (23%), 43 (19%) and 30 (13%) patients were classified as very low, low, intermediate, high and very high risk with, respectively, a median overall survival of 96 (95% Confidence interval (CI) not reached), 49 (95% CI 34-64), 22 (95% CI 0-49), 19 (95% CI 11-27) and 10 (95% CI 6-13) months (pMDS-CI refined the risk stratification of MDS patients stratified according to the IPSS-R. In conclusion, accounting for the disease status by means of the IPSS-R and comorbidity through the MDS-CI considerably improves the prognostic assessment in MDS patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...

  5. Unique cytogenetic findings confirmed by FISH in a rare case of infant MDS with major prognostic implications

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, M.J.; Haag, M.M.; Dumont, D.P. [Univ. of South Florida, Tampa, FL (United States)] [and others

    1994-09-01

    An extremely rare finding in the young, the myelodysplastic syndrome (MDS) refractory anemia with excess blasts (RAEB), is distinguished by blood cytopenia, trilineage dyspoiesis and an increase in peripheral and bone marrow blasts. A 3-year-old male presented with arm pain of one week duration followed by progressive bruising, high fever and severe headaches. Bone marrow pathology revealed dysmyelopoietic granulocytic hyperplasia, marked reduction in megakaryocytes and increased blastosis suggestive of RAEB. Peripheral blood smear confirmed leukoerythroblastic anemia, reticulocytopenia and thyrombocytopenia. Cytogenetic bone marrow evaluation showed the majority of cells with ring (11), monosomies No. 17 and No. 20 and a derivative No. 12 chromosome. Due to the structural complexity and diagnostic and prognostic implications of accurate interpretation, analysis was confirmed using FISH COATASOME probes No. 11, No. 12 and No. 20 (Oncor, Inc.). The rearranged chromosome comprised chromosomes 12 and 20. Breakpoints in No. 12 were at p13 and q24.3. The breakpoint in chromosome 20 at q11.2 resulted in attachment of the distal 20q11.2 fragment to 12q and the centromere and p arm to 12p. C-banding confirmed two centromeres. Progression to ANLL is observed in 15-30% of patients with MDS. Distinction between RAEB and ANLL challenges diagnosis and patient management. Clonal chromosomal abnormalities due to RAEB and nonrandom ANLL changes also show considerable overlap, emphasizing their basic pathobiological similarity. However, r(11) has been described in ANLL and although the structurally rearranged No. 12 is believed to be a unique finding, the breakpoints were considered diagnostically significant. The presence of unusual cytogenetic findings may herald progression of MDS to acute leukemia before morphological classification is evident, emphasing the importance of clarifying structural abnormalities that may provide powerful evidence for clinical management.

  6. Clinical Features and Outcomes of 666 Cases with Therapy-Related Myelodysplastic Syndrome (t-MDS).

    Science.gov (United States)

    El-Fattah, Mohamed Abd

    2018-01-01

    Therapy-related myelodysplastic syndrome (t-MDS) is a serious complication of chemoradiotherapy for primary diseases. This cohort was aimed to determine the clinical features and outcomes of t-MDS in comparison with de novo MDS. I retrieved data of 666 cases with t-MDS, and 29,703 cases with de novo MDS diagnosed between 2001 and 2012 from the database of U.S. National Cancer Institute. Survival curves were estimated, and Cox proportional hazards model was constructed. Compared with patients with de novo MDS, patients with t-MDS tended to be young (median age; 65 vs. 76 years, p  MDS than de novo MDS (17.2 months and 22% vs. 31 months and 32%, respectively, p  MDS cases, with a median follow-up of 16 months (range 1-143 months), 521 cases (78.2%) had died. Of which, 78 (15%) cases had died from acute myeloid leukemia, and 66 (12.7%) cases had died from solid cancers. Of the total 66 cases died from solid cancers; 19 cases (28.8%) died from cancer of lung/bronchus, 11 cases (16.7%) breast cancers, and 10 cases (15.2%) ovarian cancer. In a multivariate analysis adjusted for clinical features, calendar period and radiotherapy, the hazard of mortality was significantly low in de novo MDS compared with t-MDS (hazard ratio 0.59; p  MDS is a distinct entity of MDS in terms of clinical characteristics and prognosis.

  7. Prognostic impact of a suboptimal number of analyzed metaphases in normal karyotype lower-risk MDS.

    Science.gov (United States)

    de Swart, Louise; Smith, Alex; Haase, Detlef; Fenaux, Pierre; Symeonidis, Argiris; Cermak, Jaroslav; Sanz, Guillermo; Stauder, Reinhard; Mittelman, Moshe; Hellström-Lindberg, Eva; Malcovati, Luca; Langemeijer, Saskia; Skov-Holm, Mette; Mądry, Krzysztof; Germing, Ulrich; Almeida, Antonio Medina; Tatic, Aurelia; Savic, Aleksandar; Šimec, Njetočka Gredelj; van Marrewijk, Corine; Guerci-Bresler, Agnes; Sanhes, Laurence; Luño, Elisa; Culligan, Dominic; Beyne-Rauzy, Odile; Burgstaller, Sonja; Blijlevens, Nicole; Bowen, David; de Witte, Theo

    2018-04-01

    Conventional karyotype is one of the most relevant prognostic factors in MDS. However, about 50% of patients with MDS have a normal karyotype. Usually, 20-25 normal metaphases (nMP) are considered to be optimal to exclude small abnormal clones which might be associated with poor prognosis. This study evaluated the impact of examining a suboptimal number of metaphases in patients recruited to the EUMDS Registry with low and intermediate-1 risk according to IPSS. Only 179/1049 (17%) of patients with a normal karyotype had a suboptimal number of nMP, defined as less than 20 metaphases analyzed. The outcome (overall survival and progression-free survival) of patients with suboptimal nMP was not inferior to those with higher numbers of analyzed MP both in univariate and multivariate analyses. For patients with an abnormal karyotype, 224/649 (35%) had a suboptimal number of MP assessed, but this did not impact on outcome. For patients with a normal karyotype and suboptimal numbers of analyzable metaphases standard evaluation might be acceptable for general practice, but we recommend additional FISH-analyses or molecular techniques, especially in candidates for intensive interventions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Deferasirox for transfusion-dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial).

    Science.gov (United States)

    Angelucci, Emanuele; Santini, Valeria; Di Tucci, Anna Angela; Quaresmini, Giulia; Finelli, Carlo; Volpe, Antonio; Quarta, Giovanni; Rivellini, Flavia; Sanpaolo, Grazia; Cilloni, Daniela; Salvi, Flavia; Caocci, Giovanni; Molteni, Alfredo; Vallisa, Daniele; Voso, Maria Teresa; Fenu, Susanna; Borin, Lorenza; Latte, Giancarlo; Alimena, Giuliana; Storti, Sergio; Piciocchi, Alfonso; Fazi, Paola; Vignetti, Marco; Tura, Sante

    2014-06-01

    In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted. The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined. Of 159 participants enrolled from 37 Italian centers, 152 received ≥1 dose of deferasirox (initiated at 10-20 mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966 ng/mL to 1475 ng/mL (P Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independence. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): Characteristics of refined MDS types.

    Science.gov (United States)

    Strupp, Corinna; Nachtkamp, Kathrin; Hildebrandt, Barbara; Giagounidis, Aristoteles; Haas, Rainer; Gattermann, Norbert; Bennett, John M; Aul, Carlo; Germing, Ulrich

    2017-06-01

    Based on centrally diagnosed 3528 patients in the Düsseldorf registry, we validated the new proposals for the classification of the MDS by the WHO working group: 256 patients were diagnosed as MDSSLD (7,3%), 978 MDSMLD (27,7%), 227 MDS RS SLD (6,4%); 321 MDS RS MLD (9,1%), 159 MDS del(5q) (4,5%), 481 MDSEB 1 (13,6%), 620 MDSEB 2 (17,6%), and 148 MDS-U (4,2%). 352 patients (16,9% of the non blastic types) changed the category, mainly moving from RCMD to MDS RS MLD, RCUD and RCMD to MDS del(5q). Median survival times of the refined groups differed from more than 60 months in the MDSSLD (RS) groups, 37 months in the MDSMLD (RS) groups, 79 months of the MDS del(5q) group and 21 and 11 months in the MDSEB 1 and 2 groups, respectively. The difference between the groups with regard to the risk of AML evolution was also impressing. No major changes were made with regard to the MDS-U categories. In summary, the proposals of the WHO group for the classification of MDS are thoughtful, taking into account biologic parameters of the diseases, a more precise wording, to some extend pragmatic and feasible. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Clinical and biological significance of isolated Y chromosome loss in myelodysplastic syndromes and chronic myelomonocytic leukemia. A report from the Spanish MDS Group.

    Science.gov (United States)

    Nomdedeu, Meritxell; Pereira, Arturo; Calvo, Xavier; Colomer, Joan; Sole, Francesc; Arias, Amparo; Gomez, Candida; Luño, Elisa; Cervera, Jose; Arnan, Montserrat; Pomares, Helena; Ramos, Fernando; Oiartzabal, Itziar; Espinet, Blanca; Pedro, Carme; Arrizabalaga, Beatriz; Blanco, María Laura; Tormo, Mar; Hernandez-Rivas, Jesus Maria; Díez-Campelo, María; Ortega, Margarita; Valcárcel, David; Cedena, Maria-Teresa; Collado, Rosa; Grau, Javier; Granada, Isabel; Sanz, Guillermo; Campo, Elias; Esteve, Jordi; Costa, Dolors

    2017-12-01

    Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML). -Y was identified in 177 patients (4.9%). Compared with the 2246 male patients with normal karyotype, -Y group showed a reduced risk of leukemic transformation that did not translate into a survival advantage. The overall survival and the risk of leukemic transformation were not influenced by the percentage of metaphases with -Y. The -Y group was not enriched in patients with minor morphologic traits of dysplasia, suggesting that the better outcome in the -Y group cannot be explained by enrichment in cases misdiagnosed as MDS. In conclusion, our results support the current recommendation of classifying patients with -Y within the very good risk category of the IPSS-R for MDS and rule out a selection bias as a possible explanation of this better outcome. An analysis of the molecular basis of MDS with isolated -Y would be of interest as it may provide a biological basis of protection against progression to acute leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. [Clinical significance of WHO classification and MDS 2000 classification in myelodysplastic syndromes].

    Science.gov (United States)

    Akiba, M; Matsuda, A; Misumi, M; Yagasaki, F; Bessho, M

    2001-12-01

    Excluding chronic myelomonocytic leukemia, a total of 92 consecutive patients with myelodysplastic syndrome showing less than 20% blasts in the bone marrow were analyzed. We evaluated the clinical significance of the WHO and MDS 2000 classifications by reviewing each MDS patient according to the classification. The WHO criteria classified the MDS patients into 36 with RA, 22 with RCMD and 33 with RAEB, whereas according to the MDS 2000 criteria there were 19 RAEB-I patients and 15 RAEB-II patients. Based on the WHO classification, the RCMD patients had higher platelet counts and percentages of blasts among BM cells than the RA patients (P = 0.0018, P = 0.0001). Twenty percent of the RA patients, 44.8% of the RCMD patients, and 70.8% of the RAEB patients had cytogenetic abnormalities. Among them, the poor karyotype was present in 6.7% of the RA patients, 21.0% of the RCMD patients and 41.6% of the RAEB patients. The rate of acute leukemia death was 14.3% in the RA patients, 67.7% in the RAEB patients and 50.0% in the RCMD patients. Analysis of survival times revealed significant differences between RA and RCMD patients (P = 0.0482). The clinical features of RCMD patients were intermediate between those of RAEB and RA patients. There was no difference between the clinical features of the RAEB-I and RAEB-II patients in the MDS 2000 classification.

  12. A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia.

    Science.gov (United States)

    Navada, Shyamala C; Fruchtman, Steven M; Odchimar-Reissig, Rosalie; Demakos, Erin P; Petrone, Michael E; Zbyszewski, Patrick S; Holland, James F; Silverman, Lewis R

    2018-01-01

    This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m 2 /day in 14-day cycles. Initial dose escalation followed a Fibonacci scheme, followed by recommended phase 2 dose confirmation in an expanded cohort. Rigosertib was well tolerated for up to 23 cycles, with no treatment-related deaths and 18% of patients with related serious adverse events (AEs). Common AEs were fatigue, diarrhea, pyrexia, dyspnea, insomnia, and anemia. Rigosertib exhibited biologic activity, with reduction or stabilization of bone marrow blasts and improved peripheral blood counts in a subset of patients. Ten of 19 evaluable patients (53%) demonstrated bone marrow/peripheral blood responses (n=4 MDS, n=1 AML) or stable disease (n=3 MDS, n=2 AML). Median survival was 15.7 and 2.0 months for responders and non-responders, respectively. Additional studies of rigosertib are ongoing in higher-risk MDS (NCT00854646). Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Childhood MDS

    Science.gov (United States)

    ... Myeloma Awareness Month Help Us Find a Cure Childhood MDS Childhood MDS Print Glossary To access information about coping ... be the same treatment approach for the disorder. Childhood MDS Subtypes Subtypes of primary childhood MDS are ...

  14. Allogeneic hematopoietic stem cell transplant in adult patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes.

    Science.gov (United States)

    Sharma, Prashant; Shinde, Shivani S; Damlaj, Moussab; Hefazi Rorghabeh, Mehrdad; Hashmi, Shahrukh K; Litzow, Mark R; Hogan, William J; Gangat, Naseema; Elliott, Michelle A; Al-Kali, Aref; Tefferi, Ayalew; Patnaik, Mrinal M

    2017-04-01

    MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT-comorbidity index (HSCT-CI >3 versus ≤3; p = 0.015) and splenomegaly (p = 0.006) predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p = 0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT within 1-year of diagnosis was associated with improved OS (p = 0.045). In MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and 14%, respectively.

  15. Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity: results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS).

    Science.gov (United States)

    Wermke, Martin; Schuster, Claudia; Nolte, Florian; Al-Ali, Haifa-Kathrin; Kiewe, Philipp; Schönefeldt, Claudia; Jakob, Christiane; von Bonin, Malte; Hentschel, Leopold; Klut, Ina-Maria; Ehninger, Gerhard; Bornhäuser, Martin; Baretton, Gustavo; Germing, Ulrich; Herbst, Regina; Haase, Detelef; Hofmann, Wolf K; Platzbecker, Uwe

    2016-12-01

    The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower- and 11 higher-risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival (OS) was not reached in the lower-risk group and 296 days in the higher-risk group. We observed a significant decline of bone marrow (BM) vascularisation (P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro-inflammatory T-helper-cell subsets within the peripheral blood or BM. We conclude that mTOR-modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients. © 2016 John Wiley & Sons Ltd.

  16. MDS classification is improving in an era of the WHO 2016 criteria of MDS: A population-based analysis among 9159 MDS patients diagnosed in the Netherlands.

    Science.gov (United States)

    Dinmohamed, Avinash G; Visser, Otto; Posthuma, Eduardus F M; Huijgens, Peter C; Sonneveld, Pieter; van de Loosdrecht, Arjan A; Jongen-Lavrencic, Mojca

    2017-10-01

    Morphologic and cytogenetic assessments are required to characterize diagnostic and prognostic features of myelodysplastic syndromes (MDS). We assessed whether these assessments were performed among newly diagnosed MDS patients in the Netherlands. MDS cases were retrieved from the nationwide Netherlands Cancer Registry (N=9159; period 2001-2014) and the regional PHAROS MDS registry (N=676; period 2008-2011). The proportion of unclassified MDS decreased from 58% in 2001 to 13% in 2014. Data from the more detailed PHAROS registry revealed that the degree of bone marrow dysplasia was only reported in ∼30% of all evaluable bone marrow aspirates. Further, the International Prognostic Scoring System was undetermined in 55% of patients, primarily owing to unperformed cytogenetics in 46% of patients. The classification of MDS is improving in the Netherlands. Nevertheless, particular diagnostic and prognostic procedures that are essential for the diagnosis and subsequent treatment decision-making of MDS were not fully utilized in particular patient subsets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. MDS: Recent progress in molecular pathogenesis and clinical aspects.

    Science.gov (United States)

    Harada, Hironori

    2017-01-01

    Myelodysplastic syndromes (MDS) are defined as hematopoietic stem cell disorders caused by various gene abnormalities. Recent analysis using next generation sequencing has provided great progress in identifying relationships between gene mutations and clinical phenotypes of MDS. It is estimated that one or more gene mutations occur in greater than 90% of MDS patients. More than 50 gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins, and components of the cohesion complex participate in the pathogenesis of MDS. The sequential accumulation of additional cooperating mutations drives disease evolution from clonal hematopoiesis of indeterminate potential (CHIP) to symptomatic MDS and from MDS to acute myelogenous leukemia (AML). Mutations in RNA splicing and DNA methylation occur early and are considered founding mutations, whereas others that occur later are regarded as subclonal mutations. RUNX1 mutations are more likely to be subclonal; however, they apparently play a pivotal role in familial MDS. In addition, large alterations of chromosomes are involved in the pathogenesis of MDS. 5q- syndrome, which leads to haploinsufficiency of the located genes, has consistent clinical features. Understanding gene abnormalities of MDS patients can provide clinical information, including diagnosis, prognostic score, and prediction of response to therapy.

  18. Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Corrales-Yepez, Maria; Kharfan-Dabaja, Mohamed A; Al Ali, Najla H; Padron, Eric; Rollison, Dana E; Pinilla-Ibarz, Javier; Zhang, Ling; Epling-Burnette, Pearlie K; Lancet, Jeffrey E; List, Alan F

    2012-11-01

    We hypothesized that hypoalbuminemia is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). We analyzed records of 767 patients treated at Moffitt Cancer Center between January 2001 and December 2009 to evaluate the relationship between serum albumin (SA) at the time of presentation and overall survival (OS). Patients (median age of 69 years) were stratified into three groups based on SA concentration (≤3.5, 3.6-4.0, and >4.0 g/dL). Two-thirds of the patients had low or intermediate-1 International Prognostic Scoring System (IPSS)-based risk for MDS. Median OS by SA concentration of ≤3.5, 3.6-4.0, and >4.0 g/dL was 11, 23, and 34 months, respectively (P < 0.005), whereas rate of acute myeloid leukemia progression was highest in patients with low SA (≤3.5 g/dL). The SA level offered prognostic discrimination for outcomes within the lower and higher IPSS risk groups, as well as with the MD Anderson risk model. In multivariable analysis, SA was a significant independent co-variate for OS after adjustment for IPSS, age, serum ferritin, and transfusion dependence (hazard ratio = 0.8; 95% CI 0.6-0.9; P = 0.004). Our findings indicate that hypoalbuminemia is an independent prognostic biomarker that may serve as a surrogate representative of disease biology or comorbidities in patients with MDS. Copyright © 2012 Wiley Periodicals, Inc.

  19. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia.

    Science.gov (United States)

    Garcia-Manero, Guillermo; Almeida, Antonio; Giagounidis, Aristoteles; Platzbecker, Uwe; Garcia, Regina; Voso, Maria Teresa; Larsen, Stephen R; Valcarcel, David; Silverman, Lewis R; Skikne, Barry; Santini, Valeria

    2016-01-01

    CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1-risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described. Patients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization. This study will provide data

  20. The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts

    International Nuclear Information System (INIS)

    Kang, Min-Gu; Kim, Hye-Ran; Seo, Bo-Young; Lee, Jun Hyung; Choi, Seok-Yong; Kim, Soo-Hyun; Shin, Jong-Hee; Suh, Soon-Pal; Ahn, Jae-Sook; Shin, Myung-Geun

    2015-01-01

    Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083). Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS. The online version of this article (doi:10.1186/s12885-015-1493-5) contains supplementary material, which is available to authorized users

  1. Aplastic Anemia & MDS International Foundation

    Science.gov (United States)

    ... In Treatment at NIH "The Aplastic Anemia and MDS International Foundation is helping patients like me cope with bone marrow failure disease." Diseases Aplastic Anemia Myelodysplastic Syndromes (MDS) Paroxysmal Nocturnal Hemoglobinuria (PNH) Related Diseases Treatments ...

  2. Multiplex ligation-dependent probe amplification assay identifies additional copy number changes compared with R-band karyotype and provide more accuracy prognostic information in myelodysplastic syndromes.

    Science.gov (United States)

    Wang, Jingya; Ai, Xiaofei; Qin, Tiejun; Xu, Zefeng; Zhang, Yue; Liu, Jinqin; Li, Bing; Fang, Liwei; Zhang, Hongli; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang; Cai, Wenyu; Ru, Kun; Jia, Yujiao; Huang, Gang; Xiao, Zhijian

    2017-01-03

    Cytogenetic analysis provides important diagnostic and prognostic information for patients with Myelodysplastic syndromes (MDS) and plays an essential role in the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R). Multiplex ligation-dependent probe amplification (MLPA) assay is a recently developed technique to identify targeted cytogenetic aberrations in MDS patients. In the present study, we evaluated the results obtained using an MLPA assay in 437 patients with MDS to determine the efficacy of MLPA analysis. Using R-banding karyotyping, 45% (197/437) of MDS patients had chromosomal abnormalities, whereas MLPA analysis detected that 35% (153/437) of MDS cases contained at least one copy-number variations (CNVs) .2/5 individuals (40%) with R-band karyotype failures had trisomy 8 detected using only MLPA. Clonal cytogenetic abnormalities were detected in 20/235 (8.5%) MDS patients with a normal R-band karyotype, and 12/20 (60%) of those patients were reclassified into a higher-risk IPSS-R prognostic category. When sequencing and cytogenetics were combined, the fraction of patients with MDS-related oncogenic lesions increased to 87.3% (233/267 cases). MLPA analysis determined that the median OS of patients with a normal karyotype (n=218) was 65 months compared with 27 months in cases with an aberrant karyotype (P=0.002) in 240 patients with normal or failed karyotypes by R-banding karyotyping. The high-resolution MPLA assay is an efficient and reliable method that can be used in conjunction with R-band karyotyping to detect chromosomal abnormalities in patients with suspected MDS. MLPA may also provide more accurate prognostic information.

  3. Impact Of Mutation-derived Antigens In Immune Recognition Of Hematological Malignancies, Specifically Myeloid Dysplastic Syndromes (MDS)

    DEFF Research Database (Denmark)

    Saini, Sunil Kumar; Dorfmüller, S.; Bjerregaard, Anne-Mette

    2016-01-01

    Mutation-derived neoepitopes have been suggested as a major component for immune recognition of solid tumors with a high mutational load, e.g. Melanoma and Non-Small-Cell Lung Cancer (NSCLC). Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by increasing...

  4. Impact Of Mutation-derived Antigens In Immune Recognition Of Hematological Malignancies, Specifically Myeloid Dysplastic Syndromes (MDS)

    DEFF Research Database (Denmark)

    Saini, Sunil Kumar; Dorfmüller, S.; Bjerregaard, Anne-Mette

    2016-01-01

    Mutation-derived neoepitopes have been suggested as a major component for immune recognition of solid tumors with a high mutational load, e.g. Melanoma and Non-Small-Cell Lung Cancer (NSCLC). Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by increasing...... to the generation of tumor-specific neoepitopes....

  5. Usefulness and prognostic impact on survival of WHO reclassification in FAB low risk myelodyplastic syndromes.

    Science.gov (United States)

    Breccia, Massimo; Carmosino, Ida; Biondo, Francesca; Mancini, Marco; Russo, Eleonora; Latagliata, Roberto; Alimena, Giuliana

    2006-02-01

    In 1999, WHO proposed a revised classification for myelodysplastic syndromes (MDS). According to this system, FAB low risk MDS (RA and RARS) were defined as such when the presence of dysplastic features was only restricted to the erythroid lineage, and new categories, refractory cytopenia with multilineage dysplasia (RCMD) and refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS), were added. In a retrospective analysis of 240 consecutive patients diagnosed at our institution as having FAB RA and RARS, we reclassified the disease following the WHO criteria and we found that 179/214 patients (84%) still remained in the RA category, while 35/214 (16%) moved to RCMD. Moreover, 17/26 patients (65%) maintained the RARS diagnosis, whereas 9/26 (35%) were re-classified as RCMD-RS. We detected differences among the WHO subgroups as to age and sex distribution as well as to median survival observed by stratifying patients according to different prognostic scoring systems. Furthermore we confirmed the usefulness of WHO segregation with regard to its predictive value for evolution into acute leukaemia. Our study provides evidence that WHO classification may have prognostic impact on MDS subgroups which are usually categorized by FAB as having a favourable outcome.

  6. A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the "MDS thermometer".

    Science.gov (United States)

    Aires, Ana; Teixeira, Maria Dos Anjos; Lau, Catarina; Moreira, Cláudia; Spínola, Ana; Mota, Alexandra; Freitas, Inês; Coutinho, Jorge; Lima, Margarida

    2018-01-01

    Immunophenotypic analysis of the bone marrow (BM) cells has proven to be helpful in the diagnosis of Myelodysplastic Syndromes (MDS). However, the usefulness of flow cytometry (FCM) for the detection of myelodysplasia in the peripheral blood (PB) still needs to be investigated. The aim of this pilot study was to evaluate the value of FCM-based PB neutrophil and monocyte immunophenotyping for the diagnosis of lower risk MDS (LR-MDS). We evaluated by 8-color FCM the expression of multiple cell surface molecules (CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD34, CD45, CD56, CD64 and HLA-DR) in PB neutrophils and monocytes from a series of 14 adult LR-MDS patients versus 14 normal individuals. Peripheral blood neutrophils from patients with LR-MDS frequently had low forward scatter (FSC) and side scatter (SSC) values and low levels of CD11b, CD11c, CD10, CD16, CD13 and CD45 expression, in that order, as compared to normal neutrophils. In addition, patients with LR-MDS commonly display a higher fraction of CD14 + CD56 + and a lower fraction of CD14 + CD16 + monocytes in the PB. Based on these results, we proposed an immunophenotyping score based on which PB samples from patients with LR-MDS could be distinguished from normal PB samples with a sensitivity 93% and a specificity of 100%. In addition, we used this score to construct the MDS Thermometer, a screening tool for detection and monitoring of MDS in the PB in clinical practice. Peripheral blood neutrophil and monocyte immunophenotyping provide useful information for the diagnosis of LR-MDS, as a complement to cytomorphology. If validated by subsequent studies in larger series of MDS patients and extended to non-MDS patients with cytopenias, our findings may improve the diagnostic assessment and avoid invasive procedures in selected groups of MDS patients.

  7. The 2016 revised World Health Organization definition of 'myelodysplastic syndrome with isolated del(5q)'; prognostic implications of single versus double cytogenetic abnormalities.

    Science.gov (United States)

    Gurney, Mark; Patnaik, Mrinal M; Hanson, Curtis A; Litzow, Mark R; Al-Kali, Aref; Ketterling, Rhett P; Tefferi, Ayalew; Gangat, Naseema

    2017-07-01

    The definition of the myelodysplastic syndrome (MDS) subtype 'MDS with isolated del(5q)' was expanded to include cases with one additional non-chromosome 7 based cytogenetic abnormality in the 2016 revised World Health Organization classification. This study applied the revised definition to a large primary MDS cohort, and evaluated the prognostic impact of the additional cytogenetic abnormality. Seventy-two of 1067 patients (7%) met the 'MDS with isolated del(5q)' criteria, 11 (1%) of whom had an additional cytogenetic abnormality. There was no survival difference between patients in whom del(5q) occurred alone, compared to those with one additional cytogenetic abnormality (P = 0·52). © 2017 John Wiley & Sons Ltd.

  8. Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients.

    Science.gov (United States)

    Díez Campelo, M; Sánchez-Barba, M; de Soria, V Gómez-García; Martino, R; Sanz, G; Insunza, A; Bernal, T; Duarte, R; Amigo, M L; Xicoy, B; Tormo, M; Iniesta, F; Bailén, A; Benlloch, L; Córdoba, I; López-Villar, O; Del Cañizo, M C

    2014-10-01

    Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making.

    Science.gov (United States)

    Malcovati, Luca; Porta, Matteo Giovanni Della; Pascutto, Cristiana; Invernizzi, Rosangela; Boni, Marina; Travaglino, Erica; Passamonti, Francesco; Arcaini, Luca; Maffioli, Margherita; Bernasconi, Paolo; Lazzarino, Mario; Cazzola, Mario

    2005-10-20

    The aim of this study was to evaluate the prognostic value of the WHO proposal, to assess the role of the main prognostic factors in myelodysplastic syndromes (MDSs) classified into WHO subgroups, and to estimate mortality (standardized mortality ratio [SMR]) and life expectancy in these groups as a basis for clinical decision making. Four hundred sixty-seven patients who were diagnosed as having de novo MDS at the Division of Hematology, University of Pavia (Pavia, Italy), between 1992 and 2002, were evaluated retrospectively for clinical and hematologic features at diagnosis, overall survival (OS), and progression to leukemia (leukemia-free survival). Significant differences in survival were noted between patients with refractory anemia (RA), refractory cytopenia with multilineage dysplasia, RA with excess blasts, type 1 (RAEB-1), and RAEB-2. The effect of demographic factors on OS was observed in MDS patients without excess blasts (age, P = .001; sex, P = .006), as in the general population. The mortality of RA patients 70 years or older did not differ significantly from that of the general population (SMR, 1.62; P = .06). Cytogenetics was the only International Prognostic Scoring System variable showing a prognostic value in MDS classified into WHO subgroups. Transfusion-dependent patients had a significantly shorter survival than patients who did not require transfusions (P WHO classification of MDSs has a relevant prognostic value. This classification, along with cytogenetics, might be useful in decisions regarding transplantation. MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable.

  10. Prognostic value of trisomy 8 as a single anomaly and the influence of additional cytogenetic aberrations in primary myelodysplastic syndromes.

    Science.gov (United States)

    Saumell, Sílvia; Florensa, Lourdes; Luño, Elisa; Sanzo, Carmen; Cañizo, Consuelo; Hernández, Jesus M; Cervera, José; Gallart, Miguel A; Carbonell, Félix; Collado, Rosa; Arenillas, Leonor; Pedro, Carme; Bargay, Joan; Nomdedeu, Benet; Xicoy, Blanca; Vallespí, Teresa; Raya, José M; Belloch, Luis; Sanz, Guillermo F; Solé, Francesc

    2012-11-01

    Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group. © 2012 Blackwell Publishing Ltd.

  11. Cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC in myelodysplastic syndrome (MDS

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria-Hernández

    2017-06-01

    Full Text Available ABSTRACTIntroductionMyelodysplastic syndrome (MDS comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML. Therapeutic benefit should include overall survival increase (OS, hematological improvement, transfusion dependence and time to progression to AML decrease.ObjectiveAssess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC plus best supportive care (BSC for the treatment of adult patients with intermediate-2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA were conducted by simultaneously sampling from estimated probability distributions of model parameters.ResultsOverall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG. PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay.ConclusionsCompared with LDC, azacitidine represents a cost-effective treatment alternative in patients

  12. Prognostic factors in Guillain-Barre syndrome

    Directory of Open Access Journals (Sweden)

    Semra Mungan

    2014-12-01

    Full Text Available Objective: Guillain–Barre syndrome (GBS is an immune-mediated disorder of peripheral nerves resulting as acute inflammatory demyelinating polyradiculoneuropathy. GBS has a heterogeneous clinical course and laboratory findings. Acute onset and progressive course, and is usually associated with a good prognosis but some forms have a poor prognosis. Factors that can affect the prognosis of GBS have been investigated in several studies. Assessment of poor prognostic factors of GBS plays a vital role in the management and monitorization of patients. Methods: In this retrospective study of patients admitted to the acute phase of GBS removing clinical and laboratory profiles and was planned to investigate the prognostic factors. Results: Totally 23 patients (Female/male: 16/7 were recruited. Mean age was 47 (range: 17-70 years. Statistically significant poor prognostic factors were advanced age (p=0.042, erythrocyte sedimentation rate (p=0.027 and serum albumin level (p=0.007. Conclusion: Advanced age, increased ESR and decreased albumin levels were found as poor prognostic factors in GBS.

  13. Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact.

    Science.gov (United States)

    Bacher, Ulrike; Haferlach, Torsten; Schnittger, Susanne; Zenger, Melanie; Meggendorfer, Manja; Jeromin, Sabine; Roller, Andreas; Grossmann, Vera; Krauth, Maria-Theresa; Alpermann, Tamara; Kern, Wolfgang; Haferlach, Claudia

    2014-03-01

    In patients with myelodysplastic syndromes (MDS), sole 20q deletion [del(20q)] is a recurrent favourable abnormality. We studied additional molecular and cytogenetic lesions and their prognostic impact in 305 MDS patients with del(20q) (229 males/76 females; 29-90 years). All patients were investigated by cytomorphology and chromosome banding analysis (CBA), subsets by fluorescence in situ hybridization, molecular mutation screening, and array comparative genomic hybridization (aCGH). By aCGH (n = 30), the minimal common deleted region (CDR) was flanked by PTPRT (20q13·11) and EYA2 (20q13·12). 210 (68·9%) patients had 'early MDS' without blast increase, 95 (31·1%) 'advanced' MDS with blast increase (5-19%). Additional chromosomal abnormalities (ACAs) were detected in 88/305 (28·9%) patients. Patients with advanced MDS more frequently had ACAs (P = 0·003) and had a higher mean number of ACAs (P = 0·020) and of molecular mutations (P = 0·060). Spliceosome mutations were frequent (U2AF1: n = 31/155; 20·0%; SRSF2: n = 31/159; 19·5%; SF3B1mut: n = 8/159; 5·0%). ASXL1mut (25/153; 16·3%) were associated with advanced MDS (P = 0·001). Presence of ≥3 ACAs (P = 0·003) and ASXL1mut (P = 0·002) were associated with worse 2-year survival. In conclusion, the cytogenetic subgroup of MDS with del(20q) has a good prognosis but may be further subclassified by additional cytogenetic and molecular lesions. U2AF1mut is overrepresented in MDS with del(20q), and ASXL1mut is prognostically adverse. © 2013 John Wiley & Sons Ltd.

  14. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

    Science.gov (United States)

    Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit

    2015-05-14

    Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

  15. Diagnostic and prognostic significance of cytogenetics in adult primary myelodysplastic syndromes.

    Science.gov (United States)

    Jotterand, M; Parlier, V

    1996-10-01

    Cytogenetic analysis has proven to be a mandatory part of the diagnosis of myelodysplastic syndromes (MDS) as well as a major indicator for predicting clinical course and outcome. This review concentrates on the cytogenetic classifications, the incidence and types of chromosome defects and the prognostic significance of the karyotype in adult primary MDS. Two cytogenetic classifications are currently used: one is based on the karyotype complexity (normal, single, double or complex defects), the other on clonal status (all metaphases normal, abnormal or admixture of normal and abnormal clones). Chromosome abnormalities are of both numerical and structural types. Aside from the 5q-syndrome, no specific clinico-cytogenetic entity has been reported. However, several distinct clinical and cellular features have been identified that correlate with the presence of specific chromosome defects such as inv(3)/t(3;3), +6, t(5;12), del(17p) and del(20q). The presence of complex defects is associated with reduced survival and a high risk of leukemic transformation. Among single defects, specific abnormalities may define distinct prognostic groups. Patients with del(5q) as a sole chromosome defect and a refractory anemia without excess of blasts have a favourable prognosis. For patients with trisomy 8 or monosomy 7 there may be distinct types of clinical evolution. Most patients with the 3q21q26 syndrome have a short survival. The presence of two chromosome defects may constitute an independent cytogenetic entity probably associated with relative poor prognosis. Karyotypic evolution generally represents a poor risk factor. The combination of cytogenetics with clinical and hematological features has proven to provide for a better prediction of patients' survival, leukemic transformation and response to treatment. Several scoring systems have been developed. They have to be improved by the study of new patients according to strict clinical and cytogenetic criteria and by the

  16. A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

    Science.gov (United States)

    Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen

    2017-07-01

    To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

  17. Report on outcomes of hypomethylating therapy for analyzing prognostic value of Revised International Prognostic Scoring System for patients with lower-risk myelodysplastic syndromes.

    Science.gov (United States)

    Lee, Yoo Jin; Park, Sung Woo; Lee, In Hee; Ahn, Jae Sook; Kim, Hyeoung Joon; Chung, Joo Seop; Shin, Ho Jin; Lee, Won Sik; Lee, Sang Min; Joo, Young Don; Kim, Hawk; Lee, Ho Sup; Kim, Yang Soo; Cho, Yoon Young; Moon, Joon Ho; Sohn, Sang Kyun

    2016-10-01

    The outcomes for patients with lower-risk myelodysplastic syndromes (LR-MDS) by the International Prognostic Scoring System (IPSS) vary widely. For more precise prognostication, this study evaluates the prognostic value of revised IPSS with the response to hypomethylating therapy (HMT). Using the Korean MDS Working Party database, treatment outcomes for 236 patients with HMT were retrospectively evaluated. The patients were then reclassified into very low/low (VL/L), intermediate (INT), and high (H) risk groups according to IPSS-R. According to the HMT response, the 3-year overall survival (OS) did not differ between the response group (37.9 ± 9.1 %) and the stable group (52.9 ± 6.6 %, p = 0. 782). When reclassifying according to IPSS-R, 42 patients (20.8 %) were reclassified into the H risk group. Most of them did not have benefit from continued HMT and progressed to secondary failure. The median OS was 59.0 months (range, 40.0-77.9 months) for the VL/L risk group, 31 months (range, 22.7-439.3 months) for the INT risk group, and 20.0 months (range, 15.9-24.1 months) for the H risk group (p risk group according to IPSS-R (HR = 3.054, p risk according to IPSS-R (HR = 4.912, p = 0.003), and transformation to AML (HR = 2.158, p = 0.002). If IPSS-R reclassifies LR-MDS patients as H risk, these patients should be considered for early allo-HCT, regardless of the current benefits from HMT.

  18. Myelodysplastic syndrome at a large tertiary care community hospital: analysis according to the international prognostic scoring system.

    Science.gov (United States)

    Jaiyesimi, I A; Friedline, J A; Mattson, J C; Gyorfi, T; Davis, B H; Balasubramaniam, M; Al-Khalili, A; Burdakin, J; Decker, D; Zakalik, D; Neumann, K; Wilner, F

    2000-05-01

    The outcome of patients diagnosed myelodysplastic syndromes (MDS) between 1990 and 1997 from William Beaumont Hospital (WBH) was analyzed according to the International Prognostic Scoring System (IPSS) risk categorization. A retrospective study of 195 MDS patients wa s performed. Seventy-nine patients with MDS, in whom a karyotype was obtained and with an adequate follow-up were included in the final analysis. Cases of proliferative CMML (WBC > 12x10(9)/l) were excluded from the study. The overall median survival was 3.1 years, and median survival stratified by IPSS was 3.4, 4.1 and 0.5 years for the INT-1, INT-2 and high risk group and not yet reached for the low risk group. The overall survival by IPSS subcategorization were 6.88, 5.29, 5.30 and 2.12 years for the low, INT-1, INT-2, and high risk groups respectively. Cytogenetics were significant in predicting the overall survival. The IPSS score stratified patients into risk categories for development of AML. The risk of development into AML was 8, 8, 33 and 54% for the low, INT-1, INT-2 and high risk groups, respectively. We conclude that IPSS score can be useful in predicting survival and AML evolution in some MDS patients.

  19. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  20. Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry.

    Science.gov (United States)

    Waszczuk-Gajda, Anna; Mądry, Krzysztof; Machowicz, Rafał; Drozd-Sokołowska, Joanna; Stella-Hołowiecka, Beata; Mital, Andrzej; Obara, Agata; Szmigielska-Kapłon, Anna; Sikorska, Anna; Subocz, Edyta; Jędrzejczak, Wiesław W; Dwilewicz-Trojaczek, Jadwiga

    2016-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients. Transfusion-dependent patients develop secondary iron overload. The influence of serum ferritin (SF) concentration on survival and acute myeloid leukemia transformation in MDS patients remains controversial. The data for the Central European population is scarce and so far there is no description for Poland. The aim of this study was to perform a retrospective analysis of the relationship of SF concentration with red blood cell transfusion dependency, survival and transformation to acute myeloid leukemia. We retrospectively evaluated the data of the 819 MDS patients (58% male; median age 70 years) included in the MDS Registry of the MDS Section of the Polish Adult Leukemia Group (PALG). Analyses were performed on 190 patients diagnosed with MDS, maximal 6 months before inclusion to the registry in order to avoid selection bias (a shorter survival of higher risk MDS patients). Patients with hyperferritinemia higher than 1000 ng/L vs. patients with SF concentration lower than 1000 ng/L had a median survival of 320 days vs. 568 days, respectively (p log-rank = 0.014). The following factors were found to significantly worsen survival: RBC-transfusion dependence (p = 0.0033; HR 2.67L), platelet transfusion dependence (p = 0.0071; HR 3.321), hemoglobin concentration lower than 10 g/dL (p = 0.0036; HR 2.97), SF concentration higher than 1000 ng/L (p = 0.0023; HR = 2.94), platelet count lower than 10 G/L (p = 0.0081 HR = 5.04), acute leukemia transformation (p = 0.0081; HR 1.968). Taking into account the relatively low number of patients in previous studies exploring hyperferritinemia in MDS, the results of the first Polish

  1. Myelodysplastic syndromes: a scoring system with prognostic significance.

    Science.gov (United States)

    Mufti, G J; Stevens, J R; Oscier, D G; Hamblin, T J; Machin, D

    1985-03-01

    141 patients with MDS were classified according to the FAB criteria and followed up for a period of 4-192 months. It was recognized that patients with RAEBT had a uniformly poor prognosis. However, there was a wide variation in survival among the other subgroups. A score of 1 was assigned to each of the following presenting haematological features: bone marrow blasts greater than or equal to 5%, platelets less than or equal to 100 X 10(9)/l, neutrophils less than or equal to 2.5 X 10(9)/l and Hb less than or equal to 10.0 g/dl. Therefore the score for each patient ranged between 0 and 4. There were no statistically significant differences between those patients who scored 0 or 1, or between those who scored 2 and 3. Therefore patients were put into three groups: Group A (score 0 or 1), Group B (score 2 or 3), Group C (score 4). The differences in survival between each of the three groups are highly significant (P less than 0.00001). This system further separates patients with RA, RAS, RAEB into good and bad prognostic groups. This study also confirms that deaths due to cytopenias are more common than those due to transformation to AML. The use of this scoring system in conjunction with the FAB criteria for MDS should serve as a prognostic tool on which to base treatment.

  2. Time-dependent changes in mortality and transformation risk in MDS.

    Science.gov (United States)

    Pfeilstöcker, Michael; Tuechler, Heinz; Sanz, Guillermo; Schanz, Julie; Garcia-Manero, Guillermo; Solé, Francesc; Bennett, John M; Bowen, David; Fenaux, Pierre; Dreyfus, Francois; Kantarjian, Hagop; Kuendgen, Andrea; Malcovati, Luca; Cazzola, Mario; Cermak, Jaroslav; Fonatsch, Christa; Le Beau, Michelle M; Slovak, Marilyn L; Levis, Alessandro; Luebbert, Michael; Maciejewski, Jaroslaw; Machherndl-Spandl, Sigrid; Magalhaes, Silvia M M; Miyazaki, Yasushi; Sekeres, Mikkael A; Sperr, Wolfgang R; Stauder, Reinhard; Tauro, Sudhir; Valent, Peter; Vallespi, Teresa; van de Loosdrecht, Arjan A; Germing, Ulrich; Haase, Detlef; Greenberg, Peter L

    2016-08-18

    In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making. © 2016 by The American Society of Hematology.

  3. Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome.

    Science.gov (United States)

    Shaffer, Brian C; Ahn, Kwang Woo; Hu, Zhen-Huan; Nishihori, Taiga; Malone, Adriana K; Valcárcel, David; Grunwald, Michael R; Bacher, Ulrike; Hamilton, Betty; Kharfan-Dabaja, Mohamed A; Saad, Ayman; Cutler, Corey; Warlick, Erica; Reshef, Ran; Wirk, Baldeep Mona; Sabloff, Mitchell; Fasan, Omotayo; Gerds, Aaron; Marks, David; Olsson, Richard; Wood, William Allen; Costa, Luciano J; Miller, Alan M; Cortes, Jorge; Daly, Andrew; Kindwall-Keller, Tamila L; Kamble, Rammurti; Rizzieri, David A; Cahn, Jean-Yves; Gale, Robert Peter; William, Basem; Litzow, Mark; Wiernik, Peter H; Liesveld, Jane; Savani, Bipin N; Vij, Ravi; Ustun, Celalettin; Copelan, Edward; Popat, Uday; Kalaycio, Matt; Maziarz, Richard; Alyea, Edwin; Sobecks, Ron; Pavletic, Steven; Tallman, Martin; Saber, Wael

    2016-06-01

    To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS). We examined 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT. Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 10(9)/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort. The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS. © 2016 by American Society of Clinical Oncology.

  4. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

  5. Pediatric MDS: GATA screen the germline.

    Science.gov (United States)

    Stieglitz, Elliot; Loh, Mignon L

    2016-03-17

    In this issue of Blood, Wlodarski and colleagues demonstrate that as many as 72% of adolescents diagnosed with myelodysplastic syndrome (MDS) and monosomy 7 harbor germline mutations in GATA2. Although pediatric MDS is a very rare diagnosis, occurring in 0.8 to 4 cases per million, Wlodarski et al screened >600 cases of primary or secondary MDS in children and adolescents who were enrolled in the European Working Group on MDS consortium over a period of 15 years. The overall frequency of germline GATA2 mutations in children with primary MDS was 7%, and 15% in those presenting with advanced disease. Notably, mutations in GATA2 were absent in patients with therapy-related MDS or acquired aplastic anemia.

  6. Myelodysplastic syndromes: histopathology as prognostic factor

    Directory of Open Access Journals (Sweden)

    Romeo Maura

    2001-01-01

    Full Text Available Bone marrow biopsy allows evaluation of cellularity, abnormal localization of immature precursors and fibrosis in myelodysplastic syndrome. It has been considered important to make diagnosis and prognosis of this disorder. The object of this study evaluated the influence of histopathological parameters, such as cellularity, erythroid/myeloid ratio, abnormal localization of immature precursors and marrow fibrosis, on survival of myelodysplastic syndrome patients. Forty-six patients, admitted from April 1985 to June 1998, and diagnosed as being myelodysplastic syndrome according to French-American-British criteria, were selected. There were 20 males and 26 females, with median age of 61 years. Forty-six bone marrow smears and 36 trephine biopsies were reviewed. Mean survival of hypocellular cases was 64.8 months and of hyper and normocellular cases was 31.8 months. Patients with predominance of erythroid hyperplasia had mean survival of 50.8 months, greater than those with predominance of myeloid hyperplasia (20.3 months. There was no statistical difference in survival of patients with or without abnormal localization of immature precursors and with or without marrow fibrosis. Bone marrow biopsy is a useful tool for the identification of parameters that influence prognosis in myelodysplastic syndrome. Hypocellularity and erythroid hyperplasia were correlated with longer survival while myeloid hyperplasia with poorer survival.

  7. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

    NARCIS (Netherlands)

    Lubbert, M.; Suciu, S.; Baila, L.; Ruter, B.H.; Platzbecker, U.; Giagounidis, A.; Selleslag, D.; Labar, B.; Germing, U.; Salih, H.R.; Beeldens, F.; Muus, P.; Pfluger, K.H.; Coens, C.; Hagemeijer, A.; Eckart Schaefer, H.; Ganser, A.; Aul, C.; Witte, T.J.M. de; Wijermans, P.W.

    2011-01-01

    PURPOSE: To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. PATIENTS AND METHODS: Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years)

  8. Brugada syndrome: the prognostic dilemma and value of sincope.

    Science.gov (United States)

    Paparella, G; Sarkozy, A; Brugada, P

    2009-08-01

    Since its first description in 1992 as a new clinical entity, the Brugada syndrome has stimulated great interest among physicians and basic scientists. In 2002 and 2005, two consensus conferences have respectively defined the diagnostic criteria for the syndrome. Currently the diagnosis of Brugada syndrome is based on a combination of clinical events (syncope and/or sudden cardiac death due to malignant ventricular arrhythmias) and electrocardiographic features (pathognomonic ST-segment elevation morphology). In the last years, many advances have been done in the knowledge about the genetic basis, the cellular mechanisms responsible for the typical electrocardiography features, susceptibility to ventricular arrhythmias and risk stratification. The implantable cardioverter defibrillator remains the only therapeutic option of proven efficacy for primary and secondary prophylaxis of sudden cardiac death. Identification of high risk subjects is one of the major goals in clinical decision-making. Syncope is ubiquitously recognized as a bad prognostic marker in Brugada syndrome. However, young individuals with this disease may suffer from vaso-vagal instead of arrhythmic syncope. The prognostic significance of syncope in patients with Brugada syndrome is discussed in this review.

  9. Myelodysplastic Syndromes (MDS)

    Science.gov (United States)

    ... however you can Daughter's dying wish became mother's motivation Be The Match Blog Stories Anna, transplant recipient ... Jobs Job application FAQs E-Verify Career events Employee benefits About us Bea, transplant recipient Be The ...

  10. Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival.

    Science.gov (United States)

    Santamaría, Carlos; Ramos, Fernando; Puig, Noemi; Barragán, Eva; de Paz, Raquel; Pedro, Carme; Insunza, Andrés; Tormo, Mar; Del Cañizo, Consuelo; Diez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Sánchez del Real, Javier; Hernández, Montserrat; Chillón, Carmen; Sanz, Guillermo F; García-Sanz, Ramón; San Miguel, Jesús F; González, Marcos

    2012-12-01

    Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were: WT1 detection (p = 0.014), low TET2 (p = 0.002), and low IER3 expression (p = 0.025). WT1 detection (p = 0.006) and low TET2 (p = 0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were: WT1 detection (p = 0.003), high EVI1 expression (p = 0.001), and undetectatable p15-CDKN2B (p = 0.037). WT1 expressers were associated with adverse clinical-biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable WT1 expression levels, and low TET2 and low IER3 expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only molecular marker displaying an independent prognostic value in both OS and TFS.

  11. MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells.

    Science.gov (United States)

    Dong, Wen; Wu, Lei; Sun, Houfang; Ren, Xiubao; Epling-Burnette, Pearlie K; Yang, Lili

    2016-11-01

    Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, pMDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, pMDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (pMDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression.

  12. Lessons from the atomic bomb about secondary MDS.

    Science.gov (United States)

    Hata, Tomoko; Imanishi, Daisuke; Miyazaki, Yasushi

    2014-12-01

    Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed.

  13. Mutational profiling in patients with MDS: ready for every-day use in the clinic?

    Science.gov (United States)

    Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten

    2015-03-01

    Multiple recurrent somatic mutations were identified in the majority of patients with myelodysplastic syndromes (MDS), but investigating the broad spectrum of molecular markers in MDS exceeds many laboratories' capacity when traditional molecular techniques are used. High-throughput second generation sequencing (=next-generation sequencing, NGS) has proven to be applicable for comprehensive biomarker mutation analyses allowing to increase diagnostic sensitivity and accuracy and to improve risk stratification and prognostication in addition to cytomorphology and cytogenetic analysis in patients with MDS. Amplicon deep-sequencing enables comprehensive biomarker analysis in a multitude of patients per investigation in an acceptable turn-around time and at affordable costs. Comprehensive myeloid marker panels were successfully introduced into diagnostic practice. Therefore, molecular mutation analysis is ready for use in all patients with suspected MDS, may contribute to risk stratification in possible candidates for allogeneic stem cell transplantation, and should become an integral part of clinical research studies in MDS patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Prognostic evaluation of Guillain-Barre' syndrome

    International Nuclear Information System (INIS)

    Shah, F.U.; Saeed, A.M.; Badsha, M.; Tariq, M.

    2001-01-01

    Objective: To study the mortality morbidity and the role of specific therapy in guillain-bare' syndrome (GBS). Design: This was a prospective study. Place and Duration of Study: This study was conducted in the department of Neurology, PIMS, Islamabad from January, 1999 to September, 2000. Subjects and Methods: Forty-eight patients with acute symmetrical flaccid motor weakness, which developed with-in a period of four weeks, were included. These patients were assessed at admission discharge and after 2 and 6 months according to the modified Rankin Scale Scope. Patients with sensory level and those having marked and persistent asymmetry of neurological signs were excluded from the study. Results: The modified disability score (DS) n the patients at admission was 2.-5 in 2,11,19 and 16 patients respectively. Respiratory failure was present in 16 patient. Six patients expired. After 2 months, 19 recovered, 10 were lost and diability was present in 13 patients. After 6 months, 20 recovered and 5 were disabled. Specific treatment was given to 23 patients, plasmaphaeresis was done in 10 patients, gammaglobulin given to 4 patients and both in 9 patients. In plasmaphaeresis group at admission DS was 4, 5 and 7 in 3 patients respectively. Three patients expired. At 2 months, 2 recovered, 3 disable while 2 patient were lost, at 6 months 2 recovered, 1 disable while 4 were lost. Similarly, in gammaglobulin group DS was 4 and 5 in 3 and 1 patient at admission. At 2 months, 3 recovered and 1 was disable. In the combined group, admission DS was 4 in 1 and 5 in the 8 patients. At 2 months, 3 recovered, 5 disabled and 1 patient was lost. At 6 months, 3 recovered and 1 patient was lost. At 6 months, 3 recovered and 2 patients were disabled. In the non-specific treatment group, DS was 2 and 3 in 2 and 11 patients at admission. At 2 months, 9 recovered and 3 were disabled while 1 was lost. At 6 months, 11 patients recovered and 2 were disabled. In the control group, at admission, DS

  15. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; van Marwijk Kooy, Marinus; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Croon-de Boer, Fransien; Eefting, Matthijs; Jie, Kon-Siong G.; van de Loosdrecht, Arjan A.; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  16. [Progress of cytogenetic detection in myelodysplastic syndromes].

    Science.gov (United States)

    Zhou, Qing-Bing; Hu, Xiao-Mei; Liu, -Feng; Ma, Rou

    2011-12-01

    In recent years, significant progresses have been got in study on pathogenesis, treatment and prognosis of myelodysplastic syndromes (MDS), especially on use of new technology, that has great importance for cytogenetics of MDS. Recently, the progress of cytogenetic detection in MDS is very remarkable. Based on the metaphase cytogenetics (MC) method, prognostic significance of cytogenetics in MDS was clarified gradually. For example, people have known the prognostic significance of 12 p-, 11 q-, +21, t(11(q23)), although these genetic abnormalities are rare in the MDS. In addition, chromosome mutation emerged in the process of MDS may indicate the poor prognosis. On the other hand, with the use of SNP-A and aCGH in the study of genetics, MDS cytogenetic abnormality detection rate has been further improved and can reach to 78%. At the same time, some of MDS patients with the "normal karyotype" detected by MC have new hidden aberrations through the SNP or CGH detection, and these patients have a poorer prognosis. In this review, the advances of study on cytogenetic detection for MDS based on MC and SNP-A or aCGH methods are summarized.

  17. MDS MIC Catalog Inputs

    Science.gov (United States)

    Johnson-Throop, Kathy A.; Vowell, C. W.; Smith, Byron; Darcy, Jeannette

    2006-01-01

    This viewgraph presentation reviews the inputs to the MDS Medical Information Communique (MIC) catalog. The purpose of the group is to provide input for updating the MDS MIC Catalog and to request that MMOP assign Action Item to other working groups and FSs to support the MITWG Process for developing MIC-DDs.

  18. The prognostic value of pyeloectasis in infants with urinary syndrome

    Directory of Open Access Journals (Sweden)

    Kozachkovsky A.E.

    2014-03-01

    Full Text Available Aim of the study was of to determine prognostic value of pyeloectasias in the structure of urinary system diseases including the frequency of pyeloectasia and its clinical significance in young children at the stage of hospital treatment at the infectious disease department. The diagnosis of the diseases and malformations of the kidneys and the urinary tract ultrasound study of 192 children at the age of 1 month to – 2,5 years was conducted. Ultrasound study of the urinary system was performed by a standardized technique using ultrasound scanner «SIEMENS SONOLINE G40» (company Siemens, Germany using a 2.5-5 MHz convex probe, and 7.5-10 MHz linear transducer. Pyeloectasias are the most often sonologic symptom in young age children presenting urinary syndrome (75% of researches. Obtained results of catamnestic follow ups showed that sizes of renal pelvis of more than 10 mm are the risk factors for acute pyelonephritis development.

  19. Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome.

    Science.gov (United States)

    Lee, J-H; Lee, J-H; Shin, Y-R; Lee, J-S; Kim, W-K; Chi, H-S; Park, C-J; Seo, E-J; Lee, K-H

    2003-02-01

    We retrospectively studied 227 patients with MDS (1) to identify the prognostic factors of survival and acute leukemia evolution in Korean patients with MDS, (2) to apply different prognostic scoring systems to the same group of patients, and (3) to compare the FAB with the WHO classification. Six scoring systems were applied to the patients, and the FAB and WHO classifications were compared. The patients' median age was 57 years. The median survival time was 21 months, and age, dysgranulopoiesis and the IPSS cytogenetic groups were independent prognostic factors for survival. Acute leukemia occurred in 34 patients, and the cumulative incidence was 27.1% at 3 years. Marrow blast percentage was the only independent prognostic factor for acute leukemia evolution. Most scoring systems successfully discriminated risk groups for survival and acute leukemia evolution, but patient distribution into risk groups varied according to the scoring systems. Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively. In summary, our MDS patients had different disease natures from those of Western countries regarding clinical features, prognostic factors and cytogenetic profiles. Although the WHO classification seems to improve the FAB classification, further studies are warranted to validate the utility of the WHO classification before it is accepted for routine clinical use. Our study has the limitations of retrospective analysis, and our results should be verified in future prospective studies.

  20. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis.

    Science.gov (United States)

    Leitch, Heather A; Parmar, Ambica; Wells, Richard A; Chodirker, Lisa; Zhu, Nancy; Nevill, Thomas J; Yee, Karen W L; Leber, Brian; Keating, Mary-Margaret; Sabloff, Mitchell; St Hilaire, Eve; Kumar, Rajat; Delage, Robert; Geddes, Michelle; Storring, John M; Kew, Andrea; Shamy, April; Elemary, Mohamed; Lenis, Martha; Mamedov, Alexandre; Ivo, Jessica; Francis, Janika; Zhang, Liying; Buckstein, Rena

    2017-10-01

    Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease-modifying agents. This provides additional evidence that ICT may confer clinical benefit. © 2017 John Wiley & Sons Ltd.

  1. [Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia].

    Science.gov (United States)

    Ma, Yan; Chen, Bo-Bin; Wang, Xiao-Qin; Xu, Xiao-Ping; Lin, Guo-Wei

    2015-12-01

    To establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort. All patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models. A total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model

  2. Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance

    NARCIS (Netherlands)

    Swart, L. de; Smith, A.; MacKenzie, M.; Symeonidis, A.; Neukirchen, J.; Mikulenkova, D.; Vallespi, T.; Zini, G.; Paszkowska-Kowalewska, M.; Kruger, A.; Saft, L.; Fenaux, P.; Bowen, D.; Hellstrom-Lindberg, E.; Cermak, J.; Stauder, R.; Tatic, A.; Holm, M.S.; Malcovati, L.; Madry, K.; Droste, J.A.; Blijlevens, N.M.; Witte, T.J. de; Germing, U.

    2017-01-01

    The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard

  3. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN.

    Science.gov (United States)

    Jabbour, Elias; Short, Nicholas J; Montalban-Bravo, Guillermo; Huang, Xuelin; Bueso-Ramos, Carlos; Qiao, Wei; Yang, Hui; Zhao, Chong; Kadia, Tapan; Borthakur, Gautam; Pemmaraju, Naveen; Sasaki, Koji; Estrov, Zeev; Cortes, Jorge; Ravandi, Farhad; Alvarado, Yesid; Komrokji, Rami; Sekeres, Mikkael A; Steensma, David P; DeZern, Amy; Roboz, Gail; Kantarjian, Hagop; Garcia-Manero, Guillermo

    2017-09-28

    Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m 2 intravenously/subcutaneously daily or decitabine 20 mg/m 2 intravenously daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between November 2012 and February 2016, 113 patients were treated: 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate 1-risk patients. The median number of cycles received was 9. The ORRs were 70% and 49% ( P = .03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine ( P = .2). Cytogenetic response rates were 61% and 25% ( P = .02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months: 20 and 13 months for patients treated with decitabine and azacitidine, respectively ( P = .1). Treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225). © 2017 by The American Society of Hematology.

  4. IER3 Expression in Childhood Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    de Vries, Andrica; Zwaan, Christian M.; Danen van Ooschot, Astrid

    Background: Childhood myelodysplastic syndrome (MDS) is a rare disease accounting for less than 5% of all hematological malignancies. In about 50% of the MDS cases an abnormal karyotype is found by conventional karyotyping, of which chromosome 6 is involved in 10%. The immediate-early-response 3...... (IER3) gene, which is located on chromosome 6p21, encodes for a glycoprotein that plays a role in the regulation of apoptosis and cell cycle progression. Recently, it was shown that IER3 gene aberrations frequently occur in adult MDS patients, which are not restricted to patients with chromosome 6...... aberrations and that low IER3 expression was associated with a worse outcome. Therefore, we investigated the frequency and prognostic impact of IER3 expression in childhood MDS. Methods: IER3 mRNA expression was determined by quantitative real-time PCR in 58 childhood MDS patients of which 17 carried...

  5. Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation.

    Science.gov (United States)

    Zhao, Sida; Zhao, Youshan; Guo, Juan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang

    2017-03-06

    The role of mesenchymal stromal cells (MSCs) in the pathogenesis of myelodysplastic syndromes (MDS) has been increasingly addressed, but has yet to be clearly elucidated. In this investigation, we found that MDS cells proliferated to a greater extent on MDS-derived MSCs compared to normal MSCs. Matrix metalloproteinase 1(MMP1), which was downregulated in MDS-MSCs, was identified as an inhibitory factor of MDS cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased MDS cell proliferation. Further investigations indicated that MMP1 induced apoptosis of MDS cells by interacting with PAR1 and further activating the p38 MAPK pathway. Inhibition of either PAR1 or p38 MAPK can reverse the apoptosis-inducing effect of MMP1. Taken together, these data indicate that downregulation of MMP1 in MSCs of MDS patients may contribute to the reduced capacity of MSCs to restrict MDS cell proliferation, which may account for the malignant proliferation of MDS cells.

  6. Azacitidine improves outcome in higher-risk MDS patients with chromosome 7 abnormalities: a retrospective comparison of GESMD and GFM registries.

    Science.gov (United States)

    Díez-Campelo, María; Lorenzo, Jose I; Itzykson, Raphael; Rojas, Silvia M; Berthon, Céline; Luño, Elisa; Beyne-Rauzy, Odile; Perez-Oteyza, Jaime; Vey, Norbert; Bargay, Joan; Park, Sophie; Cedena, Teresa; Bordessoule, Dominique; Muñoz, Juan A; Gyan, Emmanuel; Such, Esperanza; Visanica, Sorin; López-Cadenas, Félix; de Botton, Stéphane; Hernández-Rivas, Jesús M; Ame, Shanti; Stamatoullas, Aspasia; Delaunay, Jacques; Salanoubat, Celia; Isnard, Françoise; Guieze, Romain; Pérez Guallar, Joan; Badiella, Llorenc; Sanz, Guillermo; Cañizo, Consuelo; Fenaux, Pierre

    2018-05-01

    Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK. © 2018 John Wiley & Sons Ltd.

  7. Myelodysplastic Syndrome and Histone Deacetylase Inhibitors: “To Be or Not to Be Acetylated”?

    Science.gov (United States)

    Stintzing, Sebastian; Kemmerling, Ralf; Kiesslich, Tobias; Alinger, Beate; Ocker, Matthias; Neureiter, Daniel

    2011-01-01

    Myelodysplastic syndrome (MDS) represents a heterogeneous group of diseases with clonal proliferation, bone marrow failure and increasing risk of transformation into an acute myeloid leukaemia. Structured guidelines are developed for selective therapy based on prognostic subgroups, age, and performance status. Although many driving forces of disease phenotype and biology are described, the complete and possibly interacting pathogenetic pathways still remain unclear. Epigenetic investigations of cancer and haematologic diseases like MDS give new insights into the pathogenesis of this complex disease. Modifications of DNA or histones via methylation or acetylation lead to gene silencing and altered physiology relevant for MDS. First clinical trials give evidence that patients with MDS could benefit from epigenetic treatment with, for example, DNA methyl transferase inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi). Nevertheless, many issues of HDACi remain incompletely understood and pose clinical and translational challenges. In this paper, major aspects of MDS, MDS-associated epigenetics and the potential use of HDACi are discussed. PMID:21629744

  8. Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

    Science.gov (United States)

    Attar, Eyal C; Amrein, Philip C; Fraser, James W; Fathi, Amir T; McAfee, Steven; Wadleigh, Martha; Deangelo, Daniel J; Steensma, David P; Stone, Richard M; Foster, Julia; Neuberg, Donna; Ballen, Karen K

    2013-09-01

    We conducted a phase I dose escalation study to determine the maximal tolerated dose of bortezomib that could be combined with standard dose lenalidomide in patients with MDS or AML. Treatment consisted of bortezomib (IV) on Days 1, 4, 8, and 11 and lenalidomide 10mg daily (PO) days 1-21 in 28 day cycles for up to 9 cycles. 23 patients (14 MDS/CMML, 9 AML) were enrolled. The maximally tested dose of bortezomib, 1.3mg/m(2), was tolerable in this regimen. Responses were seen in patients with MDS and AML. Further testing of this regimen is planned. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Monitoring treatment efficiency in MDS at the molecular level; possibilities now and in the future.

    NARCIS (Netherlands)

    Dijk, J.P. van; Witte, T.J.M. de

    2004-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow (BM) diseases. MDS patients suffer from bone marrow failure because of the expansion of a malignant clone, resulting in abnormal differentiation of blood cells and severe pancytopenias. MDS patients have a high propensity for

  10. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS

    Science.gov (United States)

    Scott, Bart L.; Fang, Min; Shulman, Howard M.; Gyurkocza, Boglarka; Myerson, David; Pagel, John M.; Platzbecker, Uwe; Ramakrishnan, Aravind; Radich, Jerald P.; Sandmaier, Brenda M.; Sorror, Mohamed; Stirewalt, Derek L.; Wilson, Wendy A.; Storb, Rainer; Appelbaum, Frederick R.; Gooley, Ted

    2012-01-01

    Clonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics. PMID:22767498

  11. Therapy-related myelodysplastic syndrome: morphologic subclassification may not be clinically relevant.

    Science.gov (United States)

    Singh, Zeba N; Huo, Dezheng; Anastasi, John; Smith, Sonali M; Karrison, Theodore; Le Beau, Michelle M; Larson, Richard A; Vardiman, James W

    2007-02-01

    In practice, cases of therapy-related myelodysplastic syndrome (t-MDS) are often classified according to morphologic schemes used for de novo MDS. However, there are few data addressing the appropriateness of such classification. We studied 155 patients with therapy-related acute myeloid leukemia (t-AML)/t-MDS to determine whether subclassification by the World Health Organization (WHO) criteria for de novo MDS provides prognostic information in t-MDS. In addition, we assessed whether cytogenetic stratification by the International Prognostic Scoring System (IPSS) guidelines or karyotypic complexity was prognostically important. We found no differences in median survival times among patients classified into the different WHO subgroup of MDS or according to their bone marrow blast percentage; our results indicate a uniformly poor outcome in t-MDS regardless of morphologic classification. However, significant survival differences correlated with cytogenetic stratification according to IPSS guidelines and/or karyotypic complexity. We found only a borderline difference in median survival of patients with an initial t-MDS diagnosis compared with patients with an initial t-AML diagnosis.

  12. Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics has received considerable attention recently as an emerging sub-discipline within SHM. Prognosis is here strictly defined as “predicting the time at...

  13. Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype.

    Science.gov (United States)

    Sallman, David A; Cluzeau, Thomas; Basiorka, Ashley A; List, Alan

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by bone marrow cytological dysplasia and ineffective hematopoiesis in the setting of recurrent somatic gene mutations and chromosomal abnormalities. The underlying pathogenic mechanisms that drive a common clinical phenotype from a diverse array of genetic abnormalities have only recently begun to emerge. Accumulating evidence has highlighted the integral role of the innate immune system in upregulating inflammatory cytokines via NF-κB activation in the pathogenesis of MDS. Recent investigations implicate activation of the NLRP3 inflammasome in hematopoietic stem/progenitor cells as a critical convergence signal in MDS with consequent clonal expansion and pyroptotic cell death though caspase-1 maturation. Specifically, the alarmin S100A9 and/or founder gene mutations trigger pyroptosis through the generation of reactive oxygen species leading to assembly and activation of the redox-sensitive NLRP3 inflammasome and β-catenin, assuring propagation of the MDS clone. More importantly, targeted inhibition of varied steps in this pathway restore effective hematopoiesis. Together, delineation of the role of pyroptosis in the clinical phenotype of MDS patients has identified novel therapeutic strategies that offer significant promise in the treatment of MDS.

  14. [Myelodysplastic syndromes: pathophysiology, clinical and biological features].

    Science.gov (United States)

    Becha, Mohamed; Braham Jmili, Néjia

    2015-01-01

    Myelodysplastic syndromes (MDS) are hemopathies very common in geriatric practice. They are characterized by qualitative morphological abnormalities of one or more myeloid lineages responsible for an ineffective hematopoiesis, and therefore cytopenias of central origin contrasting with a usually rich bone marrow wealth. The MDS are asymptomatic in half of the cases and their discovery is a result of systematic blood analysis or tests to explore another disease. The evolution is marked by worsening cytopenias, and the risk of acute myeloid leukemia transformation with poor prognosis because frequently chemoresistant. The diagnosis of MDS is pronounced after a clinico-biological confrontation to discuss the differential diagnosis taking into account all clinical and cytological data, results of conventional cytogenetics and evolution after vitamin therapy. Knowledge more depth on MDS refine MDS classification criteria by developing successive classifications (FAB 1982, WHO 2001 and 2008) which aim the identification of MDS groups with clinical, biological and common prognostic. The treatment of MDS is essentially symptomatic. The development of new targeted therapeutic strategies enables high hopes in a context where treatment options are a difficult choice, because the advanced age of most patients. Finally, detailed knowledge of risk factors and prognostic scores are very useful to make the best treatment decisions.

  15. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    Myelodysplastic changes mimicking MDS following treatment for osteosarcoma Ditte Juel Adolfsen Løhmann, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark Authors: Ditte Juel Adolfsen Løhmann and Henrik Hasle. Therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-MDS....../AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up to two...... MDS (refractory anaemia with excess blasts) with monosomy 7 was found and a hematopoietic stem cell transplant was performed. In the other case MDS without excess of blasts was found and a spontaneous normalization of the biochemistry occurred. In conclusion in our study most patients treated...

  16. Enumerating bone marrow blasts from nonerythroid cellularity improves outcome prediction in myelodysplastic syndromes and permits a better definition of the intermediate risk category of the Revised International Prognostic Scoring System (IPSS-R).

    Science.gov (United States)

    Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Blanco, María Laura; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Meritxell; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2017-07-01

    The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. Twenty-four percent of patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS risk of dying with AML. Regarding MDS-E, 51% patients classified into the intermediate category were reclassified into higher-risk ones and showed shorter OS and time to AML. In this subgroup of MDS, IPSS-R was capable of splitting our series in five groups with significant differences in OS only when blasts were assessed from NECs. In conclusion, our easy-applicable approach improves prognostic assessment of MDS patients. © 2017 Wiley Periodicals, Inc.

  17. Serum albumin is an important prognostic factor for carotid blowout syndrome

    International Nuclear Information System (INIS)

    Lu Hsuehju; Chen Kuowei; Chen Minghuang; Tzeng Chenghwai; Chang Peter Muhsin; Yang Muhhwa; Chu Penyuan; Tai Shyhkuan

    2013-01-01

    Carotid blowout syndrome is a severe complication of head and neck cancer. High mortality and major neurologic morbidity are associated with carotid blowout syndrome with massive bleeding. Prediction of outcomes for carotid blowout syndrome patients is important for clinicians, especially for patients with the risk of massive bleeding. Between 1 January 2001 and 31 December 2011, 103 patients with carotid blowout syndrome were enrolled in this study. The patients were divided into groups with and without massive bleeding. Prognostic factors were analysed with proportional hazard (Cox) regressions for carotid blowout syndrome-related prognoses. Survival analyses were based on the time from diagnosis of carotid blowout syndrome to massive bleeding and death. Patients with massive bleeding were more likely to have hypoalbuminemia (albumin 1000 cells/μl, P=0.041) and hypoalbuminemia (P=0.010) were important to prognosis. Concurrent chemoradiotherapy (P=0.007), elevated lactate dehydrogenase (>250 U/l; P=0.050), local recurrence (P=0.022) and hypoalbuminemia (P=0.038) were related to poor prognosis in carotid blowout syndrome-related death. In multivariate analysis, best supportive care and hypoalbuminemia were independent factors for both carotid blowout syndrome-related massive bleeding (P=0.000) and carotid blowout syndrome-related death (P=0.013), respectively. Best supportive care and serum albumin are important prognostic factors in carotid blowout syndrome. It helps clinicians to evaluate and provide better supportive care for these patients. (author)

  18. Translocation (6;15(q12;q15: A Novel Mutation in a Patient with Therapy-Related Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Saba F. Ali

    2015-01-01

    Full Text Available Most myelodysplastic syndromes (MDS present with loss or gain of chromosomal material and less commonly show translocations as a sole abnormality. In addition, certain translocations are more commonly seen in MDS than others, but to our knowledge, the presence of t(6;15 has not been reported in MDS, specifically therapy-related MDS (t-MDS cases. Patients with t-MDS, a group of heterogeneous stem cell related disorders resulting as a latent complication of cytotoxic and/or radiation therapy, generally tend to have a poorer prognosis than de novo MDS. We present a unique case of a patient who initially presented with acute myeloid leukemia (AML with a normal karyotype and FLT3-ITD and NPM1 mutations. The patient was successfully treated with chemotherapy and an autologous bone marrow transplant but subsequently developed a new FLT3-ITD negative t-MDS with a unique translocation, t(6;15(q12;q15, three years after transplant. To our knowledge, this unique sole translocation has never been reported in MDS or t-MDS and given her successful response to treatment and remission, presence of this translocation may have some prognostic value.

  19. Implication of microRNAs in the Pathogenesis of MDS

    Science.gov (United States)

    Fang, Jing; Varney, Melinda; Starczynowski, Daniel T.

    2016-01-01

    MicroRNAs (miRNAs) are significant regulators of human hematopoietic stem cells (HSC), and their deregulation contributes to hematological malignancies. Myelodysplastic syndromes (MDS) represent a spectrum of hematological disorders characterized by dysfunctional HSC, ineffective blood cell production, progressive marrow failure, and an increased risk of developing acute myeloid leukemia (AML). Although miRNAs have been primarily studied in AML, only recently have similar studies been performed on MDS. In this review, we describe the normal function and expression of miRNAs in human HSC, and describe mounting evidence that deregulation of miRNAs contributes to the pathogenesis of MDS. PMID:22571695

  20. Serologic features of primary Sjögren’s syndrome: clinical and prognostic correlation

    Science.gov (United States)

    García-Carrasco, Mario; Mendoza-Pinto, Claudia; Jiménez-Hernández, César; Jiménez-Hernández, Mario; Nava-Zavala, Arnulfo; Riebeling, Carlos

    2013-01-01

    Sjögren’s syndrome (SS) is a chronic inflammatory systemic autoimmune disease. The disease spectrum extends from sicca syndrome to systemic involvement and extraglandular manifestations, and SS may be associated with malignancies, especially non-Hodgkin’s lymphoma. Patients with SS present a broad spectrum of serologic features. Certain serological findings are highly correlated with specific clinical features, and can be used as prognostic markers. PMID:23525186

  1. Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro.

    Science.gov (United States)

    Calkoen, F G J; Vervat, C; van Pel, M; de Haas, V; Vijfhuizen, L S; Eising, E; Kroes, W G M; 't Hoen, P A C; van den Heuvel-Eibrink, M M; Egeler, R M; van Tol, M J D; Ball, L M

    2015-03-01

    Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets. Copyright © 2015. Published by Elsevier B.V.

  2. Clinical utility of lenalidomide in the treatment of myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Abou Zahr A

    2014-12-01

    Full Text Available Abdallah Abou Zahr,1 Ehab Saad Aldin,2 Rami S Komrokji,3 Amer M Zeidan4 1Section of Hematology/Oncology, Department of Internal Medicine, Mount Sinai Beth Israel, New York City, New York, NY, 2Department of Internal Medicine, Medstar Good Samaritan Hospital, Baltimore, MD, 3Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 4Division of Hematology, Department of Medicine, Yale University, New Haven, CT, USA Abstract: Myelodysplastic syndromes (MDS represent a heterogeneous group of acquired clonal hematopoietic disorders characterized by peripheral blood cytopenias, paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of leukemic transformation. Risk stratification, using different prognostic scores and markers, is at the core of MDS management. Deletion 5q [del(5q] MDS is a distinct class of MDS characterized by the haploinsufficiency of specific genes, microRNAs, and proteins, which has been linked to increased sensitivity to the drug lenalidomide. Phase II and III clinical trials have demonstrated the efficacy of lenalidomide in improving clinical outcomes of patients with del(5q MDS, including reduction in red blood cell transfusion requirements and improvements in quality of life. Lenalidomide has also demonstrated some activity in non-del(5q lower-risk MDS as well as higher-risk MDS, especially in combination with other agents. In this paper, we review the pathogenesis of del(5q MDS, the proposed mechanisms of action of lenalidomide, the major clinical trials that documented the activity of lenalidomide in different MDS populations, potential predictors of benefit from the drug and suggested mechanisms of resistance, and the use of combination strategies to expand the clinical utility of lenalidomide in MDS. Keywords: deletion 5q, lenalidomide, myelodysplastic syndromes, 5q-syndrome

  3. To chelate or not to chelate in MDS: That is the question!

    Science.gov (United States)

    Zeidan, Amer M; Griffiths, Elizabeth A

    2018-03-08

    Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used. The availability of effective oral ICT agents has reignited the controversy regarding ICT use in patients with MDS and IO. Here we summarize the studies evaluating the value of ICT in MDS and suggest a practical approach for use of these therapies. We also highlight controversies regarding use of ICT in MDS and discuss some ongoing efforts to answer these questions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. [Clinical Significance of ID4 Gene Mehtylation in Demethylation-Treated MDS Cell Line and 2 MDS Patients].

    Science.gov (United States)

    Kang, Hui-Yuan; Wang, Xin-Rong; Gao, Li; Wang, Wei; Li, Mian-Yang; Wang, Li-Li; Wang, Cheng-Bin; Yu, Li

    2015-04-01

    To evaluate significance of ID4 gene mehtylation in demethylating myelodysplastic syndrome(MDS) cell Line MUTZ1 and 2 patients with MDS. The methylation-specific PCR (MS-PCR) and reverse transcription-PCR (RT-PCR) were applied to identify the methylation status and gene expression of ID4 gene in MDS cell line MUTZ1, a patient with aplastic anemia(AA) and a donor with normal bone marrow (NBM). RT-PCR was applied to detect the ID4 gene expression status in MUTZ1 cell line treated with decitabine at 3 different concentrations. Then bisulfite sequencing PCR (BSP) was applied to detect ID4 gene methylation status in 2 MDS parients treated with decitabine. The MDS cell line MUTZ-1 displayed a complete methylation of ID4 gene promoter with little mRNA expression. Inversely, bone marrow of an AA patient and NBM showed complete unmethylation of this gene with intensity mRNA expression. With the increase of decitabine concentration, ID4 gene mRNA expression was more and more increased. After decitabine treatment, ID4 gene methylation-positive frequencies of both the 2 MDS patients were much more decreased than that of the first treatment. So, ID4 gene mRNA expression inhibited by promoter hypemethylation could be recovered by using demethylation medicine. ID4 as a new potential anti-oncogene suggests that its methylation may become a marker for selection and assessment of therapeutic schedules in patients with MDS.

  5. MDS. A disease with high radiation-risk

    International Nuclear Information System (INIS)

    Ban, Sadayuki; Sudo, Hitomi; Saegusa, Kumiko; Sagara, Masashi; Imai, Takashi

    2003-01-01

    A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the micronucleus (MN) frequency in peripheral T lymphocytes of twenty-three atomic bomb survivors with MDS and five normal individuals. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation-therapy, their unusual radiosensitivities may be related to their chromosomal or genomic instability. To explain the cause of unusual radiosensitivity, we measured the expression levels of four nucleotide excision repair (NER) genes (ERCC1, ERCC3, ERCC5 and XPC) in peripheral blood mononuclear cells using a reverse transcripts-polymerase chain reaction (RT-PCR) method. The ERCC5 gene was expressed at reduced levels in only one of 10 patients with mild symptom. Reduction of NER genes was expressed in four of 11 patients with severe symptom. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrnst was observed in some of MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that DNA repair defects and loss of G2/M arrest may be involved in the pathophysiology of disease progression. (authors)

  6. Evaluation of ten prognostic factors affecting the outcome of West syndrome.

    Science.gov (United States)

    Yilmaz, Sanem; Tekgul, Hasan; Serdaroglu, Gul; Akcay, Ayfer; Gokben, Sarenur

    2016-12-01

    The aim of this study is to assess the seizure and developmental outcome and to determine the prognostic factors affecting the outcome of West syndrome in an etiologically well-defined large cohort. Demographic features, treatment modalities, etiology, seizure and developmental outcome of 216 cases with West syndrome were recorded retrospectively. Ten prognostic factors possibly affecting the outcome of West syndrome including (1) gender, (2) age at the onset (3) presence of seizures prior to spasms, (4) presence of asymmetric spasm, (5) presence of abnormal neurological signs, (6) treatment lag, (7) etiology, (8) drug chosen as the initial treatment, (9) response to initial treatment regardless of the kind, (10) development of other seizure types after spasms were evaluated in terms of seizure and developmental outcome. Twelve percent of the cases were developmentally normal at the end of 2-year follow-up. Ongoing seizures requiring antiepileptic drug medication at the last follow-up were noted in 90 % of the cases. Hypoxia (29 %), metabolic disorders (11 %), infectious diseases (9 %) and cerebral developmental disorders (8 %) were the most frequent etiological factors. Five of the ten prognostic factors (presence of seizures prior to spasms, presence of abnormal neurological signs, response to initial treatment regardless of the kind, etiology and development of other seizure types after spasms) were found to be statistically significant prognostic factors predicting the outcome. In conclusion, West syndrome is still a catastrophic epileptic encephalopathy. Preventable causes still constitute a substantial portion of the etiological causes of West syndrome. Therefore, the prevention of avoidable causes is at least as important as the treatment.

  7. Strongly-MDS convolutional codes

    NARCIS (Netherlands)

    Gluesing-Luerssen, H; Rosenthal, J; Smarandache, R

    Maximum-distance separable (MDS) convolutional codes have the property that their free distance is maximal among all codes of the same rate and the same degree. In this paper, a class of MDS convolutional codes is introduced whose column distances reach the generalized Singleton bound at the

  8. Síndrome mielodisplásica secundária à quimio ou radioterapia: SMD relacionada a tratamento Myelodysplastic syndrome secondary to chemo: and radiotherapy MDS related to the treatment

    Directory of Open Access Journals (Sweden)

    Ronald F. Pinheiro

    2006-09-01

    Full Text Available O efeito leucemogênico dos agentes quimioterápicos após o tratamento para neoplasias é bem conhecido. Síndrome mielodisplásica secundária a quimio ou radioterapia, também denominada relacionada à terapia (SMD-t, geralmente ocorre quatro a sete anos após a exposição inicial ao agente quimio ou radioterápico, acomete habitualmente pacientes jovens, apresenta alta incidência de transformação para leucemia mielóide aguda (LMA, está associada a citopenias severas, displasia das três linhagens, celularidade medular reduzida e fibrose, e anormalidades citogenéticas em até 80% dos casos. As anormalidades mais freqüentes envolvem os cromossomos 5 e 7. No tocante à quimioterapia, os agentes alquilantes são as drogas mais comumente associadas com SMD-t. Quimioterápicos em altas doses usados como parte de regimes de condicionamento para transplantes de medula óssea e radioterapia, além dos esquemas COPP/ABV e BEACOPP, estão associados com SMD-t. Recentemente, drogas como azatioprina, cladribina e rituximab também foram relacionadas à SMD-t. Devido ao aumento da sobrevida de pacientes acometidos por neoplasias malignas, a SMD-t surge como efeito mutagênico desses tratamentos e confere prognóstico desfavorável.The leukaemogenic effect of chemotherapeutic agents after treatment for other malignancies have been well described. Myelodysplastic syndrome secondary to chemo- and radiotherapy (MDS-t usually develops four to seven years after the initial exposure to chemotherapy frequently involving young patients, shows a high incidence of transformation to AML, is associated with severe cytopenias, trilineage dysplasia, reduced marrow cellularity and fibrosis, and presents an incidence of chromosomal abnormalities of up to 80% of the cases. The most common abnormalities are related to chromosomes 5 and 7. Alkylating agents have been considered the most common drugs associated with MDS-t. High dose chemotherapy used as part of the

  9. A new prognostic index of severity of intellectual disabilities in Cornelia de Lange syndrome.

    Science.gov (United States)

    Cereda, Anna; Mariani, Milena; Rebora, Paola; Sajeva, Anna; Ajmone, Paola Francesca; Gervasini, Cristina; Russo, Silvia; Kullmann, Gaia; Valsecchi, Grazia; Selicorni, Angelo

    2016-06-01

    Cornelia de Lange syndrome is a well-known multiple congenital anomalies/intellectual disability syndrome with genetic heterogeneity and wide clinical variability, regarding the severity of both the intellectual disabilities and the physical features, not completely explained by the genotype-phenotype correlations known to date. The aim of the study was the identification of prognostic features, ascertainable precociously in the patient's life, of a better intellectual outcome and the development of a new prognostic index of severity of intellectual disability in CdLS patients. In 66 italian CdLS patients aged 8 years or more, we evaluated the association of the degree of intellectual disability with various clinical parameters ascertainable before 6 months of life and with the molecular data by the application of cumulative regression logistic model. Based on these results and on the previously known genotype-phenotype correlations, we selected seven parameters to be used in a multivariate cumulative regression logistic model to develop a prognostic index of severity of intellectual disability. The probability of a mild ID increases with the reducing final score less than two, the probability of a severe ID increases with the increasing final score more than three. This prognostic index allows to define, precociously in the life of a baby, the probability of a better or worse intellectual outcome in CdLS patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Prognostic factors of synkinesis after Bell's palsy and Ramsay Hunt syndrome.

    Science.gov (United States)

    Morishima, Naohito; Yagi, Ryo; Shimizu, Kazuhiko; Ota, Susumu

    2013-10-01

    This study evaluated the prognostic factors of synkinesis following Bell's palsy and Ramsay Hunt syndrome. A total of 345 patients consisting of 309 cases of Bell's palsy and 36 cases of Ramsay Hunt syndrome were enrolled in our study. The following 13 factors were considered as candidate prognostic factors for the presence of synkinesis at 6 months from onset: age, sex, diagnosis, diabetes mellitus, initial onset or recurrence, electroneurography (ENoG), number of days from onset to first visit to our hospital, the lowest Yanagihara grading system score, the change in Yanagihara score after 1 month, otalgia, hearing loss, vertigo and taste disturbances. These factors were analyzed by logistic regression. Logistic regression analysis clarified the lowest Yanagihara score, the change in Yanagihara score after 1 month, and the ENoG value for a prognosis of synkinesis. The most predictive prognostic factor was the lowest Yanagihara score, and the adjusted odds ratio in the multivariate model was 11.415. As for other prognostic factors, the adjusted odds ratios ranged from 7.017 (ENoG value) to 8.310 (the change in Yanagihara score after 1 month). These findings were therefore considered as high risk factors for synkinesis. It is possible to predict synkinesis following Bell's palsy and Ramsay Hunt syndrome on the basis of clinical symptoms. The lowest Yanagihara score, and the change in Yanagihara score after 1 month, together with the ENoG value at the onset, were found to be especially important factors for predicting synkinesis following Bell's palsy and Ramsay Hunt syndrome. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Prognostic Value and Development of a Scoring System in Horses With Systemic Inflammatory Response Syndrome

    OpenAIRE

    Roy, M.?F.; Kwong, G.P.S.; Lambert, J.; Massie, S.; Lockhart, S.

    2017-01-01

    Background Despite its widespread use in equine medicine, the clinical value of the systemic inflammatory response syndrome (SIRS) concept in horses remains unknown. Objectives To study the prognostic value of measures of SIRS in horses and identify the best model of severe SIRS to predict outcome. Animals A total of 479 consecutive adult horse emergency admissions to a private primary referral practice. Methods Prospective observational study. All adult horses admitted for emergency treatmen...

  12. Urinary Angiotensinogen Could Be a Prognostic Marker of the Renoprotection of Olmesartan in Metabolic Syndrome Patients.

    Science.gov (United States)

    Mizushige, Tomoko; Kobori, Hiroyuki; Hitomi, Hirofumi; Nishijima, Yoko; Tomoda, Fumihiro; Morimoto, Satoshi; Kohno, Masakazu; Nishiyama, Akira

    2016-10-27

    This study was performed to demonstrate urinary angiotensinogen as a potential prognostic marker of the albuminuria reduction effects of olmesartan in patients with metabolic syndrome. In 24 patients (eight women, 57.88 ± 2.00 years), 5-40 mg/day of olmesartan were given. Urinary concentrations of albumin and angiotensinogen (normalized by urinary concentrations of creatinine) and plasma renin activity were measured before and after the 12- and 24-week marks of olmesartan treatment. Olmesartan treatment increased plasma renin activity and decreased urinary albumin and urinary angiotensinogen significantly ( p metabolic syndrome.

  13. Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

    Science.gov (United States)

    Matute-Blanch, Clara; Villar, Luisa M; Álvarez-Cermeño, José C; Rejdak, Konrad; Evdoshenko, Evgeniy; Makshakov, Gleb; Nazarov, Vladimir; Lapin, Sergey; Midaglia, Luciana; Vidal-Jordana, Angela; Drulovic, Jelena; García-Merino, Antonio; Sánchez-López, Antonio J; Havrdova, Eva; Saiz, Albert; Llufriu, Sara; Alvarez-Lafuente, Roberto; Schroeder, Ina; Zettl, Uwe K; Galimberti, Daniela; Ramió-Torrentà, Lluís; Robles, René; Quintana, Ester; Hegen, Harald; Deisenhammer, Florian; Río, Jordi; Tintoré, Mar; Sánchez, Alex; Montalban, Xavier; Comabella, Manuel

    2018-04-01

    The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid

  14. [Hematologic response predictor factors in adults with myelodysplastic syndromes (SMD) treated with cyclosporin A (CSA)].

    Science.gov (United States)

    Zamora-Pérez, Elia; López-Karpovitch, Xavier

    2015-01-01

    Myelodysplastic syndromes (MDS) are clonal diseases of hematopoietic cells. The International Prognostic Scoring System (IPSS) is the risk scale most employed in MDS. Cyclosporin A (CsA) has been used in the treatment of cytopenias in MDS. To evaluate hematologic response and identify response predictive factors in adults with MDS treated with CsA. Patients with MDS diagnosed according World Health Organization (WHO) classification were recruited from January 1997 to June 2012. All patients were classified with IPSS, IPSS revised (IPSS-R),WHO Prognostic Scoring System (WPSS), and WPSS revised (WPSS-R) risk scales. Cyclosporin A was administered orally at a dose of 5 mg/kg/day. Hematologic response was evaluated following the International Working Group for MDS (2006 version) criteria. Inclusion criteria were met by 32 patients. Median age was 56.5 years, with a median follow-up of 3.1 years. Hematologic response was 56.2% and erythrocyte independence transfusion was found in 42.9% of patients. Age,hemoglobin level, and WPSS at diagnosis were independent predictive factors for CsA response. Survival was longer in responder than in nonresponder CsA patients (p=0.06). Cyclosporin A induced hematologic response in >50% of patients with MDS aged <57 years, with Hb<8 g/dl and low WPSS at diagnosis.

  15. Prognostic significance of Wilms tumor 1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Kobayashi, Sumiko; Ueda, Yasunori; Nannya, Yasuhito; Shibayama, Hirohiko; Tamura, Hideto; Ogata, Kiyoyuki; Akatsuka, Yoshiki; Usuki, Kensuke; Ito, Yoshikazu; Okada, Masaya; Suzuki, Takahiro; Hata, Tomoko; Matsuda, Akira; Tohyama, Kaoru; Kakumoto, Keiji; Koga, Daisuke; Mitani, Kinuko; Naoe, Tomoki; Sugiyama, Haruo; Takaku, Fumimaro

    2016-03-31

    This present study was designed to follow up 82 patients among 115 MDS patients registered in study ODK-0801 for 5 years, to analyze the relationship between the WT1 mRNA expression level and prognosis. This study aimed to investigate the clinical utility of WT1 mRNA expression levels. After study ODK-0801, we investigated the conditions of the same patients once a year, including any clinical and laboratory findings supporting the diagnosis, and treatment among the living patients. When we assessed the survival time of 82 MDS patients by WT1 mRNA expression level, there were significant differences between the eukemia (AML) transformation indicated that a high WT1 mRNA expression level (> 104 copies/μ g RNA) was a strong prognostic factor for a short time to AML transformation. The results indicate that the tumorigenesis of MDS is likely to originate at the stem cell level, suggesting that the WT1 mRNA level measurement in the BM is an effective prognostic marker in patients with MDS.

  16. Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

    NARCIS (Netherlands)

    MC Langemeijer, Saskia; Mariani, Niccolo; Knops, Ruth; Gilissen, Christian; Woestenenk, Rob; de Witte, Theo; Huls, Gerwin; van der Reijden, Bert A.; Jansen, Joop H.

    2016-01-01

    Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially

  17. Azacitidine-lenalidomide (ViLen) combination yields a high response rate in higher risk myelodysplastic syndromes (MDS)-ViLen-01 protocol.

    Science.gov (United States)

    Mittelman, Moshe; Filanovsky, Kalman; Ofran, Yishai; Rosenbaum, Hanna; Raanani, Pia; Braester, Andrei; Goldschmidt, Neta; Kirgner, Ilya; Herishanu, Yair; Perri, Chava; Ellis, Martin; Oster, Howard S

    2016-10-01

    Azacitidine treatment is effective in higher risk MDS (HR-MDS), with less than 50 % response, lasting 2 years. Aza and lenalidomide (Len) have a potential synergistic effect. ViLen-01 phase IIa trial includes 6-month induction (Aza 75 mg/m(2)/day, days 1-5, Len 10 mg/day, days 6-21, every 28 days), 6-month consolidation (Aza 75 mg/m(2)/day, days 1-5, every 28 days), and 12-month maintenance (Len 10 mg/day, days 1-21, every 28 days). Response was evaluated according to IWG criteria. Totally, 25 patients enrolled, with an average of 76.3 years old (60-87), and 88 % with major comorbidities. Thirteen patients completed induction, 7 proceeded for consolidation, and 2 for maintenance. The overall response rate (ORR) was 72 % (18/25), with 6 (24 %) for CR, 3 (12 %) for marrow CR, and 9 (36 %) for hematologic improvement (HI). The 7 non-responding patients were on the study 3 days to 4.1 months. At 6 months, 4 of 6 evaluable patients achieved complete cytogenetic response and 2 with del (5q) at diagnosis. Adverse events (AEs) were as expected in these patients: grades III-IV, mainly hematologic-thrombocytopenia (20 patients) and neutropenia (13 patients). The common non-hematologic AEs were infections (14 patients), nausea (7), vomiting (7), diarrhea (7), and skin reactions (5). The median progression-free survival (PFS) was 12 ± 1.36 months, with median overall survival (OS) of 12 ± 1.7 months. Quality of life (FACT questionnaire) data were available for 12 patients with a tendency towards improved QoL. This trial with elderly HR-MDS patients with an expected poor prognosis demonstrates a high (72 %) response rate and a reasonable expected safety profile but a relatively short PFS and OS.

  18. Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model.

    Science.gov (United States)

    Stoddart, Angela; Wang, Jianghong; Hu, Chunmei; Fernald, Anthony A; Davis, Elizabeth M; Cheng, Jason X; Le Beau, Michelle M

    2017-06-01

    There is accumulating evidence that functional alteration(s) of the bone marrow (BM) microenvironment contribute to the development of some myeloid disorders, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In addition to a cell-intrinsic role of WNT activation in leukemia stem cells, WNT activation in the BM niche is also thought to contribute to the pathogenesis of MDS and AML. We previously showed that the Apc -haploinsufficient mice ( Apc del/+ ) model MDS induced by an aberrant BM microenvironment. We sought to determine whether Apc, a multifunctional protein and key negative regulator of the canonical β-catenin (Ctnnb1)/WNT-signaling pathway, mediates this disease through modulating WNT signaling, and whether inhibition of WNT signaling prevents the development of MDS in Apc del/+ mice. Here, we demonstrate that loss of 1 copy of Ctnnb1 is sufficient to prevent the development of MDS in Apc del/+ mice and that altered canonical WNT signaling in the microenvironment is responsible for the disease. Furthermore, the US Food and Drug Administration (FDA)-approved drug pyrvinium delays and/or inhibits disease in Apc del /+ mice, even when it is administered after the presentation of anemia. Other groups have observed increased nuclear CTNNB1 in stromal cells from a high frequency of MDS/AML patients, a finding that together with our results highlights a potential new strategy for treating some myeloid disorders. © 2017 by The American Society of Hematology.

  19. Age-related epigenetic drift in the pathogenesis of MDS and AML.

    Science.gov (United States)

    Maegawa, Shinji; Gough, Sheryl M; Watanabe-Okochi, Naoko; Lu, Yue; Zhang, Nianxiang; Castoro, Ryan J; Estecio, Marcos R H; Jelinek, Jaroslav; Liang, Shoudan; Kitamura, Toshio; Aplan, Peter D; Issa, Jean-Pierre J

    2014-04-01

    The myelodysplastic syndrome (MDS) is a clonal hematologic disorder that frequently evolves to acute myeloid leukemia (AML). Its pathogenesis remains unclear, but mutations in epigenetic modifiers are common and the disease often responds to DNA methylation inhibitors. We analyzed DNA methylation in the bone marrow and spleen in two mouse models of MDS/AML, the NUP98-HOXD13 (NHD13) mouse and the RUNX1 mutant mouse model. Methylation array analysis showed an average of 512/3445 (14.9%) genes hypermethylated in NHD13 MDS, and 331 (9.6%) genes hypermethylated in RUNX1 MDS. Thirty-two percent of genes in common between the two models (2/3 NHD13 mice and 2/3 RUNX1 mice) were also hypermethylated in at least two of 19 human MDS samples. Detailed analysis of 41 genes in mice showed progressive drift in DNA methylation from young to old normal bone marrow and spleen; to MDS, where we detected accelerated age-related methylation; and finally to AML, which markedly extends DNA methylation abnormalities. Most of these genes showed similar patterns in human MDS and AML. Repeat element hypomethylation was rare in MDS but marked the transition to AML in some cases. Our data show consistency in patterns of aberrant DNA methylation in human and mouse MDS and suggest that epigenetically, MDS displays an accelerated aging phenotype.

  20. Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome.

    Science.gov (United States)

    Wang, Chen; Su, Wei; Cai, Qian-Qian; Cai, Hao; Ji, Wei; Di, Qian; Duan, Ming-Hui; Cao, Xin-Xin; Zhou, Dao-Bin; Li, Jian

    2016-07-01

    POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain (HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis (P = 0.021; hazard ratio [HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival (P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Prognostic factors of Bell's palsy and Ramsay Hunt syndrome

    Science.gov (United States)

    Cai, Zhengyi; Li, Huijing; Wang, Xun; Niu, Xiaoting; Ni, Peiqi; Zhang, Wanli; Shao, Bei

    2017-01-01

    Abstract The aim of this study was to compare clinical characteristics, electroneurography (ENoG) results, and functional outcomes of patients with Bell's palsy (BP) and Ramsay Hunt syndrome (RHS). Around 57 patients with BP and 23 patients with RHS were enrolled in this study from January 2010 and September 2015. Both clinical characteristics and ENoG results were recorded at hospital admission. The evaluations of functional outcomes were conducted with House–Brackmann (H-B) grading system at 6-month follow-up. There were no significant differences in age, gender proportion, initial H-B grades, time before commencement of treatment and the presence of comorbid disease in 2 groups. However, the final H-B grades at 6-month follow-up were significantly better in BP patients than RHS patients. The results of ENoG showed that degeneration index (DI) was significantly higher in the RHS group than the BP group. But no significant difference was found in the value of prolonged latency time (PLT) between the 2 groups. In multivariate analysis, age and ENoG DI were independently associated with functional outcome of recovery in the BP group (OR 0.167, 95% CI 0.038–0.622, P = 0.009 and OR 0.289 95% CI 0.107–0.998, P = 0.050, respectively). However, in the RHS group, only ENoG DI was related to the final H-B grades (OR 0.067, 95% CI 0.005–0.882, P = 0.040). Spearman's rank correlation analysis showed that higher age and ENoG DI were related to poorer prognosis in 2 groups (P < 0.05). PLT was related to functional outcomes only in the BP group (rs = 0.460, P < 0.001). The receiver operating characteristic (ROC) of ENoG DI analysis revealed that the cutoff value was 67.0% for BP prognosis and 64.5% for RHS prognosis. What's more, patients with hypertension or diabetes mellitus had both higher final H-B grade and ENoG DI than those without the same comorbidity. Patients with RHS had poorer prognosis than those with BP. Some factors including age

  2. [Cardio-hepatic Syndrome in Heart Failure: Prevalence, Pathogenesis and Prognostic Significance].

    Science.gov (United States)

    Kobalava, Zh D; Villevalde, S V; Soloveva, A E

    2016-12-01

    In a framework of the concept of organ interactions great attention has been paid during recent years to interaction of the heart and liver. The term cardio-hepatic syndrome (CHS) designates the combination of clinical-laboratory signs of liver dysfunction and acute or chronic cardiac pathology. In this article, we present mechanisms and characteristics of CHS in acute and chronic heart failure (HF), data of large clinical studies and registries on prevalence, associations, and prognostic significance of cardiogenic disturbances of liver function in patients with HF.

  3. PD-1 signaling and inhibition in AML and MDS.

    Science.gov (United States)

    Haroun, Faysal; Solola, Sade A; Nassereddine, Samah; Tabbara, Imad

    2017-09-01

    Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.

  4. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells.

    Science.gov (United States)

    Geyh, S; Oz, S; Cadeddu, R-P; Fröbel, J; Brückner, B; Kündgen, A; Fenk, R; Bruns, I; Zilkens, C; Hermsen, D; Gattermann, N; Kobbe, G; Germing, U; Lyko, F; Haas, R; Schroeder, T

    2013-09-01

    Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.

  5. A Prognostic Model for Development of Profound Shock among Children Presenting with Dengue Shock Syndrome.

    Directory of Open Access Journals (Sweden)

    Phung Khanh Lam

    Full Text Available To identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS.We analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was "profound DSS", defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock, or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock, and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches.The analysis population included 1207 children of whom 222 (18% progressed to "profound DSS" and 433 (36% had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for "profound DSS" showed acceptable discrimination (AUC=0.69 for internal validation and calibration and is presented as a simple score-chart.Several risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas.

  6. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes.

    Science.gov (United States)

    Della Porta, Matteo Giovanni; Malcovati, Luca; Boveri, Emanuela; Travaglino, Erica; Pietra, Daniela; Pascutto, Cristiana; Passamonti, Francesco; Invernizzi, Rosangela; Castello, Alessandro; Magrini, Umberto; Lazzarino, Mario; Cazzola, Mario

    2009-02-10

    We studied bone marrow (BM) histologic abnormalities in myelodysplastic syndromes (MDS) classified according to WHO criteria to determine their clinical correlates and prognostic value. Three hundred one consecutive patients were retrospectively evaluated for BM fibrosis and CD34 immunoreactivity. Marrow fibrosis was assessed following the European consensus guidelines. Moderate to severe BM fibrosis was detected in 17% of cases and was associated with multilineage dysplasia (P = .001), high transfusion requirement (P WHO categories with excess of blasts (P according to International Prognostic Scoring System and WHO classification-based Prognostic Scoring System categories, BM fibrosis involved a shift to a one-step more advanced risk group. BM fibrosis identifies a distinct subgroup of MDS with multilineage dysplasia, high transfusion requirement, and poor prognosis and represents an independent prognostic factor that may be useful in clinical decision making. Furthermore, the presence of CD34+ cell clusters is an independent risk factor for progression to acute leukemia.

  7. Urinary Angiotensinogen Could Be a Prognostic Marker of the Renoprotection of Olmesartan in Metabolic Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Tomoko Mizushige

    2016-10-01

    Full Text Available This study was performed to demonstrate urinary angiotensinogen as a potential prognostic marker of the albuminuria reduction effects of olmesartan in patients with metabolic syndrome. In 24 patients (eight women, 57.88 ± 2.00 years, 5–40 mg/day of olmesartan were given. Urinary concentrations of albumin and angiotensinogen (normalized by urinary concentrations of creatinine and plasma renin activity were measured before and after the 12- and 24-week marks of olmesartan treatment. Olmesartan treatment increased plasma renin activity and decreased urinary albumin and urinary angiotensinogen significantly (p < 0.05. Based on the % change in urinary albumin, patients were divided into two groups, responders (<−50% and non-responders (≥−50%, and a logistic analysis of urinary angiotensinogen before treatment showed the area under the curve as 0.694. When the cutoff value of urinary angiotensinogen before the treatment of 13.9 µg/g Cr was used, the maximum Youden index (0.500, specificity: 11/12 = 91.7% and sensitivity: 7/12 = 58.3% was obtained. When all patients were re-divided into two groups, those with higher values of urinary angiotensinogen before the treatment (Group H, n = 16 and those with lower values, Group H showed significantly decreased urinary albumin (p < 0.05. Therefore, urinary angiotensinogen could be a prognostic marker of the albuminuria reduction effects of olmesartan in patients with metabolic syndrome.

  8. MDS 3.0 Frequency Report

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MDS 3.0 Frequency Report summarizes information for active residents currently in nursing homes. The source of these counts is the residents MDS assessment...

  9. The Differencies in Adult and Pediatric Myelodysplastic Syndrome: A Review

    Directory of Open Access Journals (Sweden)

    Vasekova P

    2016-08-01

    Full Text Available Myelodysplastic syndrome (MDS represent very heterogenous group of clonal stem cell bone marrow disorders with ineffective haematopoesis leading to cytopenias in peripheral blood and increased risk of blastic transformation and evolution of acute myeloid leukemia. MDS is a disease of older age mostly, in children it seems to be very rare. There are several significant morphological, cytogenetic and prognostic differencies of the disease in adults and in children. Adult MDS patients most commonly manifest with symptoms of anemia, bleeding and infection are uncommon. In childhood, MDS manifests predominantly by neutropenia and thrombocytopenia. In addition, some pediatric MDS patients present also with constitutional disease’s signs and symptoms. Early and correct diagnosis in both age groups is essential for the choice of appropriate therapy and also for next life of patients. However, the diagnosis of MDS is challenging, complex and requiring close correlation of clinical symptoms, laboratory parameters and standardized examination of BM biopsies. The authors present an overview focused on biology of MDS in adults and children, on the differences in the incidence, clinical presentation and treatment. They summarize the possibilities and limits of histopathological diagnosis and differential diagnosis of the disease in different age groups. A major problem in the morphological diagnosis of MDS remains the determination, whether the myelodysplasia is due to clonal disorder. It might result also from some other factors, as significant dysplasia can also occur in reactive conditions, and vice versa, only discrete dysplasia is sometimes observed in MDS patients. Although histomorphological and immunohistochemical analysis of BM biopsy is invasive and time-consuming examination, it has its value in the diagnosis, differential diagnosis and evaluation of therapeutic effect.

  10. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database.

    Science.gov (United States)

    Shukron, Ofir; Vainstein, Vladimir; Kündgen, Andrea; Germing, Ulrich; Agur, Zvia

    2012-09-01

    One-third of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML), with its concomitant poor prognosis. Recently, multiple mutations have been identified in association with MDS-to-sAMLtransition, but it is still unclear whether all these mutations are necessary for transformation. If multiple independent mutations are required for the transformation, sAML risk should increase with time from MDS diagnosis. In contrast, if a single critical biological event determines sAML transformation; its risk should be constant in time elapsing from MDS diagnosis. To elucidate this question, we studied a database of 1079 patients with MDS. We classified patients according to the International Prognostic Scoring System (IPSS), using either the French-American-British (FAB) or the World Health Organization (WHO) criteria, and statistically analyzed the resulting transformation risk curves of each group. The risk of transformation after MDS diagnosis remained constant in time within three out of four risk groups, and in all four risk groups, when patients were classified according to FAB or to the WHO-determined criteria, respectively. Further subdivision by blast percentage or cytogenetics had no influence on this result. Our analysis suggests that a single random biological event leads to transformation to sAML, thus calling for the exclusion of time since MDS diagnosis from the clinical decision-making process. Copyright © 2012 Wiley Periodicals, Inc.

  11. New MDS or near MDS self-dual codes over finite fields

    OpenAIRE

    Tong, Hongxi; Wang, Xiaoqing

    2016-01-01

    The study of MDS self-dual codes has attracted lots of attention in recent years. There are many papers on determining existence of $q-$ary MDS self-dual codes for various lengths. There are not existence of $q-$ary MDS self-dual codes of some lengths, even these lengths $< q$. We generalize MDS Euclidean self-dual codes to near MDS Euclidean self-dual codes and near MDS isodual codes. And we obtain many new near MDS isodual codes from extended negacyclic duadic codes and we obtain many new M...

  12. Gene expression profiling in MDS and AML: potential and future avenues

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, K; Boultwood, J; Ferrari, S

    2011-01-01

    Today, the classification systems for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) already incorporate cytogenetic and molecular genetic aberrations in an attempt to better reflect disease biology. However, in many MDS/AML patients no genetic aberrations have been identified yet...... the MDS/AML classification system, incorporating as yet unknown molecular genetic and epigenetic pathomechanisms, which are likely reflected by aberrant gene expression patterns. In this study, we provide a comprehensive review on how GEP has contributed to a refined molecular taxonomy of MDS and AML...... technologies, which will continue to improve our understanding of malignant transformation in myeloid malignancies and thereby contribute to individualized risk-adapted treatment strategies for MDS and AML patients....

  13. Does C-reactive Protein Add Prognostic Value to GRACE Score in Acute Coronary Syndromes?

    International Nuclear Information System (INIS)

    Correia, Luis Cláudio Lemos; Vasconcelos, Isis; Garcia, Guilherme; Kalil, Felipe; Ferreira, Felipe; Silva, André; Oliveira, Ruan; Carvalhal, Manuela; Freitas, Caio; Noya-Rabelo, Márcia Maria

    2014-01-01

    The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score

  14. Does C-reactive Protein Add Prognostic Value to GRACE Score in Acute Coronary Syndromes?

    Energy Technology Data Exchange (ETDEWEB)

    Correia, Luis Cláudio Lemos, E-mail: lccorreia@terra.com.br; Vasconcelos, Isis; Garcia, Guilherme; Kalil, Felipe; Ferreira, Felipe; Silva, André; Oliveira, Ruan; Carvalhal, Manuela; Freitas, Caio; Noya-Rabelo, Márcia Maria [Escola Bahiana de Medicina e Saúde Pública, Salvador, BA (Brazil); Hospital São Rafael, Salvador, BA (Brazil)

    2014-05-15

    The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score.

  15. Sleep/Wake Modulation of Polysomnographic Patterns has Prognostic Value in Pediatric Unresponsive Wakefulness Syndrome.

    Science.gov (United States)

    Molteni, Erika; Avantaggiato, Paolo; Formica, Francesca; Pastore, Valentina; Colombo, Katia; Galbiati, Sara; Arrigoni, Filippo; Strazzer, Sandra

    2016-08-15

    Sleep patterns of pediatric patients in unresponsive wakefulness syndrome (UWS) have been poorly investigated, and the prognostic potential of polysomnography (PSG) in these subjects is still uncertain. The goal of the study was to identify quantitative PSG indices to be applied as possible prognostic markers in pediatric UWS. We performed PSG in 27 children and adolescents with UWS due to acquired brain damage in the subacute phase. Patients underwent neurological examination and clinical assessment with standardized scales. Outcome was assessed after 36 mo. PSG tracks were scored for sleep stages and digitally filtered. The spectral difference between sleep and wake was computed, as the percent difference at specific spectral frequencies. We computed (1) the ratio between percent power in the delta and alpha frequency bands, (2) the ratio between alpha and theta frequency bands, and (3) the power ratio index, during wake and sleep, as proposed in previous literature. The predictive role of several clinical and PSG measures was tested by logistic regression. Correlation was found between the differential measures of electroencephalographic activity during sleep and wake in several frequency bands and the clinical scales (Glasgow Outcome Score, Level of Cognitive Functioning Assessment Scale, and Disability Rating Scale) at follow-up; the Sleep Patterns for Pediatric Unresponsive Wakefulness Syndrome (SPPUWS) scores correlated with the differential measures, and allowed outcome prediction with 96.3% of accuracy. The differential measure of electroencephalographic activity during sleep and wake in the beta band and, more incisively, SPPUWS can help in determining the capability to recover from pediatric UWS well before the confirmation provided by suitable clinical scales. © 2016 American Academy of Sleep Medicine.

  16. Genetic Testing in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Nardi, Valentina; Hasserjian, Robert P

    2016-03-01

    Cytogenetic analysis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is essential for disease diagnosis, classification, prognostic stratification, and treatment guidance. Molecular genetic analysis of CEBPA, NPM1, and FLT3 is already standard of care in patients with AML, and mutations in several additional genes are assuming increasing importance. Mutational analysis of certain genes, such as SF3B1, is also becoming an important tool to distinguish subsets of MDS that have different biologic behaviors. It is still uncertain how to optimally combine karyotype with mutation data in diagnosis and risk-stratification of AML and MDS, particularly in cases with multiple mutations and/or several mutationally distinct subclones. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Prognostic Value of Geriatric Conditions Beyond Age After Acute Coronary Syndrome.

    Science.gov (United States)

    Sanchis, Juan; Ruiz, Vicente; Bonanad, Clara; Valero, Ernesto; Ruescas-Nicolau, Maria Arantzazu; Ezzatvar, Yasmin; Sastre, Clara; García-Blas, Sergio; Mollar, Anna; Bertomeu-González, Vicente; Miñana, Gema; Núñez, Julio

    2017-06-01

    The aim of the present study was to investigate the prognostic value of geriatric conditions beyond age after acute coronary syndrome. This was a prospective cohort design including 342 patients (from October 1, 2010, to February 1, 2012) hospitalized for acute coronary syndrome, older than 65 years, in whom 5 geriatric conditions were evaluated at discharge: frailty (Fried and Green scales), comorbidity (Charlson and simple comorbidity indexes), cognitive impairment (Pfeiffer test), physical disability (Barthel index), and instrumental disability (Lawton-Brody scale). The primary end point was all-cause mortality. The median follow-up for the entire population was 4.7 years (range, 3-2178 days). A total of 156 patients (46%) died. Among the geriatric conditions, frailty (Green score, per point; hazard ratio, 1.11; 95% CI, 1.02-1.20; P=.01) and comorbidity (Charlson index, per point; hazard ratio, 1.18; 95% CI, 1.0-1.40; P=.05) were the independent predictors. The introduction of age in a basic model using well-established prognostic clinical variables resulted in an increase in discrimination accuracy (C-statistic=.716-.744; P=.05), though the addition of frailty and comorbidity provided a nonsignificant further increase (C-statistic=.759; P=.36). Likewise, the addition of age to the clinical model led to a significant risk reclassification (continuous net reclassification improvement, 0.46; 95% CI, 0.21-0.67; and integrated discrimination improvement, 0.04; 95% CI, 0.01-0.09). However, the addition of frailty and comorbidity provided a further significant risk reclassification in comparison to the clinical model with age (continuous net reclassification improvement, 0.40; 95% CI, 0.16-0.65; and integrated discrimination improvement, 0.04; 95% CI, 0.01-0.10). In conclusion, frailty and comorbidity are mortality predictors that significantly reclassify risk beyond age after acute coronary syndrome. Copyright © 2017 Mayo Foundation for Medical Education and

  18. T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

    DEFF Research Database (Denmark)

    Vries, A.C. de; Langerak, A.W.; Verhaaf, B.

    2008-01-01

    (Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which...

  19. Hematologic, clinical, and cytogenetic analysis in 109 patients with primary myelodysplastic syndrome. Prognostic significance of morphology and chromosome findings.

    Science.gov (United States)

    Parlier, V; van Melle, G; Beris, P; Schmidt, P M; Tobler, A; Haller, E; Bellomo, M J

    1994-12-01

    One hundred and nine patients with primary myelodysplastic syndrome (MDS) were classified according to the French-American-British (FAB) criteria: 27 refractory anemia (RA, 25%), 26 RA with ringed sideroblasts (RARS, 24%), 16 RA with excess of blasts (RAEB, 15%), 10 RAEB in transformation (RAEB-t, 9%), 25 chronic myelomonocytic leukemia (CMMoL, 23%), and five unclassifiable MDS (4%). Forty-three were women and 66 were men (sex ratio 2:3). Age ranged from 30-92 years (mean 69 years) with nine patients aged less than 50 years (8%). A cytogenetic result was obtained in all cases. At initial study, a chromosome defect was observed in 56% of patients. Rates of abnormality depended on FAB subtype: 52% in RA, 100% in RA 5q-, 50% in RARS, 56% in RAEB, 70% in RAEB-t and 44% in CMMoL. The most frequent single defects were del(5q), -7/del(7q), del(20q), Y loss, and +8. Except for the 5q- syndrome entity, specific chromosome defects were not associated with particular FAB subtypes. Bone marrow (BM) insufficiency (22%) and leukemic transformation (21%) were the most important causes of death. The rate of leukemic transformation increased with the number of dysplastic BM cell lineages and was also associated with karyotype complexity and the proportion of abnormal/normal metaphases. The longest median survivals were observed in RARS (142 months) and RA/RA5q- (91 months) types. Median survivals decreased with increasing Bournemouth score values. Patients with three abnormal cell lineages had a median survival shorter than those with one or two abnormal lineages. Similarly, patients with complex defects had shorter survival than those with single or double defects or a normal karyotype. There was no statistically significant difference between survival of NN (normal), AN (abnormal/normal), and AA patients or between survival of patients with del(5q), -7/del(7q), +8 or del(20q).

  20. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults.

    Science.gov (United States)

    Savona, Michael R; Malcovati, Luca; Komrokji, Rami; Tiu, Ramon V; Mughal, Tariq I; Orazi, Attilio; Kiladjian, Jean-Jacques; Padron, Eric; Solary, Eric; Tibes, Raoul; Itzykson, Raphael; Cazzola, Mario; Mesa, Ruben; Maciejewski, Jaroslaw; Fenaux, Pierre; Garcia-Manero, Guillermo; Gerds, Aaron; Sanz, Guillermo; Niemeyer, Charlotte M; Cervantes, Francisco; Germing, Ulrich; Cross, Nicholas C P; List, Alan F

    2015-03-19

    Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation. © 2015 by The American Society of Hematology.

  1. Epigenetically Aberrant Stroma in MDS Propagates Disease via Wnt/β-Catenin Activation.

    Science.gov (United States)

    Bhagat, Tushar D; Chen, Si; Bartenstein, Matthias; Barlowe, A Trevor; Von Ahrens, Dagny; Choudhary, Gaurav S; Tivnan, Patrick; Amin, Elianna; Marcondes, A Mario; Sanders, Mathijs A; Hoogenboezem, Remco M; Kambhampati, Suman; Ramachandra, Nandini; Mantzaris, Iaonnis; Sukrithan, Vineeth; Laurence, Remi; Lopez, Robert; Bhagat, Prafullla; Giricz, Orsi; Sohal, Davendra; Wickrema, Amittha; Yeung, Cecilia; Gritsman, Kira; Aplan, Peter; Hochedlinger, Konrad; Yu, Yiting; Pradhan, Kith; Zhang, Jinghang; Greally, John M; Mukherjee, Siddhartha; Pellagatti, Andrea; Boultwood, Jacqueline; Will, Britta; Steidl, Ulrich; Raaijmakers, Marc H G P; Deeg, H Joachim; Kharas, Michael G; Verma, Amit

    2017-09-15

    The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine-treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/β-catenin activation signature in CD34 + cells from advanced cases of MDS, where it associated with adverse prognosis. Constitutive activation of β-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98-HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment, which lead to β-catenin activation and disease progression of MDS. Cancer Res; 77(18); 4846-57. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group.

    Science.gov (United States)

    Cseh, Annamaria M; Niemeyer, Charlotte M; Yoshimi, Ayami; Catala, Albert; Frühwald, Michael C; Hasle, Henrik; van den Heuvel-Eibrink, Mary M; Lauten, Melchior; De Moerloose, Barbara; Smith, Owen P; Bernig, Toralf; Gruhn, Bernd; Kulozik, Andreas E; Metzler, Markus; Olcay, Lale; Suttorp, Meinolf; Furlan, Ingrid; Strahm, Brigitte; Flotho, Christian

    2016-03-01

    Low-dose azacitidine is efficient and safe in the therapy of malignant myeloid disorders in adults but data in children are lacking. We present a retrospective analysis of 24 children and young adults with myelodysplastic syndrome (MDS) who received azacitidine at the time of first diagnosis or relapse after allotransplant (2 children were treated with azacitidine both initially and for relapse). Diagnoses were refractory cytopenia of childhood (N = 4), advanced primary MDS (N = 9) and secondary MDS (N = 11). The median duration of treatment was four cycles. Azacitidine was well tolerated, but cytopenias led to dose reduction in five cases. Treatment was discontinued in one child because of impaired renal function. Sixteen MDS patients were treated with azacitidine at first diagnosis. One complete clinical remission was observed and one child showed complete marrow remission; six children experienced stable disease with haematological improvement. Ten children received azacitidine for relapsed MDS after transplant: of these, seven experienced stable disease for 2-30 cycles (median 3), including one patient with haematological improvement for seven cycles. In summary, azacitidine is effective in some children with MDS and appears to be a non-toxic option in palliative situations to prolong survival. © 2016 John Wiley & Sons Ltd.

  3. [Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors].

    Science.gov (United States)

    Calderón Romero, María; Arce Portillo, Elena; López Lobato, Mercedes; Muñoz Cabello, Beatriz; Blanco Martínez, Bárbara; Madruga Garrido, Marcos; Alonso Luego, Olga

    2017-12-06

    West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  4. Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

    Science.gov (United States)

    Ruppenthal, Sabrina; Kleiner, Helga; Nolte, Florian; Fabarius, Alice; Hofmann, Wolf-Karsten; Nowak, Daniel; Seifarth, Wolfgang

    2018-01-01

    ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. Aberrant expression and/or altered separase proteolytic activity are associated with centrosome amplification, aneuploidy, tumorigenesis and disease progression. Since centrosome alterations are a common and early detectable feature in patients with myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role in disease risk stratification, we examined separase activity on single cell level in 67 bone marrow samples obtained from patients with MDS, secondary acute myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy controls by a flow cytometric separase activity assay. The separase activity distribution (SAD) value, a calculated measure for the occurrence of cells with prominent separase activity within the analyzed sample, was tested for correlation with the centrosome, karyotype and gene mutation status. We found higher SAD values in bone marrow cells of sAML patients than in corresponding cells of MDS patients. This concurred with an increased incidence of aberrant centrosome phenotypes in sAML vs. MDS samples. No correlation was found between SAD values and the karyotype/gene mutation status. During follow-up of four MDS patients we observed increasing SAD values after transformation to sAML, in two patients SAD values decreased during azacitidine therapy. Cell culture experiments employing MDS-L cells as an in vitro model of MDS revealed that treatment with rigosertib, a PLK1 inhibitor and therapeutic drug known to induce G2/M arrest, results in decreased SAD values. In conclusion, the appearance of cells with unusual high separase activity levels, as indicated by increased SAD values, concurs with the transformation of MDS to sAML and may reflect separase dysregulation potentially contributing to clonal evolution during MDS progression. Separase activity measurement may therefore be useful as a

  5. Outcomes and prognostic factors of surgical treatments for brachycephalic obstructive airway syndrome in 3 breeds.

    Science.gov (United States)

    Liu, Nai-Chieh; Oechtering, Gerhard U; Adams, Vicki J; Kalmar, Lajos; Sargan, David R; Ladlow, Jane F

    2017-02-01

    To determine prognostic indicators for the surgical treatment of brachycephalic obstructive airway syndrome (BOAS) and to compare the prognosis of 2 multilevel surgical procedures. Prospective clinical study. Client-owned pugs, French bulldogs, and bulldogs (n = 50). Noninvasive whole-body barometric plethysmography (WBBP) was used to assess respiratory function before, 1 month and 6 months after upper airway corrective surgery. Postoperatively, BOAS indices (ie, ascending severity score generated from WBBP data, 0%-100%) that equaled to or exceeded the cut-off values of BOAS in the diagnostic models were considered to have a "poor prognosis." A multivariate logistic regression was used to assess predictors for prognosis. The median BOAS indices decreased after surgery (from 76% to 63%, P dogs with indices in this range would still be considered clinically affected. Age (odds ratios [OR] = 0.96, 95% confidence interval [CI]: 0.93-0.99, P dogs with a higher probability of poor prognosis. © 2017 The American College of Veterinary Surgeons.

  6. Serum Uric Acid Level as a Prognostic Marker in Patients With Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Lee, Hyun Woo; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Lee, Sang-Min

    2017-01-01

    Uric acid acts as both a pathogenic inflammatory mediator and an antioxidative agent. Several studies have shown that uric acid level correlates with the incidence, severity, and prognosis of pulmonary diseases. However, the association between uric acid level and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how serum uric acid level is related with clinical prognosis of ARDS. A retrospective cohort study with propensity score matching was conducted at a medical intensive care unit of a tertiary teaching hospital. The medical records of patients diagnosed with ARDS admitted from 2005 through 2011 were reviewed. Two hundred thirty-seven patients with ARDS met the inclusion criteria. Patients with a serum uric acid level uric acid group, and those with a level ≥3 mg/dL were classified into the normal to high uric acid group. We selected 40 patients in each group using propensity score matching. A higher percentage of patients in the low uric acid group experienced clinical improvement in ARDS. More patients died from sepsis in the normal to high uric acid group. Kaplan-Meier analysis showed that a low serum uric acid level was significantly associated with better survival rate. In patients with ARDS, a low serum uric acid level may be a prognostic marker of a low risk of in-hospital mortality.

  7. Prognostic utility of vitamin D in acute coronary syndrome patients in coastal Norway.

    Science.gov (United States)

    Naesgaard, Patrycja A; Pönitz, Volker; Aarsetoey, Hildegunn; Brügger-Andersen, Trygve; Grundt, Heidi; Harris, William S; Staines, Harry; Nilsen, Dennis W T

    2015-01-01

    An inverse relationship between cardiovascular risk and levels of vitamin D and omega-3 index may exist. To evaluate the prognostic utility of serum 25-hydroxyvitamin D [25(OH)D] in 871 patients with suspected acute coronary syndrome (ACS) and to assess the seasonal correlation between 25(OH)D and the omega-3 index in 456 ACS patients from southwestern Norway. In the univariate analysis the hazard ratio (HR) at 2-year follow-up for all-cause mortality in the highest as compared to the lowest quartile of 25(OH)D in the total population was 0.61 (95% confidence interval (CI), 0.37-1.00), P = 0.050. At 7-year follow-up, the corresponding HR for all-cause mortality was 0.66 (95% CI, 0.49-0.90), P = 0.008, and for females alone 0.51 (95% CI, 0.32-0.83), P = 0.006. Quartile survival did not differ in the multivariable analysis, whereas 25(OH)D omega-3 index, were noted, and the two biomarkers were positively correlated, especially during winter-spring; Pearson's correlation coefficient was 0.358, P omega-3 index.

  8. Metabolic syndrome in peritoneal dialysis patients: choice of diagnostic criteria and prognostic implications.

    Science.gov (United States)

    Szeto, Cheuk-Chun; Kwan, Bonnie Ching-Ha; Chow, Kai-Ming; Leung, Chi-Bon; Cheng, Mei-Shan; Law, Man-Ching; Li, Philip Kam-Tao

    2014-04-01

    In the general population, metabolic syndrome (MES) is associated with cardiovascular risk. However, the definition of MES and its prognostic implication among patients undergoing peritoneal dialysis (PD) remain controversial. We studied 329 prevalent PD patients from April 2008 to April 2011 and compared four sets of diagnostic criteria: the original World Health Organization (WHO) criteria, the International Diabetes Federation (IDF) criteria, the original National Cholesterol Education Program (NCEP) criteria, and the modified NCEP criteria. Nutritional status, body composition, and arterial pulse-wave velocity were measured. Patients were followed for 31.7 ± 15.5 months. Among the 329 patients, 175 (53.2%) fulfilled the WHO criteria, 177 (53.8%) the IDF criteria, 199 (60.5%) the original NCEP criteria, and 218 (66.3%) the modified NCEP criteria. The agreement among the four sets of criteria was fair to moderate (Cohen κ=0.35-0.58). Patients with MES defined by all four criteria had higher adipose tissue mass than the others, although the difference in adipose tissue mass was most pronounced with the IDF criteria (MES versus no MES, 18.2 ± 7.9 versus 10.7 ± 5.9 kg; Pdefinition or clinical scoring system for risk stratification of PD patients.

  9. Prognostic Usefulness of Low Ischemic Risk SPECT in non-ST Segment Elevation Acute Coronary Syndromes

    International Nuclear Information System (INIS)

    Castillo Costa, Yanina; Mauro, Victor; Perez, Roberto; Charask, Adrian; Fairman, Enrique; Gomez Santamaria, Hector; Goral, Jorge; Barrero, Carlos

    2009-01-01

    Background: Myocardial perfusion imaging tests are used for the clinical assessment of patients hospitalized with non-ST segment elevation acute coronary syndromes (NSTACS) who have favorable in-hospital outcomes with medical therapy. However, the prognostic relevance of a .low ischemic risk. (LR) single photon emission computed tomography (SPECT) in patients with NSTACS managed with a conservative approach is uncertain, as most of the information derives from patients with chronic coronary artery disease. Objectives: 1) To analyze the outcomes of patients with NSTACS and LR SPECT at discharge, 2) to compare the results of a normal SPECT with transient perfusion defects (TPDs), permanent perfusion defects (PPDs) or combined defects (CDs), and 3) to determine the additional value of SPECT to classic risk variables. Material and Methods: Patients admitted to the CCU with a NSTACS were included. Follow-up was continued during 12 months. Definitions: Clinical risk based on TIMI risk score. LR SPECT (under exercise or pharmacological stress): TPDs ≤ 3/17 segments, PPDs ≤ 3/17 segments, CPDs: TPDs + PPDs and normal: absence of defects. Clinical events (CEs): death/infarction or rehospitalization due to angina. Results: A total of 137 patients were included (median age 59 years, 60% were men). A low TIMI risk score was present in 54% of patients and 46% presented a moderate risk. CE: 5.8%. The incidence of clinical events related to perfusion defects was as follows: normal: 2.1%, TPD: 4.5%, PPD: 5.9% and CPD: 25% (p [es

  10. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets.

    Science.gov (United States)

    Gleason, Michelle K; Ross, Julie A; Warlick, Erica D; Lund, Troy C; Verneris, Michael R; Wiernik, Andres; Spellman, Stephen; Haagenson, Michael D; Lenvik, Alexander J; Litzow, Mark R; Epling-Burnette, Pearlie K; Blazar, Bruce R; Weiner, Louis M; Weisdorf, Daniel J; Vallera, Daniel A; Miller, Jeffrey S

    2014-05-08

    Myelodysplastic syndromes (MDS) are stem cell disorders that can progress to acute myeloid leukemia. Although hematopoietic cell transplantation can be curative, additional therapies are needed for a disease that disproportionally afflicts the elderly. We tested the ability of a CD16xCD33 BiKE to induce natural killer (NK) cell function in 67 MDS patients. Compared with age-matched normal controls, CD7(+) lymphocytes, NK cells, and CD16 expression were markedly decreased in MDS patients. Despite this, reverse antibody-dependent cell-mediated cytotoxicity assays showed potent degranulation and cytokine production when resting MDS-NK cells were triggered with an agonistic CD16 monoclonal antibody. Blood and marrow MDS-NK cells treated with bispecific killer cell engager (BiKE) significantly enhanced degranulation and tumor necrosis factor-α and interferon-γ production against HL-60 and endogenous CD33(+) MDS targets. MDS patients had a significantly increased proportion of immunosuppressive CD33(+) myeloid-derived suppressor cells (MDSCs) that negatively correlated with MDS lymphocyte populations and CD16 loss on NK cells. Treatment with the CD16xCD33 BiKE successfully reversed MDSC immunosuppression of NK cells and induced MDSC target cell lysis. Lastly, the BiKE induced optimal MDS-NK cell function irrespective of disease stage. Our data suggest that the CD16xCD33 BiKE functions against both CD33(+) MDS and MDSC targets and may be therapeutically beneficial for MDS patients.

  11. Clinical and biological implications of driver mutations in myelodysplastic syndromes.

    Science.gov (United States)

    Papaemmanuil, Elli; Gerstung, Moritz; Malcovati, Luca; Tauro, Sudhir; Gundem, Gunes; Van Loo, Peter; Yoon, Chris J; Ellis, Peter; Wedge, David C; Pellagatti, Andrea; Shlien, Adam; Groves, Michael John; Forbes, Simon A; Raine, Keiran; Hinton, Jon; Mudie, Laura J; McLaren, Stuart; Hardy, Claire; Latimer, Calli; Della Porta, Matteo G; O'Meara, Sarah; Ambaglio, Ilaria; Galli, Anna; Butler, Adam P; Walldin, Gunilla; Teague, Jon W; Quek, Lynn; Sternberg, Alex; Gambacorti-Passerini, Carlo; Cross, Nicholas C P; Green, Anthony R; Boultwood, Jacqueline; Vyas, Paresh; Hellstrom-Lindberg, Eva; Bowen, David; Cazzola, Mario; Stratton, Michael R; Campbell, Peter J

    2013-11-21

    Myelodysplastic syndromes (MDS) are a heterogeneous group of chronic hematological malignancies characterized by dysplasia, ineffective hematopoiesis and a variable risk of progression to acute myeloid leukemia. Sequencing of MDS genomes has identified mutations in genes implicated in RNA splicing, DNA modification, chromatin regulation, and cell signaling. We sequenced 111 genes across 738 patients with MDS or closely related neoplasms (including chronic myelomonocytic leukemia and MDS-myeloproliferative neoplasms) to explore the role of acquired mutations in MDS biology and clinical phenotype. Seventy-eight percent of patients had 1 or more oncogenic mutations. We identify complex patterns of pairwise association between genes, indicative of epistatic interactions involving components of the spliceosome machinery and epigenetic modifiers. Coupled with inferences on subclonal mutations, these data suggest a hypothesis of genetic "predestination," in which early driver mutations, typically affecting genes involved in RNA splicing, dictate future trajectories of disease evolution with distinct clinical phenotypes. Driver mutations had equivalent prognostic significance, whether clonal or subclonal, and leukemia-free survival deteriorated steadily as numbers of driver mutations increased. Thus, analysis of oncogenic mutations in large, well-characterized cohorts of patients illustrates the interconnections between the cancer genome and disease biology, with considerable potential for clinical application.

  12. [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

    Science.gov (United States)

    Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

    2015-06-01

    To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

  13. [Systemic inflammatory response syndrome as prognostic indicator in hospitalized cirrhotic patients].

    Science.gov (United States)

    Machaca Quea, Nancy Roxana; Salazar Ventura, Sonia; Montes Teves, Pedro

    2014-07-01

    The systemic inflammation worsens circulatory disorders in cirrhotic patients and recently the systemic inflammatory response syndrome (SIRS) may be a prognostic indicator therein. The aim of the study was to determine whether the presence of SIRS at admission in hospitalized cirrhotic patients is associated with complications or mortality. A retrospective cohorts study was conducted at the Daniel Alcides Carrion National Hospital.Hospitalized cirrhotic patients admitted from July 2008 to December 2010 without significant comorbidities, malignancy,HIV infection, or stay less than 72 hours were included. Presence of SIRS at admission and the occurrence of complications or death after 72 hours of admission were evaluated. 150 cirrhotic patients were admitted, six were excluded;three for lower survival at 72 hours, one for neoplasia, one for severe heart failure and two for chronic renal failure. One hundred forty four patients were included, 95 (66%) patients had SIRS at admission. There was no significant difference in age, sex, etiology, in both groups. SIRS was associated with higher scores of MELD and Child-Turcotte Pugh. Of the group of patients with SIRS, 41 (43%) had complications and 16 (16.8%) died, while the group without SIRS 5 (10.2%) had complications and two (4%) died p < 0.0001 and p=0.028 respectively. The most common complications were infections and hepatic encephalopathy. In multivariate analysis SIRS was associated with complications (p < 0.006) but not with mortality(p < 0.276). SIRS is common in hospitalized cirrhotic patients and is associated with in-hospital complications.

  14. Clinical Spectrum, Therapeutic Outcomes, and Prognostic Predictors in Sjogren's Syndrome-associated Neuropathy.

    Science.gov (United States)

    Sivadasan, Ajith; Muthusamy, Karthik; Patel, Bimal; Benjamin, Rohit Ninan; Prabhakar, A T; Mathew, Vivek; Aaron, Sanjith; Alexander, Mathew

    2017-01-01

    There are limited data regarding long-term follow-up and therapeutic outcomes in Sjogren's syndrome (SS)-associated peripheral neuropathy. In this study, we aim to study the clinical, electrophysiological spectrum and therapeutic responses among the different subtypes of SS-associated neuropathy. The predictors of suboptimal treatment response will be identified. The study included a retrospective cohort of patients with SS-associated neuropathy between January 2012 and November 2015. Baseline clinical, laboratory, electrophysiological data and details of treatment were noted. Therapeutic outcomes were assessed at follow-up and compared among the different subtypes. Prognostic predictors were determined using logistic regression analysis. Fifty-four patients were included in the study. Sensory ataxic neuropathy (17, including 9 with sensory ganglionopathy) and radiculoneuropathy (11) were the main subtypes. Notable atypical presentations included acute neuropathies, pure motor neuropathies, and hypertrophic neuropathy. Concomitant autoimmune disorders were present in 24 (44.4%) patients. Most presentations were subacute-chronic (51, 94.4%). Minor salivary gland biopsy had a higher yield compared to serological markers (81.5 vs. 44.4%). Sensory ataxic neuropathy was associated with greater severity and autonomic dysfunction. Improvement was noted in 33 (61%) patients. Cranial neuropathy and radiculoneuropathy subtypes were associated with the best treatment responses. Chronicity, orthostatic hypotension, baseline severity, and marked axonopathy (nerve biopsy) were predictive of a suboptimal therapeutic response. The study highlights the heterogeneous spectrum, atypical presentations, and differential therapeutic responses. SS-associated neuropathy remains underdiagnosed. Early diagnosis and prompt initiation of immunotherapy before worsening axonal degeneration is paramount. SS-associated neuropathy need not necessarily be associated with a poor prognosis.

  15. Prognostic Utility of Vitamin D in Acute Coronary Syndrome Patients in Coastal Norway

    Directory of Open Access Journals (Sweden)

    Patrycja A. Naesgaard

    2015-01-01

    Full Text Available Background. An inverse relationship between cardiovascular risk and levels of vitamin D and omega-3 index may exist. Objectives. To evaluate the prognostic utility of serum 25-hydroxyvitamin D [25(OHD] in 871 patients with suspected acute coronary syndrome (ACS and to assess the seasonal correlation between 25(OHD and the omega-3 index in 456 ACS patients from southwestern Norway. Results. In the univariate analysis the hazard ratio (HR at 2-year follow-up for all-cause mortality in the highest as compared to the lowest quartile of 25(OHD in the total population was 0.61 (95% confidence interval (CI, 0.37–1.00, P=0.050. At 7-year follow-up, the corresponding HR for all-cause mortality was 0.66 (95% CI, 0.49–0.90, P=0.008, and for females alone 0.51 (95% CI, 0.32–0.83, P=0.006. Quartile survival did not differ in the multivariable analysis, whereas 25(OHD < 40 nM (<16 ng/mL was found to be independently related to mortality. Seasonal differences in 25(OHD, but not for the omega-3 index, were noted, and the two biomarkers were positively correlated, especially during winter-spring; Pearson’s correlation coefficient was 0.358, P<0.001. Conclusion. Vitamin D levels are related to survival, especially in females, and correlate with the omega-3 index.

  16. A meta-analysis on the prognostic significance of inferolateral early repolarization pattern in Brugada syndrome.

    Science.gov (United States)

    Georgopoulos, Stamatis; Letsas, Konstantinos P; Liu, Tong; Kalafateli, Maria; Korantzopoulos, Panagiotis; Bürkle, Gerd; Vlachos, Konstantinos; Giannopoulos, Georgios; Efremidis, Michael; Deftereos, Spyridon; Sideris, Antonios; Takagi, Masahiko; Yan, Gan-Xin; Ehrlich, Joachim R

    2018-01-01

    The early repolarization (ER) pattern has been linked to an increased risk for arrhythmic death in various clinical settings. There are limited and conflicting data regarding the prognostic significance of ER pattern in Brugada syndrome (BS). The aim of this meta-analysis was to provide a detailed analysis of the currently available studies regarding the arrhythmic risk in patients with BS and ER pattern. Current databases were searched until May 2015. A random-effect meta-analysis of the effect of ER pattern on the incidence of arrhythmic events in patients with BS was performed. Five studies were included comprising a total of 1375 patients with BS. An ER pattern was reported in 177 patients (12.8%). During follow-up (44.9-93 months), 143 patients (10.4%) suffered an arrhythmic event. Overall, BS patients with ER pattern displayed an increased risk of arrhythmic events compared to patients without ER (OR 3.29, 95% CI: 2.06 to 5.26, P pattern location. Inferior, lateral, or inferolateral ER pattern location was observed in 20.3%, 32.2%, and 48%, respectively. An inferolateral ER location conferred the higher arrhythmic risk (OR 4.87, 95% CI: 2.64 to 9.01, Ppattern is associated with a high risk of arrhythmic events in patients with BS. In particular, BS patients with inferolateral ER (global ER pattern) displayed the highest arrhythmic risk. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  17. Therapy-related AML/MDS after treatment of low-grade B-cell lymphoma

    International Nuclear Information System (INIS)

    Yanada, Masamitsu

    2008-01-01

    Described is the therapy-related AML (acute myelogenetic leukemia)/MDS (myelo-dysplasia syndrome), which is manifested after various treatments of low-grade B-cell lymphoma and has strongly attracted attention because of the markedly improved prognosis due to recent advantages of the therapy for the disease. AML/MDS occurs several years after chemotherapy and/or radiation therapy which cause DNA damage in hematopoietic cells, and the AML/MDS risk is known increased in patients undergone especially with autologous transplantation of those cells. AML/MDS has the feature similar to that caused either by alkylating agent or by topoisomerase-2 inhibitor, and the disease by radiation belong to the former. Yet unclear is the problem whether malignant cells causing the disease after therapy are derived from the remaining cells in the graft or in the body. Although irradiations of total body and total lymphaden as well as chemotherapy are said to be related to AML/MDS and local irradiation does not contribute to its risk, the most important factor for the disease is considered to be the autotransplantation as the recurrence occurs in 50% after it. Thus the treatment history should be taken into consideration for suppressing AML/MDS, for which follow up with consideration for the disease is required particularly after autotransplantation. (R.T.)

  18. Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS.

    Science.gov (United States)

    Mei, Y; Zhao, B; Basiorka, A A; Yang, J; Cao, L; Zhang, J; List, A; Ji, P

    2018-04-01

    Anemia is characteristic of myelodysplastic syndromes (MDS). The mechanisms of anemia in MDS are unclear. Using a mouse genetic approach, here we show that dual deficiency of mDia1 and miR-146a, encoded on chromosome 5q and commonly deleted in MDS (del(5q) MDS), causes an age-related anemia and ineffective erythropoiesis mimicking human MDS. We demonstrate that the ageing bone marrow microenvironment is important for the development of ineffective erythropoiesis in these mice. Damage-associated molecular pattern molecules (DAMPs), whose levels increase in ageing bone marrow, induced TNFα and IL-6 upregulation in myeloid-derived suppressor cells (MDSCs) in mDia1/miR-146a double knockout mice. Mechanistically, we reveal that pathologic levels of TNFα and IL-6 inhibit erythroid colony formation and differentially affect terminal erythropoiesis through reactive oxygen species-induced caspase-3 activation and apoptosis. Treatment of the mDia1/miR-146a double knockout mice with all-trans retinoic acid, which promoted the differentiation of MDSCs and ameliorated the inflammatory bone marrow microenvironment, significantly rescued anemia and ineffective erythropoiesis. Our study underscores the dual roles of the ageing microenvironment and genetic abnormalities in the pathogenesis of ineffective erythropoiesis in del(5q) MDS.

  19. The differentiation and prognostic implication of the solitary colonic polyp and the polyposis syndromes: A radiologic, histologic, and pathologic approach

    International Nuclear Information System (INIS)

    Olmsted, W.W.; Lichtenstein, J.E.

    1987-01-01

    The differential diagnosis of the solitary colonic polyp and the implications and prognostic significance of the solitary colonic polyp and the polyposis syndromes are frequently confusing because of imprecise and overlapping terminology. Such confusion may lead to misdiagnosis or overdiagnosis and improper patient treatment and surveillance. In the first part of this course, basic terms are defined to acquaint all participants with current common ground. The most frequently occurring solitary polyps (e.g., the colonic adenoma, hyperplastic polyp, Peutz-Jeghers hamartoma, juvenile hamartoma, and inflammatory polyp) are illustrated in detail with radiologic-histologic-pathologic correlation. The prognostic significance of each type of lesion and a scheme for proper colonic surveillance is discussed. In the second part of the session, there is a thorough discussion of multiple colonic polyps and the polyposis syndromes. Radiologic-pathologic correlation are used to illustrate these entities, and therapeutic and diagnostic implications are thoroughly covered. The differential diagnosis of the polyposis syndromes, including lymphoid abnormalities, pneumatosis intestinalis, and colitis cystica profunda, are mentioned. The participant should expect to gain a full understanding of the solitary and multiple colonic polyp states and algorithms for prognosis and treatment

  20. Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML

    NARCIS (Netherlands)

    S. Hirabayashi (Shinsuke); C. Flotho (Christian); J. Moetter (Jessica); M. Heuser (Michael); H. Hasle (Henrik); B. Gruhn (Bernd); T. Klingebiel (Thomas); F. Thol (Felicitas); B. Schlegelberger (Brigitte); I. Baumann (Irith); B. Strahm (Brigitte); J. Stary (Jan); F. Locatelli (Franco); M. Zecca (Marco); E. Bergstraesser (Eva); M.N. Dworzak (Michael); M.M. van den Heuvel-Eibrink (Marry); B. de Moerloose (Barbara); S. Ogawa (Susumu); C.M. Niemeyer (Charlotte); M. Wlodarski (Marcin)

    2012-01-01

    textabstractSomatic mutations of the spliceosomal machinery occur frequently in adult patients with myelodysplastic syndrome (MDS). We resequenced SF3B1, U2AF35, and SRSF2 in 371 children with MDS or juvenile myelomonocytic leukemia. We found missense mutations in 2 juvenile myelomonocytic leukemia

  1. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  2. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients

    DEFF Research Database (Denmark)

    Ørskov, A. D.; Treppendahl, M. B.; Skovbo, A.

    2015-01-01

    The hypomethylating agents (HMAs) are standard therapy for patients with higher-risk myelodysplastic syndrome (MDS); however, the majority of the patients will lose their response to HMAs over time due to unknown mechanisms. It has recently been shown that T cell expression of the immunoinhibitory......-responding patients compared to healthy controls (p = 0.023). Accordingly, in addition to their beneficial function, HMAs induce PD-1 expression on T cells in the MDS microenvironment, thereby likely hampering the immune response against the MDS blasts. Thus, we suggest that activation of the PD-1 checkpoint during...

  3. Hypotéza o MDS kódech

    OpenAIRE

    Kesely, Michal

    2010-01-01

    In this thesis, we study some properties of MDS codes and we mainly focus on the MDS codes conjecture. In the first chapter we define MDS codes, show some examples and basic properties of MDS codes, for example a link between MDS codes and Latin squares or rectangles. Afterwards we state the MDS codes conjecture and prove it in several cases. In the third chapter we can observe the relationship between MDS codes and narcs in projective geometries. Finally we present those known cases, for whi...

  4. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS).

    Science.gov (United States)

    Malcovati, Luca; Della Porta, Matteo G; Strupp, Corinna; Ambaglio, Ilaria; Kuendgen, Andrea; Nachtkamp, Kathrin; Travaglino, Erica; Invernizzi, Rosangela; Pascutto, Cristiana; Lazzarino, Mario; Germing, Ulrich; Cazzola, Mario

    2011-10-01

    Anemia is an established negative prognostic factor in myelodysplastic syndromes but the relationship between its degree and clinical outcome is poorly defined. We, therefore, studied the relationship between severity of anemia and outcome in myelodysplastic syndrome patients. We studied 840 consecutive patients diagnosed with myelodysplastic syndromes at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, and 504 patients seen at the Heinrich-Heine-University Hospital, Düsseldorf, Germany. Hemoglobin levels were monitored longitudinally and analyzed by means of time-dependent Cox's proportional hazards regression models. Hemoglobin levels lower than 9 g/dL in males (HR 5.56, P=0.018) and 8 g/dL in females (HR=5.35, P=0.026) were independently related to reduced overall survival, higher risk of non-leukemic death and cardiac death (Panemia, defined as hemoglobin below these thresholds, was found to be as effective as transfusion-dependency in the prognostic assessment. After integrating this definition of severe anemia into the WHO classification-based Prognostic Scoring System, time-dependent regression and landmark analyses showed that the refined model was able to identify risk groups with different survivals at any time during follow up. Accounting for severity of anemia through the WHO classification-based Prognostic Scoring System provides an objective criterion for prognostic assessment and implementation of risk-adapted treatment strategies in myelodysplastic syndrome patients.

  5. Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center

    Directory of Open Access Journals (Sweden)

    Narayanan S

    2017-02-01

    Full Text Available Santhosh Narayanan Department of Medicine, Government Medical College, Kozhikode, Kerala, India Background: Myelodysplastic syndrome (MDS, a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce.Objectives: (1 To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2 to study its progression to acute myeloid leukemia (AML in the selected patients over the study period.Methods: A prospective observational study was performed with patients from Department of Medicine and Hematology, Government Medical College, Kozhikode, who were diagnosed with MDS within the study period (from 1 January 2014 to 31 July 2015. Secondary causes of dysplasia were excluded. In possible cases, the international prognostic scoring system was followed. These patients were followed up for an additional 6 months to assess the progression of MDS to AML based on symptoms, signs, hemogram, or repeat peripheral smear/bone marrow studies.Results: Of the 60 patients, 73% were aged >60 years. Disease was common in males, with a male:female ratio of 7:3. Thirty-five percent of the patients were working in agricultural and allied fields and had pesticide exposure. Patients with prior radiation exposure had significant association with adverse outcome. Fatigue was the prominent symptom and was reported by 90% of the patients. Blasts were >5% in peripheral smear; bone marrow cytopenia and dysplasia at the time of diagnosis had significant association with risk of transforming to AML. Refractory anemia (RA, observed in 22 patients, was the most common type of MDS. Most of the patients with RA with excess blasts type-1 and RA with excess blasts type-2 transformed to AML

  6. [Myelodysplastic syndrome--classification, prognosis and therapy].

    Science.gov (United States)

    Cermák, J; Michalová, K; Vítek, A

    2002-09-22

    The impact of classification, prognostic factors and treatment on survival and rate of leukemic transformation was analysed in 197 patients with primary myelodysplastic syndrome (MDS) treated in the Institute of Hematology and Blood Transfusion in the years 1980-2000. The patients were classified according to the FAB criteria and divided into risk groups according to the International Prognostic Scoring System (IPSS). A separate evaluation of 34 patients who underwent stem cell transplantation and of 163 of those not transplanted was performed. Median survival of not transplanted patients with RAEB (10.0 months) and RAEB-T (12.0 months) was significantly shorter than survival of RA (62.4 months) and RARS (48.1 months, P MDS when compared with supportive care. On the contrary, median survival of transplanted patients with RAEB and RAEB-T was 38.4 months in comparison to 11.5 months in those not transplanted (P MDS. Stem cell transplantation had a significant beneficial effect on survival of patients with RAEB or RAEB-T as well as of patients included in intermediate II. or high risk subgroups. The impact of stem cell transplantation on survival of patients with RA or with low or intermediate I. risk was not significant. Therefore, further criteria should be taken in account for indication of stem cell transplantation in these subgroups of patients.

  7. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine.

    Science.gov (United States)

    Sébert, Marie; Komrokji, Rami S; Sekeres, Mikkael A; Prebet, Thomas; Cluzeau, Thomas; Santini, Valeria; Gyan, Emmanuel; Sanna, Alessandro; Ali, Najla HAl; Hobson, Sean; Eclache, Virginie; List, Alan; Fenaux, Pierre; Adès, Lionel

    2017-12-01

    Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (pcytogenetics. CyR was achieved in 32% of the 281 evaluable patients with abnormal cytogenetics, was complete (CCyR) in 71 (25.3%) patients. We found no correlation between hematological response and cytogenetic response and 21% of the patients with CCyR did not achieve morphological response. In the 281 patients, we found no impact of CyR on survival, but when restricting to MDS (ie: <20% marrow blasts) achievement of CCyR was associated with better OS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Myelodysplastic and myeloproliferative neoplasms: updates on the overlap syndromes.

    Science.gov (United States)

    Thota, Swapna; Gerds, Aaron T

    2018-04-01

    Myelodysplastic and myeloproliferative neoplasms (MDS/MPN) is a rare and distinct group of myeloid neoplasms with overlapping MDS and MPN features. Next generation sequencing studies have led to an improved understanding of MDS/MPN disease biology by identifying recurrent somatic mutations. Combining the molecular findings to patho-morphologic features has improved the precision of diagnosis and prognostic models in MDS/MPN. We discuss and highlight these updates in MDS/MPN nomenclature and diagnostic criteria per revised 2016 WHO classification of myeloid neoplasms in this article. There is an ongoing effort for data integration allowing for comprehensive genomic characterization, development of improved prognostic tools, and investigation for novel therapies using an international front specific for MDS/MPN. In this article, we discuss updates in prognostic models and current state of treatment for MDS/MPN.

  9. Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance.

    Science.gov (United States)

    de Swart, Louise; Smith, Alex; MacKenzie, Marius; Symeonidis, Argiris; Neukirchen, Judith; Mikulenková, Dana; Vallespí, Teresa; Zini, Gina; Paszkowska-Kowalewska, Malgorzata; Kruger, Anton; Saft, Leonie; Fenaux, Pierre; Bowen, David; Hellström-Lindberg, Eva; Čermák, Jaroslav; Stauder, Reinhard; Tatic, Aurelia; Holm, Mette Skov; Malcovati, Luca; Mądry, Krzysztof; Droste, Jackie; Blijlevens, Nicole; de Witte, Theo; Germing, Ulrich

    2017-07-01

    The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3-9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.

  10. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance.

    Science.gov (United States)

    Kwok, Brian; Hall, Jeff M; Witte, John S; Xu, Yin; Reddy, Prashanti; Lin, Keming; Flamholz, Rachel; Dabbas, Bashar; Yung, Aine; Al-Hafidh, Jenan; Balmert, Emily; Vaupel, Christine; El Hader, Carlos; McGinniss, Matthew J; Nahas, Shareef A; Kines, Julie; Bejar, Rafael

    2015-11-19

    Establishing a diagnosis in patients suspected of having a myelodysplastic syndrome (MDS) can be challenging and could be informed by the identification of somatic mutations. We performed a prospective study to examine the frequency and types of mutations encountered in 144 patients with unexplained cytopenias. Based on bone marrow findings, 17% were diagnosed with MDS, 15% with idiopathic cytopenias of undetermined significance (ICUS) and some evidence of dysplasia, and 69% with ICUS and no dysplasia. Bone marrow DNA was sequenced for mutations in 22 frequently mutated myeloid malignancy genes. Somatic mutations were identified in 71% of MDS patients, 62% of patients with ICUS and some dysplasia, and 20% of ICUS patients and no dysplasia. In total, 35% of ICUS patients carried a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis. We validated these results in a cohort of 91 lower-risk MDS and 249 ICUS cases identified over a 6-month interval. Mutations were found in 79% of those with MDS, in 45% of those with ICUS with dysplasia, and in 17% of those with ICUS without dysplasia. The spectrum of mutated genes was similar with the exception of SF3B1 which was rarely mutated in patients without dysplasia. Variant allele fractions were comparable between clonal ICUS (CCUS) and MDS as were mean age and blood counts. We demonstrate that CCUS is a more frequent diagnosis than MDS in cytopenic patients. Clinical and mutational features are similar in these groups and may have diagnostic utility once outcomes in CCUS patients are better understood. © 2015 by The American Society of Hematology.

  11. SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.

    Science.gov (United States)

    Inoue, D; Kitaura, J; Matsui, H; Hou, H-A; Chou, W-C; Nagamachi, A; Kawabata, K C; Togami, K; Nagase, R; Horikawa, S; Saika, M; Micol, J-B; Hayashi, Y; Harada, Y; Harada, H; Inaba, T; Tien, H-F; Abdel-Wahab, O; Kitamura, T

    2015-04-01

    Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (SETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-β signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS.

  12. Telomere dynamics in patients with del (5q) MDS before and under treatment with lenalidomide.

    Science.gov (United States)

    Beier, Fabian; Masouleh, Behzad Kharabi; Buesche, Guntram; Ventura Ferreira, Monica S; Schneider, Rebekka K; Ziegler, Patrick; Wilop, Stefan; Vankann, Lucia; Gattermann, Norbert; Platzbecker, Uwe; Giagounidis, Aristoteles; Götze, Katharina S; Nolte, Florian; Hofmann, Wolf-Karsten; Haase, Detlef; Kreipe, Hans; Panse, Jens; Blasco, Maria A; Germing, Ulrich; Brümmendorf, Tim H

    2015-09-21

    Myelodysplastic syndrome (MDS) associated with an acquired, isolated deletion of chromosome 5q (del (5q) MDS), represent a clonal disorder of hematopoiesis and a clinically distinct entity of MDS. Treatment of del (5q) MDS with the drug lenalidomide has significantly improved quality of life leading to transfusion independence and complete cytogenetic response rates (CCR) in the majority of patients. Telomeres are located at the end of eukaryotic chromosomes and are linked to replicative history/potential as well as genetic (in) stability of hematopoietic stem cells. Here, we analyzed telomere length (TL) dynamics before and under lenalidomide treatment in the peripheral blood and/or bone marrow of del (5q) patients enrolled in the LEMON-5 study (NCT01081431). Hematopoietic cells from del (5q) MDS patients were characterized by significantly shortened TL compared to age-matched healthy controls. Telomere loss was more accelerated in patients with longer disease duration (>2 years) and more pronounced cytopenias. Sequential analysis under lenalidomide treatment revealed that previously shortened TL in peripheral blood cells was significantly "elongated" towards normal levels within the first six months suggesting a shift from clonal del (5q) cells towards normal hematopoiesis in lenalidomide treated MDS patients. Taken together our findings suggest that the development of the del (5q) clone is associated with accelerated telomere shortening at diagnosis. However, upon induction of CCR and reoccurrence of normal hematopoiesis, the lack of a persistent TL deficit argues against telomere-mediated genetic instability neither as a disease-promoting event of del (5q) MDS nor for lenalidomide mediated development of secondary primary malignancies of the hematopoietic system in responding patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Current State of the Art: Management of Higher Risk Myelodysplastic Syndromes.

    Science.gov (United States)

    Komrokji, Rami S

    2016-08-01

    The higher risk myelodysplastic syndrome (MDS) patients, defined by the International Prognostic Scoring System (IPSS) as intermediate-2 or high-risk groups, compromise a third of MDS patients who have an expected survival of less than 1.5 years. Our ability to better define higher risk MDS improved with the proposal of new clinical risk models such as the revised IPSS and by integration of molecular data, including somatic gene mutations. Allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only curative option. In higher risk MDS patients, proceeding early with AHSCT is associated with maximum survival gain. The decision to pursue AHSCT is individualized according to disease risk, comorbidities, and functional status. The role of therapy before AHSCT remains controversial, and the role of post-AHSCT maintenance is evolving. Hypomethylating agents are the only medications that alter the natural history of the disease. Azacitidine is the only drug reported to improve overall survival in higher risk MDS patients. Appropriate use and assessment of response is key for assuring patients benefit of such limited options. Treatment after failure of hypomethylating agents is an unmet need. The role of detectable somatic gene mutations in prognosis and tailoring therapy continue to emerge. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agents.

    Science.gov (United States)

    Odenike, Olatoyosi

    2017-12-08

    In the last decade, the treatment of higher-risk myelodysplastic syndromes (MDS) has revolved around the azanucleosides, azacitidine and decitabine, which at lower doses are postulated to work predominantly via their effects on inhibition of DNA methyltransferases and consequent DNA hypomethylation. For patients who relapse after, or do not respond to, hypomethylating agent therapy, the outcome is dismal, and new agents and approaches that have the potential to alter the natural history of these diseases are desperately needed. Allogeneic stem cell transplant is the only known potentially curative approach in MDS, but its applicability has been limited by the advanced age of patients and attendant comorbidities. There is now an increasing array of new agents under clinical investigation in MDS that aim to exploit our expanding understanding of molecular pathways that are important in the pathogenesis of MDS. This review focuses on a critical appraisal of novel agents being evaluated in higher-risk MDS that go beyond the conventional hypomethylating agent therapies approved by the US Food and Drug Administration. © 2016 by The American Society of Hematology. All rights reserved.

  15. A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome.

    Science.gov (United States)

    Garcia-Manero, Guillermo; Gartenberg, Gary; Steensma, David P; Schipperus, Martin R; Breems, Dimitri A; de Paz, Raquel; Valcárcel, David; Kranenburg, Britte; Reddy, Manjula; Komrokji, Rami S

    2014-09-01

    Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low- and intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2:1 ratio to siltuximab 15 mg kg(-1) every 4 weeks + best supportive care (BSC) or placebo + BSC for 12 weeks. The primary endpoint was reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as ≥50% relative decrease and ≥2-unit absolute decrease in RBC transfusions. Fifty and 26 patients were randomized to the siltuximab and placebo groups, respectively. The study did not meet its prespecified hypothesis, with six (12%) patients in the siltuximab group and one (3.8%) in the placebo group having reductions in RBC transfusions (P = 0.271). At the time of the planned futility analysis, the prespecified cutoff criteria were not met, and the study was terminated early due to lack of efficacy. No unexpected safety findings were observed. In conclusion, compared to placebo, treatment with siltuximab did not reduce RBC transfusions in transfusion-dependent patients with low- and intermediate-1-risk MDS. Future studies might explore siltuximab in patients with less iron overload and with elevated IL-6 levels and/or using higher doses for MDS. © 2014 Wiley Periodicals, Inc.

  16. Immune Mechanisms in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreas Glenthøj

    2016-06-01

    Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

  17. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Laura Guerenne

    2016-01-01

    Full Text Available Abstract Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS and acute myeloid leukemia (AML post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  18. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

    Science.gov (United States)

    Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia

    2016-01-27

    In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  19. Infant Attentional Behaviours as Prognostic Indicators in Cornelia-de-Lange Syndrome

    Science.gov (United States)

    Sarimski, Klaus

    2007-01-01

    Background: Cornelia-de-Lange syndrome is a rare congenital syndrome with poor social relatedness as one of several characteristics of its behavioural phenotype. Methods: Video observations were collected from seven children in their first year of life and again with age 2-4 years. Data were analysed for distribution of object-related and social…

  20. Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience.

    Science.gov (United States)

    Kantarjian, Hagop M; O'Brien, Susan; Huang, Xuelin; Garcia-Manero, Guillermo; Ravandi, Farhad; Cortes, Jorge; Shan, Jianqin; Davisson, Jan; Bueso-Ramos, Carlos E; Issa, Jean-Pierre

    2007-03-15

    Decitabine, a hypomethylating agent, is active and has been approved for the treatment of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia. Intensive chemotherapy is an accepted form of therapy for patients with higher risk MDS. The comparative efficacy of these 2 forms of treatment in MDS is unknown. The objective of the current study was to compare the efficacy and toxicity profiles of decitabine and intensive chemotherapy in MDS. The authors compared lower intensity decitabine therapy (n = 115 patients) with intensive chemotherapy (as it is used in acute myeloid leukemia [AML]) in patients with higher risk MDS. Two comparisons were made with a cohort of 376 historic patients (from 1995 to 2005): The first comparison included a subcohort of 115 patients (Group A) who matched the 115 decitabine study patients according to age, International Prognostic Scoring System, and cytogenetics; and the second comparison included the whole cohort of 376 patients without matching (Group B). A multivariate analysis was performed for outcome. The complete remission (CR) rate according to AML criteria was 43% with decitabine, 46% with intensive chemotherapy in Group A, and 52% with intensive chemotherapy in Group B. Compared with Group A, mortality at 6 weeks was 3% with decitabine versus 13% with intensive chemotherapy (P = .006) and, at 3 months, 7% with decitabine versus 23% with intensive chemotherapy (P = .001). Survival was better with decitabine versus intensive chemotherapy in Group A (median survival: 22 months vs 12 months; P accounting for the independent prognostic effect of pretreatment factors. In this analysis, decitabine was associated with a survival advantage compared with intensive chemotherapy in patients with higher risk MDS. Future studies should evaluate prospectively the results of decitabine versus intensive chemotherapy in this setting.

  1. Diagnostic and Prognostic Significance of DSM-5 Attenuated Psychosis Syndrome in Services for Individuals at Ultra High Risk for Psychosis.

    Science.gov (United States)

    Fusar-Poli, Paolo; De Micheli, Andrea; Cappucciati, Marco; Rutigliano, Grazia; Davies, Cathy; Ramella-Cravaro, Valentina; Oliver, Dominic; Bonoldi, Ilaria; Rocchetti, Matteo; Gavaghan, Lauren; Patel, Rashmi; McGuire, Philip

    2018-02-15

    The diagnostic and prognostic significance of the DSM-5-defined Attenuated Psychosis Syndrome (DSM-5-APS) in individuals undergoing an ultra high risk (UHR) clinical assessment for suspicion of psychosis risk is unknown. Prospective cohort study including all consecutive help-seeking individuals undergoing both a DSM-5-APS and a Comprehensive Assessment of At Risk Mental States (CAARMS 12/2006) assessment for psychosis risk at the Outreach and Support in South London (OASIS) UHR service (March 2013-April 2014). The diagnostic significance of DSM-5-APS was assessed with percent overall agreement, prevalence bias adjusted kappa, Bowker's test, Stuart-Maxwell test, residual analysis; the prognostic significance with Cox regression, Kaplan-Meier failure function, time-dependent area under the curve (AUC) and net benefits analysis. The impact of specific revisions of the DSM-5-APS was further tested. In 203 help-seeking individuals undergoing UHR assessment, the agreement between the DSM-5-APS and the CAARMS 12/2006 was only moderate (kappa 0.59). Among 142 nonpsychotic cases, those meeting DSM-5-APS criteria had a 5-fold probability (HR = 5.379) of developing psychosis compared to those not meeting DSM-5-APS criteria, with a 21-month cumulative risk of psychosis of 28.17% vs 6.49%, respectively. The DSM-5-APS prognostic accuracy was acceptable (AUC 0.76 at 24 months) and similar to the CAARMS 12/2006. The DSM-5-APS designation may be clinically useful to guide the provision of indicated interventions within a 7%-35% (2-year) range of psychosis risk. The removal of the criterion E or C of the DSM-5-APS may improve its prognostic performance and transdiagnostic value. The DSM-5-APS designation may be clinically useful in individuals accessing clinical services for psychosis prevention. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

  2. Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC).

    Science.gov (United States)

    DeZern, Amy E; Zeidan, Amer M; Barnard, John; Hand, Wesley; Al Ali, Najla; Brown, Francis; Zimmerman, Cassie; Roboz, Gail J; Garcia-Manero, Guillermo; Steensma, David P; Komrokji, Rami S; Sekeres, Mikkael A

    2017-06-01

    First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex. Female patients treated with DAC had a longer median OS (21.1 months, 95% CI: 16.0-28.0) than female patients treated with AZA (13.2 months, 95% CI: 11.0-15.9; p = .0014), while for males there was no significant difference between HMAs (median OS 18.3 months with DAC versus 17.9 months for AZA, p = .59). The biological reason for this variability is unclear, but may be a consequence of differences in cytidine deaminase activity between men and women.

  3. The emerging role of immune checkpoint based approaches in AML and MDS.

    Science.gov (United States)

    Boddu, Prajwal; Kantarjian, Hagop; Garcia-Manero, Guillermo; Allison, James; Sharma, Padmanee; Daver, Naval

    2018-04-01

    The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases. CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease. Immune checkpoint inhibition, specifically PD-1 inhibition, demonstrated limited single agent efficacy in patients with relapsed AML and with MDS post-hypomethylating therapy. Rationally designed combinations of PD-1 inhibitors with standard anti-leukemic therapy are needed. Hypomethylating agents such as azacitidine, up-regulate PD-1, PD-L1, and PD-L2 in patients with AML/MDS and up-regulation of these genes was associated with the emergence of resistance. The combination of azacitidine and PD-1/PD-L1 inhibition may be a potential mechanism to prevent or overcome resistance to 5-azacitidine. A number of such combinations are being evaluated in clinical trials with early encouraging results. Immune checkpoint inhibition is also an attractive option to improve relapse-free survival or eliminate minimal residual disease post induction and consolidation by enhancing T-cell surveillance in patients with high-risk AML. The ongoing clinical trials with checkpoint inhibitors in AML/MDS will improve our understanding of the immunobiology of these diseases and guide us to the most appropriate application of these agents in the therapy of AML/MDS.

  4. SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells.

    Science.gov (United States)

    Mortera-Blanco, Teresa; Dimitriou, Marios; Woll, Petter S; Karimi, Mohsen; Elvarsdottir, Edda; Conte, Simona; Tobiasson, Magnus; Jansson, Monika; Douagi, Iyadh; Moarii, Matahi; Saft, Leonie; Papaemmanuil, Elli; Jacobsen, Sten Eirik W; Hellström-Lindberg, Eva

    2017-08-17

    Mutations in the RNA splicing gene SF3B1 are found in >80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients and were also present in downstream myeloid and erythroid progenitor cells. While in agreement with previous studies, little or no evidence for clonal ( SF3B1 mutation) involvement could be found in mature B cells, consistent involvement at the pro-B-cell progenitor stage was established, providing definitive evidence for SF3B1 mutations targeting lymphomyeloid HSCs and compatible with mutated SF3B1 negatively affecting lymphoid development. Assessment of stem cell function in vitro as well as in vivo established that only HSCs and not investigated progenitor populations could propagate the SF3B1 mutated clone. Upon transplantation into immune-deficient mice, SF3B1 mutated MDS-RS HSCs differentiated into characteristic ring sideroblasts, the hallmark of MDS-RS. Our findings provide evidence of a multipotent lymphomyeloid HSC origin of SF3B1 mutations in MDS-RS patients and provide a novel in vivo platform for mechanistically and therapeutically exploring SF3B1 mutated MDS-RS. © 2017 by The American Society of Hematology.

  5. Evaluation of signalment, clinical, and laboratory variables as prognostic indicators in dogs with acute abdominal syndrome

    OpenAIRE

    SIMEONOVA, Galina; DINEV, Dinko; CHAPRAZOV, Tzvetan; ROYDEV, Rumen

    2013-01-01

    The aim of the study was to identify predictors of mortality and to propose a new severity scoring system in dogs with acute abdominal syndrome. A retrospective study was carried out on 58 dogs presented with acute abdominal syndrome with American Society of Anesthesiologists grades III-IV and treated surgically by exploratory laparotomy. Medical records were reviewed and information regarding dog signalment, history, clinical, and laboratory data; surgical findings; and outcome was collected...

  6. Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells.

    Science.gov (United States)

    Li, Jing; Yue, Lanzhu; Wang, Huaquan; Liu, Chunyan; Liu, Hui; Tao, Jinglian; Qi, Weiwei; Wang, Yihao; Zhang, Wei; Fu, Rong; Shao, Zonghong

    2016-01-01

    Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL-17). Our results suggested that Th17 cells might play an antitumor effect in the pathogenesis of MDS through IL-17/CTL pathway.

  7. EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development.

    Science.gov (United States)

    Okada, Morihiro; Shi, Yun-Bo

    2018-01-01

    The gene ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI encode zinc-finger proteins that have been recognized as important oncogenes in various types of cancer. In contrast to the established role of EVI and MDS/EVI in cancer development, their potential function during vertebrate postembryonic development, especially in organ-specific adult stem cells, is unclear. Amphibian metamorphosis is strikingly similar to postembryonic development around birth in mammals, with both processes taking place when plasma thyroid hormone (T3) levels are high. Using the T3-dependent metamorphosis in Xenopus tropicalis as a model, we show here that high levels of EVI and MDS/EVI are expressed in the intestine at the climax of metamorphosis and are induced by T3. By using the transcription activator-like effector nuclease gene editing technology, we have knocked out both EVI and MDS/EVI and have shown that EVI and MDS/EVI are not essential for embryogenesis and premetamorphosis in X. tropicalis On the other hand, knocking out EVI and MDS/EVI causes severe retardation in the growth and development of the tadpoles during metamorphosis and leads to tadpole lethality at the climax of metamorphosis. Furthermore, the homozygous-knockout animals have reduced adult intestinal epithelial stem cell proliferation at the end of metamorphosis (for the few that survive through metamorphosis) or during T3-induced metamorphosis. These findings reveal a novel role of EVI and/or MDS/EVI in regulating the formation and/or proliferation of adult intestinal adult stem cells during postembryonic development in vertebrates.-Okada, M., Shi, Y.-B. EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development. © FASEB.

  8. IDH mutations are closely associated with mutations of DNMT3A, ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution.

    Science.gov (United States)

    Lin, Chien-Chin; Hou, Hsin-An; Chou, Wen-Chien; Kuo, Yuan-Yeh; Liu, Chieh-Yu; Chen, Chien-Yuan; Lai, Yan-Jun; Tseng, Mei-Hsuan; Huang, Chi-Fei; Chiang, Ying-Chieh; Lee, Fen-Yu; Liu, Ming-Chih; Liu, Chia-Wen; Tang, Jih-Luh; Yao, Ming; Huang, Shang-Yi; Ko, Bor-Sheng; Wu, Shang-Ju; Tsay, Woei; Chen, Yao-Chang; Tien, Hwei-Fang

    2014-02-01

    Current information about clinical significance of IDH mutations in myelodysplastic syndromes (MDS), their association with other genetic alterations and the stability during disease progression is limited. In this study, IDH mutations were identified in 4.6% of 477 patients with MDS based on the FAB classification and in 2.2 % of 368 patients based on the 2008 WHO classification. IDH mutations were closely associated with older age, higher platelet counts, and mutations of DNMT3A (36.4% vs. 8.7%, P IDH2 mutation was a poor prognostic factor for overall survival in patients with lower-risk MDS, based on international prognosis scoring system (IPSS), FAB classification, WHO classification, or revised IPSS (all P ≦ 0.001), but not in higher-risk groups. Sequential studies in 151 patients demonstrated that all IDH-mutated patients retained the same mutation during disease evolution while none of the IDH-wild patients acquired a novel mutation during follow-ups. In conclusion, IDH mutation is a useful biomarker for risk stratification of patients with lower-risk MDS. IDH mutations are stable during the clinical course. The mutation, in association with other genetic alterations, may play a role in the development, but not progression of MDS. Copyright © 2013 Wiley Periodicals, Inc.

  9. Prognostic value of echocardiographic and Doppler parameters in horses admitted for colic complicated by systemic inflammatory response syndrome.

    Science.gov (United States)

    Borde, Laura; Amory, Hélène; Grulke, Sigrid; Leroux, Aurélia A; Houben, Rosa M; Detilleux, Johanne; Sandersen, Charlotte C

    2014-01-01

    To assess the prognostic value of echocardiographic parameters of left ventricular (LV) function in horses with systemic inflammatory response syndrome (SIRS). Prospective observational study. Veterinary teaching hospital. Forty-one horses admitted for colic with clinical evidence of SIRS. All horses underwent Doppler echocardiographic examination on admission. LV echocardiographic parameters, including pulsed-wave tissue Doppler imaging parameters, were compared between nonsurvivors (n = 29) and horses that survived to discharge (n = 12). With comparable heart rate and LV preload estimate, LV stroke volume index, the velocity time integral, deceleration time, ejection time of Doppler aortic flow, and peak early diastolic myocardial velocity were lower in the nonsurviving than in the surviving horses, while pre-ejection period to ejection time ratio (PEP/ET) of Doppler aortic flow and the peak early diastolic filling velocity to peak early diastolic myocardial velocity ratio (E/Em) were higher (P < 0.05). A cut-off value of 0.26 for PEP/ET predicted mortality with 100% sensitivity and 42% specificity (area under the receiver operating characteristic curve: 0.71), whereas a cut-off value of 2.67 for E/Em predicted mortality with 100% sensitivity and 83% specificity (area under the receiver operating characteristic curve: 0.89). Echocardiography may provide prognostic information in colic horses with clinical evidence of SIRS. Especially, PEP/ET and E/Em could be useful markers of systolic and diastolic dysfunction, respectively, to detect horses with a high risk of death requiring more intensive cardiovascular monitoring as it has been reported in human patients with septic shock. © Veterinary Emergency and Critical Care Society 2014.

  10. Determinants and Prognostic Impact of Heart Failure and Left Ventricular Ejection Fraction in Acute Coronary Syndrome Settings.

    Science.gov (United States)

    Agra Bermejo, Rosa; Cordero, Alberto; García-Acuña, José M; Gómez Otero, Inés; Varela Román, Alfonso; Martínez, Álvaro; Álvarez Rodríguez, Leyre; Abou-Jokh, Charigan; Rodríguez-Mañero, Moisés; Cid Álvarez, Belén; López-Palop, Ramón; Carrillo, Pilar; González-Juanatey, José R

    2017-12-15

    Contemporary data on the incidence and prognosis of heart failure (HF) and the influence of left ventricular ejection fraction (LVEF) in the setting of acute coronary syndrome (ACS) are scant. The aim of this study was to examine the relationship between LVEF and HF with long-term prognosis in a cohort of patients with ACS. This is a retrospective observational study of 6208 patients consecutively admitted for ACS to 2 different Spanish hospitals. Baseline characteristics were examined and a follow-up period was established for registration of death and HF rehospitalization as the primary endpoint. Among the study participants, 5064 had ACS without HF during hospitalization: 290 (5.8%) had LVEF<40%, 540 (10.6%) LVEF 40% to 49%, and 4234 (83.6%) LVEF ≥ 50%. The remaining 1144 patients developed HF in the acute phase: 395 (34.6%) had LVEF<40%, 251 (21.9%) LVEF 40% to 49%, and 498 (43.5%) LVEF ≥ 50%. Patients with LVEF 40% to 49% had a demographic and clinical profile with intermediate features between the LVEF <40% and LVEF ≥ 50% groups. Kaplan-Meier curves showed that mortality and HF readmissions were statistically different depending on LVEF in the non-HF group but not in the HF group. Left ventricular ejection fraction ≥ 50% was an independent prognostic factor in the non-HF group only. In ACS, long-term prognosis is considerably worse in patients who develop HF during hospitalization than in patients without HF, irrespective of LVEF. This parameter is a strong prognostic predictor only in patients without HF. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Prognostic value of glomerular collagen IV immunofluorescence studies in male patients with X-linked Alport syndrome.

    Science.gov (United States)

    Massella, Laura; Gangemi, Concetta; Giannakakis, Kostas; Crisafi, Antonella; Faraggiana, Tullio; Fallerini, Chiara; Renieri, Alessandra; Muda, Andrea Onetti; Emma, Francesco

    2013-05-01

    X-linked Alport syndrome (X-AS) is caused by mutations of the COL4A5 gene, which encodes for the collagen IV α5 chain (α5[COLIV]), resulting in structural and functional abnormalities of the glomerular basement membrane (GBM) and leading to CKD. The aim of the present study was to evaluate the prognostic value of residual collagen IV chain expression in the GBM of patients with X-AS. The medical records of 22 patients with X-AS from 21 unrelated families collected between 1987 and 2009 were reviewed (median age at last follow-up, 19.9 years; range, 5.4-35.1 years); GBM expression of α1, α3, and α5(COLIV) chains was assessed by immunofluorescence microscopy. GBM distribution of the α5(COLIV) chain was diffuse in 1 and segmental or absent in 21 of the 22 patients; the expression of the α3(COLIV) chain was diffuse in 5 of 22 patients and segmental or absent in 17 of 22 patients. Patients with diffuse staining for the α3(COLIV) chain presented with proteinuria significantly later (median age, 16.9 versus 6.1 years; P=0.02) and reached an estimated GFR < 90 ml/min per 1.73 m(2) at an older age (median age, 27.0 versus 14.9 years; P=0.01) compared with patients with segmental or absent staining. Two thirds of patients with abnormal α3(COLIV) expression by immunofluorescence studies had null or truncating COL4A5 mutations, as opposed to none of the 4 tested patients with diffuse α3(COLIV) chain glomerular distribution. These results indicate that maintained expression of the α3(COLIV) chain is an early positive prognostic marker in patients with X-linked Alport symdrome.

  12. The inter-rater reliability and prognostic value of coma scales in Nepali children with acute encephalitis syndrome.

    Science.gov (United States)

    Ray, Stephen; Rayamajhi, Ajit; Bonnett, Laura J; Solomon, Tom; Kneen, Rachel; Griffiths, Michael J

    2018-02-01

    Background Acute encephalitis syndrome (AES) is a common cause of coma in Nepali children. The Glasgow coma scale (GCS) is used to assess the level of coma in these patients and predict outcome. Alternative coma scales may have better inter-rater reliability and prognostic value in encephalitis in Nepali children, but this has not been studied. The Adelaide coma scale (ACS), Blantyre coma scale (BCS) and the Alert, Verbal, Pain, Unresponsive scale (AVPU) are alternatives to the GCS which can be used. Methods Children aged 1-14 years who presented to Kanti Children's Hospital, Kathmandu with AES between September 2010 and November 2011 were recruited. All four coma scales (GCS, ACS, BCS and AVPU) were applied on admission, 48 h later and on discharge. Inter-rater reliability (unweighted kappa) was measured for each. Correlation and agreement between total coma score and outcome (Liverpool outcome score) was measured by Spearman's rank and Bland-Altman plot. The prognostic value of coma scales alone and in combination with physiological variables was investigated in a subgroup (n = 22). A multivariable logistic regression model was fitted by backward stepwise. Results Fifty children were recruited. Inter-rater reliability using the variables scales was fair to moderate. However, the scales poorly predicted clinical outcome. Combining the scales with physiological parameters such as systolic blood pressure improved outcome prediction. Conclusion This is the first study to compare four coma scales in Nepali children with AES. The scales exhibited fair to moderate inter-rater reliability. However, the study is inadequately powered to answer the question on the relationship between coma scales and outcome. Further larger studies are required.

  13. [mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients].

    Science.gov (United States)

    Fei, Cheng-Ming; Gu, Shu-Cheng; Zhao, You-Shan; Guo, Juan; Li, Xiao; Chang, Chun-Kang

    2014-12-01

    This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P MDS patients (r = 0.502, P MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.

  14. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation

    NARCIS (Netherlands)

    Radivoyevitch, T.; Sachs, R. K.; Gale, R. P.; Molenaar, R. J.; Brenner, D. J.; Hill, B. T.; Kalaycio, M. E.; Carraway, H. E.; Mukherjee, S.; Sekeres, M. A.; Maciejewski, J. P.

    2016-01-01

    Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for

  15. Very Long-Term Prognostic Role of Admission BNP in Non-ST Segment Elevation Acute Coronary Syndrome

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    Fernando Bassan

    2016-01-01

    Full Text Available Abstract Background: BNP has been extensively evaluated to determine short- and intermediate-term prognosis in patients with acute coronary syndrome, but its role in long-term mortality is not known. Objective: To determine the very long-term prognostic role of B-type natriuretic peptide (BNP for all-cause mortality in patients with non-ST segment elevation acute coronary syndrome (NSTEACS. Methods: A cohort of 224 consecutive patients with NSTEACS, prospectively seen in the Emergency Department, had BNP measured on arrival to establish prognosis, and underwent a median 9.34-year follow-up for all-cause mortality. Results: Unstable angina was diagnosed in 52.2%, and non-ST segment elevation myocardial infarction, in 47.8%. Median admission BNP was 81.9 pg/mL (IQ range = 22.2; 225 and mortality rate was correlated with increasing BNP quartiles: 14.3; 16.1; 48.2; and 73.2% (p 72 years (OR = 3.79, 95% CI = 1.62-8.86, p = 0.002, BNP ≥ 100 pg/mL (OR = 6.24, 95% CI = 2.95-13.23, p < 0.001 and estimated glomerular filtration rate (OR = 0.98, 95% CI = 0.97-0.99, p = 0.049 were independent late-mortality predictors. Conclusions: BNP measured at hospital admission in patients with NSTEACS is a strong, independent predictor of very long-term all-cause mortality. This study allows raising the hypothesis that BNP should be measured in all patients with NSTEACS at the index event for long-term risk stratification.

  16. Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group

    Science.gov (United States)

    Braulke, Friederike; Platzbecker, Uwe; Müller-Thomas, Catharina; Götze, Katharina; Germing, Ulrich; Brümmendorf, Tim H.; Nolte, Florian; Hofmann, Wolf-Karsten; Giagounidis, Aristoteles A. N.; Lübbert, Michael; Greenberg, Peter L.; Bennett, John M.; Solé, Francesc; Mallo, Mar; Slovak, Marilyn L.; Ohyashiki, Kazuma; Le Beau, Michelle M.; Tüchler, Heinz; Pfeilstöcker, Michael; Nösslinger, Thomas; Hildebrandt, Barbara; Shirneshan, Katayoon; Aul, Carlo; Stauder, Reinhard; Sperr, Wolfgang R.; Valent, Peter; Fonatsch, Christa; Trümper, Lorenz; Haase, Detlef; Schanz, Julie

    2015-01-01

    International Prognostic Scoring Systems are used to determine the individual risk profile of myelodysplastic syndrome patients. For the assessment of International Prognostic Scoring Systems, an adequate chromosome banding analysis of the bone marrow is essential. Cytogenetic information is not available for a substantial number of patients (5%–20%) with dry marrow or an insufficient number of metaphase cells. For these patients, a valid risk classification is impossible. In the study presented here, the International Prognostic Scoring Systems were validated based on fluorescence in situ hybridization analyses using extended probe panels applied to cluster of differentiation 34 positive (CD34+) peripheral blood cells of 328 MDS patients of our prospective multicenter German diagnostic study and compared to chromosome banding results of 2902 previously published patients with myelodysplastic syndromes. For cytogenetic risk classification by fluorescence in situ hybridization analyses of CD34+ peripheral blood cells, the groups differed significantly for overall and leukemia-free survival by uni- and multivariate analyses without discrepancies between treated and untreated patients. Including cytogenetic data of fluorescence in situ hybridization analyses of peripheral CD34+ blood cells (instead of bone marrow banding analysis) into the complete International Prognostic Scoring System assessment, the prognostic risk groups separated significantly for overall and leukemia-free survival. Our data show that a reliable stratification to the risk groups of the International Prognostic Scoring Systems is possible from peripheral blood in patients with missing chromosome banding analysis by using a comprehensive probe panel (clinicaltrials.gov identifier:01355913). PMID:25344522

  17. Construction of new quantum MDS codes derived from constacyclic codes

    Science.gov (United States)

    Taneja, Divya; Gupta, Manish; Narula, Rajesh; Bhullar, Jaskaran

    Obtaining quantum maximum distance separable (MDS) codes from dual containing classical constacyclic codes using Hermitian construction have paved a path to undertake the challenges related to such constructions. Using the same technique, some new parameters of quantum MDS codes have been constructed here. One set of parameters obtained in this paper has achieved much larger distance than work done earlier. The remaining constructed parameters of quantum MDS codes have large minimum distance and were not explored yet.

  18. Decitabine of reduced dosage in Chinese patients with myelodysplastic syndrome: a retrospective analysis.

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    Xiao Li

    Full Text Available Decitabine has been approved for the treatment of all subtypes of myelodysplastic syndrome (MDS. However, the optimal regimen for decitabine treatment is not well established. In this study, an observational, retrospective and multi-center analysis was performed to explore the decitabine schedule for the treatment of MDS. A total of 79 patients received reduced dosage decitabine treatment (15 mg/M2/day intravenously for five consecutive days every four weeks. Fifty-three out of the 79 patients were defined as intermediate-2/high risk by international prognostic scoring system (IPSS risk category. 67.1% of MDS patients achieved treatment response including complete response (CR (n = 23, Partial response (n = 1, marrow CR (mCR with hematological improvement (HI (n = 11, mCR without HI (n = 11 and HI alone (n = 7 with a median of 4 courses (range 1-11. The median overall survival (OS was 18.0 months. The median OS was 22.0, 17.0 and 12.0 months in the patients with CR, those with other response, and those without response, respectively. In addition, this regimen contributed to zero therapy-related death and punctual course delivery, although III or IV grade of cytopenia was frequently observed. In conclusion, the 15 mg/M2/d×5 day decitabine regimen was effective and safe for Chinese MDS patients with IPSS score of 0.5 or higher.

  19. Focal Adhesion Kinase as a Potential Target in AML and MDS.

    Science.gov (United States)

    Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng; Yang, Hui; Garcia-Manero, Guillermo; Mak, Duncan H; Mu, Hong; Ruvolo, Vivian R; Qiu, Yihua; Coombes, Kevin; Zhang, Nianxiang; Ragon, Brittany; Weaver, David T; Pachter, Jonathan A; Kornblau, Steven; Andreeff, Michael

    2017-06-01

    Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics ( P = 2 × 10 -4 ) and relapse ( P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3 -ITD ( P = 0.0024) or RAS ( P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34 + ( P = 5.42 × 10 -20 ) and CD34 + CD38 - MDS ( P = 7.62 × 10 -9 ) cells compared with normal CD34 + cells. MDS patients with higher FAK in CD34 + cells tended to have better overall survival ( P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. Valuation of transfusion-free living in MDS: results of health utility interviews with patients

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    Lübbert Michael

    2009-09-01

    Full Text Available Abstract Background This study measured how myelodysplastic syndrome (MDS patients value transfusion independence (TI, reduced transfusions (RT and transfusion-dependence (TD using health utility assessment methodology. Methods 47 MDS patients were interviewed, US (n = 8, France (n = 9, Germany (n = 9 and the UK (n = 21, to elicit the utility value of TI, RT and TD. Health states were developed based on literature; patient forum discussions; and were validated by a hematologist. Face-to-face interviews used the feeling thermometer Visual Analogue Scale (VAS and the Time Trade-Off (TTO method to value the health states on a 0 (dead to 1 (perfect health scale. Socio-demographic, clinical, and quality-of-life (EQ-5D characteristics were surveyed to describe the patient sample. Results and Discussion The mean age was 67 years (range: 29-83; 45% male, 70% retired; 40% had secondary/high school education, or higher (32%, and 79% lived with family, a partner or spouse, or friends. The mean time from MDS diagnosis was 5 years (range:1-23. Most patients (87% received previous transfusions and 49% had received a transfusion in the last 3 months. Mean EQ-5D index score was 0.78; patients reported at least some problem with mobility (45%, usual activities (40%, pain/discomfort (47%, and anxiety/depression (34%. Few patients had difficulty understanding the VAS (n = 3 and TTO (n = 4 exercises. Utility scores for TI were higher than for RT (0.84 vs. 0.77; p Conclusion Patients value TI, suggesting an important role for new treatments aiming to achieve greater TI in MDS. These results can be used in preference-based health economic evaluation of new MDS treatments, such as in future cost-utility studies.

  1. SPECT in the Kleine-Levin syndrome, a possible diagnostic and prognostic aid?

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    Patrick Emanuel Vigren

    2014-09-01

    Full Text Available INTRODUCTION: Kleine-Levin syndrome (KLS is a rare syndrome of periodic hypersomnia and behavioral and cognitive symptoms based on clinical criteria. In the setting of differential diagnosis of hypersomnia disorders, an objective diagnostic aid is desirable. A promising modality is single photon emission computed tomography (SPECT. As intraepisodal investigations are difficult to perform, an interepisodal investigation would be very helpful. Another aim of the study was to correlate SPECT findings to prognosis. METHODS AND MATERIAL: 24 KLS-patients were categorized as severe or non-severe based on clinical characteristics. The clinical characteristics were analyzed in relation to SPECT-examinations performed between hypersomnia periods (interepisodal or after remission, as a clinical routine investigation.RESULTS: 48% of the KLS-patients have hypoperfusion in the temporal or fronto-temporal regions. In patients that have undergone remission, 56% show that pattern. There were no specific findings related to prognosis.DISCUSSION/CONCLUSION: SPECT might be a diagnostic aid, in a setting of hypersomnia experience. With a sensitivity of 48%, interepisodal SPECT alone cannot be used for diagnosing KLS.

  2. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

    Science.gov (United States)

    Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

    2015-01-01

    Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

  3. Are the MDS-UPDRS-based composite scores clinically applicable?

    Science.gov (United States)

    Makkos, Attila; Kovács, Márton; Aschermann, Zsuzsanna; Harmat, Márk; Janszky, József; Karádi, Kázmér; Kovács, Norbert

    2018-02-28

    The International Parkinson and Movement Disorder Society-sponsored UPDRS (MDS-UPDRS) is a powerful clinical outcome measure. To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  4. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome.

    Science.gov (United States)

    Gao, Hong; Ruan, Jianqing Q; Chen, Jie; Li, Na; Ke, Changqiang Q; Ye, Yang; Lin, Ge; Wang, Jiyao Y

    2015-01-01

    The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs) as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS. Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients' age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis. Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23 patients with pyrrolizidine alkaloid-associated HSOS, ten recovered, four developed chronic disease, eight died, and one underwent liver transplantation within 6 months after onset. Blood PPAs were detectable in 24 of 40 patients with concentrations from 0.05 to 74.4 nM. Sensitivity and specificity of the test for diagnosis of pyrrolizidine alkaloid-associated HSOS were 100% (23/23) and 94.1% (23/24), respectively. The positive predictive value was 95.8% and the negative predictive value was 100%, whereas the positive likelihood ratio was 23.81. The level of blood PPAs in the severe group (died or received liver transplantation) was significantly higher than that in the recovery/chronicity group (P=0.004). Blood PPAs measured by ultra-performance liquid

  5. Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study.

    Science.gov (United States)

    Stauder, Reinhard; Yu, Ge; Koinig, Karin A; Bagguley, Tim; Fenaux, Pierre; Symeonidis, Argiris; Sanz, Guillermo; Cermak, Jaroslav; Mittelman, Moshe; Hellström-Lindberg, Eva; Langemeijer, Saskia; Holm, Mette Skov; Mądry, Krzysztof; Malcovati, Luca; Tatic, Aurelia; Germing, Ulrich; Savic, Aleksandar; van Marrewijk, Corine; Guerci-Bresler, Agnès; Luño, Elisa; Droste, Jackie; Efficace, Fabio; Smith, Alex; Bowen, David; de Witte, Theo

    2018-03-06

    In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Impairments were compared with age- and sex-matched EuroQol Group norms. A significant proportion of MDS patients reported moderate/severe problems in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort, and EQ-VAS were significantly more frequent in the old, in females, and in those with high co-morbidity burden, low haemoglobin levels, or red blood cells transfusion need (p MDS patients (p MDS-related restrictions in the dimension mobility were most prominent in males, and in older people (p MDS experience a pronounced reduction in HRQoL and a clustering of restrictions in distinct dimensions of HRQoL as compared with reference populations.

  6. Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS.

    Science.gov (United States)

    Sohn, Sang Kyun; Moon, Joon Ho

    2015-08-01

    According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Prevalence and prognostic relevance of atrial fibrillation in patients with Takotsubo syndrome

    DEFF Research Database (Denmark)

    Stiermaier, Thomas; Santoro, Francesco; Eitel, Charlotte

    2017-01-01

    was evaluated in median 2.9years after the acute event. RESULTS: Atrial fibrillation was found in 97 TTS patients (25.1%) and was associated with older age (pventricular ejection fraction (p... fibrillation (35.2% versus 15.3%; hazard ratio 3.02, 95% confidence interval 1.90-4.78; pfibrillation was identified as an independent determinant of outcome even after adjustment for clinical variables, left ventricular functional parameters (ballooning......BACKGROUND: Takotsubo syndrome (TTS) is associated with a considerable risk of complications during the acute phase and substantial long-term mortality rates. Concomitant atrial fibrillation may have an impact on outcome in these patients. Aim of this study was to assess the prevalence...

  8. Prognostic Utility of Clinical Epilepsy Severity Score Versus Pretreatment Hypsarrhythmia Scoring in Children With West Syndrome.

    Science.gov (United States)

    Sehgal, Rachna; Gulati, Sheffali; Sapra, Savita; Tripathi, Manjari; Pandey, Ravinder Mohan; Kabra, Madhulika

    2017-07-01

    This cross-sectional study assessed the impact of clinical epilepsy severity and pretreatment hypsarrhythmia severity on epilepsy and cognitive outcomes in treated children with West syndrome. Thirty-three children, aged 1 to 5 years, with infantile spasms were enrolled if pretreatment EEG records were available, after completion of ≥1 year of onset of spasms. Neurodevelopment was assessed by Development Profile 3 and Gross Motor Function Classification System. Epilepsy severity in the past 1 year was determined by the Early Childhood Epilepsy Severity Score (E-Chess). Kramer Global Score of hypsarrhythmia severity was computed. Kramer Global Score (≤8) and E-Chess (≤9) in the past 1 year were associated with favorable epilepsy outcome but not neurodevelopmental or motor outcome.

  9. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS

    Science.gov (United States)

    Schneider, Rebekka K.; Ademà, Vera; Heckl, Dirk; Järås, Marcus; Mallo, Mar; Lord, Allegra M.; Chu, Lisa P.; McConkey, Marie E.; Kramann, Rafael; Mullally, Ann; Bejar, Rafael; Solé, Francesc; Ebert, Benjamin L.

    2014-01-01

    Summary The Casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the non-deleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target. PMID:25242043

  10. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome

    Directory of Open Access Journals (Sweden)

    Gao H

    2015-08-01

    Full Text Available Hong Gao,1,* Jianqing Q Ruan,2,* Jie Chen,1 Na Li,2 Changqiang Q Ke,3 Yang Ye,3–5 Ge Lin,2,4,5 Jiyao Y Wang1,61Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong; 3Shanghai Institute of Materia Medica, Shanghai, People’s Republic of China; 4Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines, Shanghai Institute of Materia Medica, 5Chinese University of Hong Kong, Hong Kong; 6Center of Evidence-Based Medicine Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this work and share first authorship Background: The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS.Methods: Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients’ age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis.Results: Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23

  11. TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients

    Science.gov (United States)

    Caceres, Gisela; McGraw, Kathy; Yip, Bon Ham; Pellagatti, Andrea; Johnson, Joseph; Zhang, Ling; Liu, Kenian; Zhang, Lan Min; Fulp, William J.; Lee, Ji-Hyun; Al Ali, Najla H.; Basiorka, Ashley; Smith, Larry J.; Daugherty, F. Joseph; Littleton, Neil; Wells, Richard A.; Sokol, Lubomir; Wei, Sheng; Komrokji, Rami S.; Boultwood, Jacqueline; List, Alan F.

    2013-01-01

    Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = −0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS. PMID:24043769

  12. Diffusion Magnetic Resonance Imaging May Provide Prognostic Information in Osmotic Demyelination Syndrome: Report of a Case

    Energy Technology Data Exchange (ETDEWEB)

    Dervisoglu, E.; Yegenaga, I.; Anik, Y.; Sengul, E.; Turgut, T. [Kocaeli Univ. (Turkey). Internal Medicine

    2006-03-15

    Hyponatremia and its rapid correction may cause osmotic demyelination syndrome (ODS) with damage to the pontine and extrapontine areas of the brain. The damage may become persistent or may regress and disappear during follow-up. We describe the case of a 35-year-old woman with chronic renal failure who was admitted to the emergency department with profound hyponatremia which was corrected rapidly after hemodialysis treatment. During follow-up, she developed quadriparesis and dysartria. Magnetic resonance imaging (MRI) demonstrated abnormalities characteristic of ODS in the pons as well as the basal ganglia with increased signal intensity on T2 and diffusion-weighted (DW) MRI and low apparent diffusion coefficient (ADC) values. After the sixth day, her clinical status improved progressively. Control MRI revealed rapid normalization of the ADC values during the first week and month parallel to the clinical improvement. However, the hyperintensities on T2-weighted images persisted. Four months later the MRI findings were completely normal. The close relationship between the ADC abnormality and the clinical status suggests that DW-MRI may be useful in predicting the prognosis of ODS. Keywords: Apparent diffusion coefficient; correction of hyponatremia; magnetic resonance imaging; osmotic demyelination.

  13. Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance.

    Science.gov (United States)

    Sorino, Claudio; Scichilone, Nicola; D'Amato, Maria; Patella, Vincenzo; DI Marco, Fabiano

    2017-06-01

    The term asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has been proposed for individuals with features of both asthma and COPD. Several attempts have been done to define ACOS on the basis of medical history, symptoms, and functional findings. The main diagnostic criteria include airflow obstruction with a strong although incomplete reversibility to bronchodilation tests, a significant exposure to cigarette or biomass smoke, and a history of atopy or asthma. Additional diagnostic elements include eosinophilic airway and systemic inflammation, a good response to corticosteroid treatment, and a high concentration of exhaled nitric oxide. ACOS should be distinguished from asthma with not fully reversible bronchial obstruction due to airway remodeling, thus the lack of smoking exposure should exclude the diagnosis of ACOS. In patients without a documented history of asthma before 40 years of age, an increase in FEV1 after bronchodilator >400 mL should be required to diagnose ACOS. ACOS has been found to be associated with impaired physical performance, functional ability, and health-related quality of life. The prevalence of ACOS increases with aging, then it is relatively stable in elderly individuals (>65 years). Long-term mortality of subjects with ACOS is similar to COPD, and worse than asthma and healthy controls. Future research is still needed to improve the understanding and management of ACOS.

  14. Hypoplastic left heart syndrome and the nutmeg lung pattern in utero: a cause and effect relationship or prognostic indicator?

    Energy Technology Data Exchange (ETDEWEB)

    Saul, David; Johnson, Ann M.; Victoria, Teresa [The Children' s Hospital of Philadelphia, Radiology Department, Philadelphia, PA (United States); Degenhardt, Karl; Rychik, Jack [The Children' s Hospital of Philadelphia, Cardiac Center and Fetal Heart Program, Philadelphia, PA (United States); Iyoob, Suzanne D.; Johnson, Mark P. [The Children' s Hospital of Philadelphia, Center for Fetal Diagnosis and Treatment, Philadelphia, PA (United States); Surrey, Lea F. [The Children' s Hospital of Philadelphia, Pathology Department, Philadelphia, PA (United States)

    2016-04-15

    Hypoplastic left heart syndrome (HLHS) is the third most common cause of critical congenital heart disease in newborns, and one of the most challenging forms to treat. Secondary pulmonary lymphangiectasia has been recognized in association with HLHS, an appearance described on fetal MRI as the ''nutmeg lung.'' To investigate the association of fetal nutmeg lung with HLHS survival. A retrospective search of the fetal MRI database was performed. The nutmeg lung pattern was defined as T2 heterogeneous signal with tubular structures radiating peripherally from the hila. Postnatal echocardiograms and charts were reviewed. Forty-four fetal MR studies met inclusion criteria, of which 4 patients (9%) had the nutmeg lung pattern and 3 of whom also had restrictive lesions. Mortality in this nutmeg lung group was 100% by 5 months of age. Of the 40 patients without nutmeg lung, mortality/orthotopic heart transplant (OHT) was 35%. Of these 40 patients without nutmeg lung, 5 had restriction on echo, 3 of whom died/had OHT before 5 months of age (60% of patients with restriction and non-nutmeg lung). There was a significantly higher incidence of restrictive lesions (P = 0.02) and mortality/OHT (P = 0.02) in patients with nutmeg lung compared to those without. The nutmeg lung MR appearance in HLHS fetuses is associated with increased mortality/OHT (100% in the first 5 months of life compared to 35% with HLHS alone). Not all patients with restrictive lesions develop nutmeg lung, and outcome is not as poor when restriction is present in isolation. Dedicated evaluation for nutmeg lung pattern on fetal MR studies may be useful to guide prognostication and aid clinicians in counseling parents of fetuses with HLHS. (orig.)

  15. KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Tanigawa Koichi

    2011-03-01

    Full Text Available Abstract Background KL-6 is a mucin-like glycoprotein expressed on the surface of alveolar type II cells. Elevated concentrations of KL-6 in serum and epithelial lining fluid (ELF in patients with acute respiratory distress syndrome (ARDS have been previously reported; however, kinetics and prognostic significance of KL-6 have not been extensively studied. This study was conducted to clarify these points in ARDS patients. Methods Thirty-two patients with ARDS who received mechanical ventilation under intubation were studied for 28 days. ELF and blood were obtained from each patient at multiple time points after the diagnosis of ARDS. ELF was collected using a bronchoscopic microsampling procedure, and ELF and serum KL-6 concentrations were measured. Results KL-6 levels in ELF on days 0 to 3 after ARDS diagnosis were significantly higher in nonsurvivors than in survivors, and thereafter, there was no difference in concentrations between the two groups. Serum KL-6 levels did not show statistically significant differences between nonsurvivors and survivors at any time point. When the highest KL-6 levels in ELF and serum sample from each patient were examined, KL-6 levels in both ELF and serum were significantly higher in nonsurvivors than in survivors. The optimal cut-off values were set at 3453 U/mL for ELF and 530 U/mL for serum by receiver operating characteristic (ROC curve analyses. Patients with KL-6 concentrations in ELF higher than 3453 U/mL or serum concentrations higher than 530 U/mL had significantly lower survival rates up to 90 days after ARDS diagnosis. Conclusions ELF and serum KL-6 concentrations were found to be good indicators of clinical outcome in ARDS patients. Particularly, KL-6 levels in ELF measured during the early period after the diagnosis were useful for predicting prognosis in ARDS patients.

  16. [Study of prognostic factors and prevalence of post-thrombotic syndrome in patients with deep vein thrombosis in Spain].

    Science.gov (United States)

    Ordi, Josep; Salmerón, Luis; Acosta, Fernando; Camacho, Isabel; Marín, Núria

    2016-01-15

    The prevalence of post-thrombotic syndrome (PTS) in Spain is not known accurately at present. The main objective of this study was to determine the prevalence of PTS and the possible prognostic factors related to its development and impact on quality of life. This was an observational, multicenter, cross-sectional and retrospective study of patients who had suffered a deep vein thrombosis (DVT) between March 2010 and March 2011. The Villalta scale was applied as a standardized assessment of PTS at the enrollment visit. According to the score, distribution was: patients with PTS (score>4) and patients without PTS (score ≤4). Subsequently, DVT data and risk factors were collected retrospectively. The quality of life of patients was evaluated. In total 511 patients with DVT were enrolled, of which 7 patients were excluded as they did not meet the inclusion/exclusion criteria. The prevalence of PTS was 53%, with 56.2% having a mild character, 20.6% moderate, and 23.2% severe. The presence of risk factors for DVT including immobilization, hormonal therapy and obesity was significantly higher in patients with PTS than in patients without PTS. There were not significant differences in the location of the DVT. The perception of patients about their health was significantly worse in patients with DVT. The prevalence of PTS in patients with DVT is very high. The presence of risk factors for DVT clearly contributes to a greater predisposition to suffering PTS in an average time of 2 years. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  17. Hypoplastic left heart syndrome and the nutmeg lung pattern in utero: a cause and effect relationship or prognostic indicator?

    International Nuclear Information System (INIS)

    Saul, David; Johnson, Ann M.; Victoria, Teresa; Degenhardt, Karl; Rychik, Jack; Iyoob, Suzanne D.; Johnson, Mark P.; Surrey, Lea F.

    2016-01-01

    Hypoplastic left heart syndrome (HLHS) is the third most common cause of critical congenital heart disease in newborns, and one of the most challenging forms to treat. Secondary pulmonary lymphangiectasia has been recognized in association with HLHS, an appearance described on fetal MRI as the ''nutmeg lung.'' To investigate the association of fetal nutmeg lung with HLHS survival. A retrospective search of the fetal MRI database was performed. The nutmeg lung pattern was defined as T2 heterogeneous signal with tubular structures radiating peripherally from the hila. Postnatal echocardiograms and charts were reviewed. Forty-four fetal MR studies met inclusion criteria, of which 4 patients (9%) had the nutmeg lung pattern and 3 of whom also had restrictive lesions. Mortality in this nutmeg lung group was 100% by 5 months of age. Of the 40 patients without nutmeg lung, mortality/orthotopic heart transplant (OHT) was 35%. Of these 40 patients without nutmeg lung, 5 had restriction on echo, 3 of whom died/had OHT before 5 months of age (60% of patients with restriction and non-nutmeg lung). There was a significantly higher incidence of restrictive lesions (P = 0.02) and mortality/OHT (P = 0.02) in patients with nutmeg lung compared to those without. The nutmeg lung MR appearance in HLHS fetuses is associated with increased mortality/OHT (100% in the first 5 months of life compared to 35% with HLHS alone). Not all patients with restrictive lesions develop nutmeg lung, and outcome is not as poor when restriction is present in isolation. Dedicated evaluation for nutmeg lung pattern on fetal MR studies may be useful to guide prognostication and aid clinicians in counseling parents of fetuses with HLHS. (orig.)

  18. Muscular atrophy in severe cases of cubital tunnel syndrome: prognostic factors and outcome after surgical treatment.

    Science.gov (United States)

    Bruder, Markus; Dützmann, Stephan; Rekkab, Nourdin; Quick, Johanna; Seifert, Volker; Marquardt, Gerhard

    2017-03-01

    Cubital tunnel syndrome (CuTS) is a frequent neuropathy, leading to sensor-motoric dysfunction. Many patients even present with muscular atrophy as a sign for severe and long-lasting nerve impairment, usually suggesting unfavourable outcome. We analysed if those patients benefit from surgical treatment on a long-term basis. Between January 2010 and March 2015, 42 consecutive cases of CuTS with atrophy of the intrinsic hand muscles were surgically treated in our department. Clinical data of the treatment course and postoperative results were collected. Follow-up was prospectively assessed according to McGowen grading and Bishop outcome score. Mean follow-up time was 39.8 (±17.0) months. All patients were treated with in situ decompression; in 33%, submuscular transposition was performed. Forty-five percent showed improvement of sensory deficits and 57% showed improvement of motor deficits 6 months after the operation. Atrophy improved in 76%. At the time of follow-up, 79% were satisfied with the postoperative result and 77% of patients reached good or excellent outcome according to modified Bishop rating scale. Patients with improvement of atrophy had significantly shorter symptom duration period (7 ± 10 months vs 26 ± 33 months; p atrophy improvement was less likely (p atrophy of the intrinsic hand muscles, surgical treatment enables improvement of sensory function, motor function and atrophy even in cases with muscular atrophy. Atrophy improvement was more likely in cases of short symptom duration and less likely in cases with pseudoneuroma.

  19. Prognostic Accuracy of the GRACE Score in Octogenarians and Nonagenarians with Acute Coronary Syndromes

    Directory of Open Access Journals (Sweden)

    Antonio Mauricio dos Santos Cerqueira Junior

    2018-02-01

    Full Text Available Abstract Background: The GRACE Score was derived and validated from a cohort in which octogenarians and nonagenarians were poorly represented. Objective: To test the accuracy of the GRACE score in predicting in-hospital mortality of very elderly individuals with acute coronary syndromes (ACS. Methods: Prospective observational study conducted in the intensive coronary care unit of a tertiary center from September 2011 to August 2016. Patients consecutively admitted due to ACS were selected, and the very elderly group was defined by age ≥ 80 years. The GRACE Score was based on admission data and its accuracy was tested regarding prediction of in-hospital death. Statistical significance was defined by p value < 0,05. Results: A total of 994 individuals was studied, 57% male, 77% with non-ST elevation myocardial infarction and 173 (17% very elderly patients. The mean age of the sample was 65 ± 13 years, and the mean age of very elderly patients subgroup was 85 ± 3.7 years. The C-statistics of the GRACE Score in very elderly patients was 0.86 (95% CI = 0.78 - 0.93, with no difference when compared to the value for younger individuals 0.83 (95% CI = 0.75 - 0.91, with p = 0.69. The calibration of the score in very elderly patients was described by χ2 test of Hosmer-Lemeshow = 2.2 (p = 0.98, while the remaining patients presented χ2 = 9.0 (p = 0.35. Logistic regression analysis for death prediction did not show interaction between GRACE Score and variable of very elderly patients (p = 0.25. Conclusion: The GRACE Score in very elderly patients is accurate in predicting in-hospital ACS mortality, similarly to younger patients.

  20. Complications in mechanically ventilated patients of Guillain–Barre syndrome and their prognostic value

    Directory of Open Access Journals (Sweden)

    Archana Becket Netto

    2017-01-01

    Full Text Available Introduction: The spectrum of various complications in critically ill Guillain–Barre syndrome (GBS and its effect on the prognosis is lacking in literature. This study aimed at enumerating the complications in such a cohort and their significance in the prognosis and mortality. Materials and Methods: Retrospective case record analysis of all consecutive mechanically ventilated patients of GBS in neurology Intensive Care Unit (ICU of a tertiary care institute for 10 years was done. Demographic, laboratory, and treatment details and outcome parameters were recorded. Results: Among the 173 patients were 118 men and 55 women (2.1:1, aged 1–84 years. The average number of ICU complications per patient was 6.8 ± 1.8 (median = 7, range = 1–12. The most common complication was tracheobronchitis (128. Other pulmonary complications were found in 36 patients. The next was metabolic hyponatremia (115 hypokalemia (67, hypocalcemia (13, stress hyperglycemia (10, hyperkalemia (8, hypernatremia (9. Sepsis (40, UTI (47, dysautonomia (27, hypoalbuminemia (76, anemia (75, seizures (8, paralytic ileus (5, bleeding (4, anoxic encephalopathy (3, organ failures (12, deep vein thrombosis (7, and drug rashes (1 were also noted. The complications, considered significant in causing death, Hughes scale ≤ 3 at discharge, prolonged mechanical ventilation (>21 days and hospitalization (>36 days were pneumonia, hyponatremia, hypokalemia, urinary infection, tracheobronchial infections, hypoalbuminemia, sepsis, anemia dysautonomia. Conclusion: Active monitoring and appropriate and early intervention by the clinician will improve the quality of life of these patients and reduce the cost of prolonged mechanical ventilation and ICU stay.

  1. Hereditary Predispositions to Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah A. Bannon

    2016-05-01

    Full Text Available Myelodysplastic syndromes (MDS are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA, dyskeratosis congenita (DC, Diamond–Blackfan anemia (DBA, and Shwachman–Diamond syndrome (SBS, hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA and significantly increased risks for MDS and/or acute myeloid leukemia (AML in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.

  2. An Exercise in Extrapolation: Clinical Management of Atypical CML, MDS/MPN-Unclassifiable, and MDS/MPN-RS-T.

    Science.gov (United States)

    Talati, Chetasi; Padron, Eric

    2016-12-01

    According to the recently published 2016 World Health Organization (WHO) classification of myeloid malignancies, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and MDS/MPN ring sideroblasts with thrombocytosis (MDS/MPN-RS-T). MDS/MPN-RS-T was previously a provisional category known as refractory anemia with ring sideroblasts with thrombocytosis (RARS-T) which has now attained a distinct designation in the 2016 WHO classification. In this review, we focus on biology and management of aCML, MDS/MPN-U, and MDS/MPN-RS-T. There is considerable overlap between these entities which we attempt to further elucidate in this review. We also discuss recent advances in the field of molecular landscape that further defines and characterizes this heterogeneous group of disorders. The paucity of clinical trials available secondary to unclear pathogenesis and rarity of these diseases makes the management of these entities clinically challenging. This review summarizes some of the current knowledge of the molecular pathogenesis and suggested treatment guidelines based on the available data.

  3. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS

    DEFF Research Database (Denmark)

    Holm, Mette; Dybedahl, I; Holm, Mette

    2014-01-01

    This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a trans......This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks...... after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS...... patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations....

  4. [Myelodisplasic syndromes diagnosed in a geriatric hospital: morphological profile in 100 patients].

    Science.gov (United States)

    Dewulf, G; Gouin, I; Pautas, E; Gaussem, P; Chaïbi, P; Andreux, J-P; Siguret, V

    2004-01-01

    Myelodysplastic syndrome (MDS) is particularly common in geriatric practice. As few data are available in very elderly patients, we conducted a 54-month retrospective study in patients over 70 years with MDS diagnosed at Hôpital Charles Foix. Patients with cobalamine, folate or iron deficiency were excluded. Regarding biological and morphologic approaches, MDS patients were classified according to the FAB criteria. We then tempted to reclassify the patients according to the WHO criteria. The Bournemouth scoring system was used as a prognostic tool. During the study period, 100 patients were included, 29 males and 71 females, median age 86 +/- 7 years (70-103). At the time of bone marrow sampling, a peripheral blood cytopenia was documented in 64 patients, a bicytopenia in 27 patients and a pancytopenia in 9 patients. Isolated anaemia (Hb 100 fL) was observed in 21 % of the cases. According to the FAB criteria, the 100 patients were classified as follows: refractory anaemia (RA): 79%; RA with ringed sideroblasts (RARS): 8%; RA with excess of blasts (RAEB): 8%; RAEB in transformation: 1%; chronic myelomonocytic leukaemia: 4%. According to the WHO classification, the patients were reclassified as follows: RA (unilineage) (with or without ringed sideroblasts): 10%; refractory cytopenia with multilineage dysplasia with or without ringed sideroblasts (RCMD): 73%; RAEB: 7% (RAEB-1 6%, RAEB-21%); MDS/Myeloproliferative disorder: 4%; unclassified (hypocellularity): 5%; acute leukaemia: 1%. In order to estimate prognosis at the time of the bone marrow aspirate, we calculated the Bournemouth'score: 8 patients scored 0,57 scored 1,25 scored 2,8 scored 3 and 2 scored 4. In this geriatric population, 83% cases of MDS are RA or RCMD (with or without sideroblasts); MDS with excess of blasts are uncommon. Thus, elderly patients under study with MDS were diagnosed at an earlier stage of the disease than younger ones from series published in the literature. Due to frequent

  5. Azacitidine: a review of its use in the management of myelodysplastic syndromes/acute myeloid leukaemia.

    Science.gov (United States)

    Keating, Gillian M

    2012-05-28

    Azacitidine (Vidaza®) is a pyrimidine nucleoside analogue of cytidine. This article reviews the clinical efficacy and tolerability of azacitidine in the treatment of patients with myelodysplastic syndromes (MDS)/acute myeloid leukaemia (AML), as well as summarizing its pharmacological properties. The randomized, multicentre Cancer and Leukemia Group B 9221 trial compared the efficacy of subcutaneous azacitidine with that of supportive care alone in patients with MDS fulfilling French-American-British (FAB) classification criteria. The overall response rate, the complete response rate and the complete plus partial response rate were significantly higher in patients receiving azacitidine than in those receiving supportive care alone. The randomized, open-label, multicentre AZA-001 trial compared the efficacy of subcutaneous azacitidine with that of conventional care in adults with higher-risk (i.e. International Prognostic Scoring System intermediate-2-risk or high-risk classification) MDS/AML. Prior to randomization, investigators preselected patients to the conventional care strategy considered most appropriate (i.e. best supportive care, low-dose cytarabine or intensive chemotherapy). The median duration of overall survival was significantly prolonged by 9.4 months in patients with higher-risk MDS receiving azacitidine versus those receiving conventional care. The survival benefit seen with azacitidine versus conventional care was maintained across various patient subgroups (e.g. in patients aged ≥75 years, in those who did not achieve complete remission and in patients with WHO-defined AML). The efficacy of subcutaneous or intravenous azacitidine was also shown in a noncomparative trial in Japanese patients with MDS fulfilling FAB classification criteria, and registry programmes in various countries support the efficacy of azacitidine in patients with MDS. Azacitidine was generally well tolerated in patients with MDS, including in the elderly. Across trials

  6. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E

    2013-01-01

    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  7. HEMATOPOIETIC CELL TRANSPLANTATION FOR OLDER PATIENTS WITH MDS

    Directory of Open Access Journals (Sweden)

    Mazyar Shadman

    2014-09-01

    Full Text Available The incidence of myeloid malignancies, including myelodysplastic syndromes (MDS increases with age. While several therapeutic modalities have been developed, for most of these patients the only treatment with curative potential is allogeneic hematopoietic cell transplantation (HCT. The development of reduced/low intensity transplant conditioning regimens allows to successfully transplant patients in their ‘60s and even ‘70s, although comorbidities may determine who does come to transplantation and who does not. Also, as many as half of the patients will develop graft versus host disease (GVHD, even with HLA matched  donors, requiring therapy for extended periods of time,  and GVHD and treatment  with glucocorticoids is likely to impact the quality  of life. Nevertheless, dependent upon disease stage at HCT, the presence of comorbidities and the regimen used, 30% to 50% of patients  60 years of age or older, may survive long-term cured of their disease. Future studies should focus on the incorporation of non-transplant modalities into the overall transplant approach, the prevention of GVHD, and the utilization of immunotherapy to reduce the incidence of relapse and GVHD and further improve overall transplant success.

  8. PP2A: The Achilles Heal in MDS with 5q Deletion

    Directory of Open Access Journals (Sweden)

    David eSallman

    2014-09-01

    Full Text Available Myelodysplastic syndromes (MDS represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q (del(5q is pathologically and clinically distinct. Patients with del(5q MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14 gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Since its approval in 2005, lenalidomide has changed the natural course of the disease. Patients who achieve transfusion independence and/or a cytogenetic response with lenalidomide have a decreased risk of progression to AML and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of lenalidomide in del(5q MDS has advanced therapeutic strategies for this disease. The selective cytotoxicity of lenalidomide in del(5q clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Acα. PP2A is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Acα results in cell cycle arrest and apoptosis in del(5q cells. Targeted knockdown of PP2Acα using siRNA is sufficient to sensitize non-del(5q clones to lenalidomide. Through its inhibitory effect on PP2A, lenalidomide stabilizes MDM2 to restore p53 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of patients with del(5q MDS develop resistance to lenalidomide over time associated with PP2Acα overexpression. Targeted inhibition of PP2A with a more potent inhibitor has emerged as an attractive therapeutic approach for patients with del(5q MDS.

  9. Asthma and risk of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Frederiksen, Henrik; Farkas, Dóra Körmendiné; Horváth-Puhó, Erzsébet

    2017-01-01

    BACKGROUND: Risk factors for the development of myelodysplastic syndromes (MDS) include age, exposure to ionising radiation, and cytotoxic drug treatment. Recently, asthma also has been suggested as a risk factor for MDS. METHODS: We undertook this nationwide population-based cohort study...... on patients with a first-time hospital-based asthma diagnosis during 2002-2013 and followed them for the development of MDS/chronic myelomonocytic leukaemia (CMML). RESULTS: We identified 75 995 patients with incident asthma and no previous MDS/CMML diagnosis. Seventy-eight patients subsequently developed MDS...... and nine patients developed CMML during 402 892 person-years. The cumulative risks of developing MDS/CMML among asthma patients were 0.02% (95% CI: 0.01-0.04%) and 0.07% (95% CI: 0.05-0.09%) during the first year and the first five years of follow-up, respectively. The standardised incidence ratio of MDS...

  10. Progress in the diagnosis of and therapy for MDS.

    Science.gov (United States)

    Nannya, Yasuhito

    2016-01-01

    The WHO classification system of MDS 4 th edition was recently updated. This revision includes nomenclature changes, reflecting the policy of the revision team to emphasize morphological features over cytopenias. Other changes are 1) taking SF3B1 mutation status into account for the definition criteria of MDS-RS (ring sideroblasts), 2) allowing for one additional cytogenetic abnormality (excluding -7/del (7q)) to be diagnosed as 'MDS with isolated del (5q)', 3) sub-classifying MDS-U according to the reasons for being included in this category, and 4) changing the diagnostic rules for myeloid neoplasms with erythroid blast predominance. This session also deals with recent topics in hematopoietic stem cell transplantation (HSCT) as an example of progress in therapy for MDS. Although HSCT is the only curative therapy for MDS, high treatment related mortality precludes its applicability especially for elderly patients, for whom demethylating agents are an alternative. Recently, reports on both well-designed retrospective or prospective studies have validated the advantage of HSCT over demethylating agents for patients of comparatively advanced age with higher risk MDS. Optimal intensity of conditioning regimens for HSCT is another controversial topic for which preliminary results of randomized controlled trials have been released and will be introduced in this session.

  11. Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India.

    Science.gov (United States)

    Vyas, Chintan; Jain, Sandeep; Kapoor, Gauri

    2018-01-01

    Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P  = 0.26] with 6390 patient years of follow up. Primary malignancy included sarcoma [bone (2), soft tissue (2)], B-non-Hodgkin lymphoma (2) and acute lymphoblastic leukemia (2). The median cumulative equivalent doses of cyclophosphamide, doxorubicin and etoposide were 6.8, 270 and 2.5 gm/m 2 respectively. Two patients received radiotherapy [rhabdomyosarcoma (50 Gy), synovial sarcoma (45 Gy)]. The median latency period to develop t-AML/MDS was 24 months (range 16.5-62 months). Most common FAB morphology was M4/M5 (7/8) and cytogenetic abnormality was MLL rearrangement (4/8). Five patients opted for treatment, 4 achieved remission out of which 2 patients are alive and disease free. Short latency periods, absence of pre-leukemic phase and 11q23 translocations were characteristic in the patients with t-AML/MDS. In view of poor outcome with conventional therapy, novel strategies and prevention need to be considered.

  12. MDS clinical diagnostic criteria for Parkinson's disease in China.

    Science.gov (United States)

    Li, Jun; Jin, Miao; Wang, Li; Qin, Bin; Wang, Kang

    2017-03-01

    The Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (MDS-PD Criteria) was introduced by the Movement Disorder Society in 2015 for research purposes. However, its use for clinical diagnosis of Parkinson disease still needs further revision. This study compares the UK-Criteria versus MDS-PD Criteria in the clinical diagnosis of Parkinson disease referred to the China-Japan Friendship Hospital of Beijing, China. To compare the MDS-PD Criteria with the UK-Criteria and discuss the feasibility of the clinical application of MDS-PD Criteria as a general guide to clinical diagnosis of PD in Chinese PD patients. 150 patients of neurology clinic of China-Japan Friendship Hospital of Beijing were recruited in our research. They were divided into three groups: UK-Criteria group, MDS-PD Criteria group and a combined group of UK and MDS-PD Criteria. Clinical history was collected while physical and auxiliary examinations were done by a trained neurologist according to the corresponding criteria. An interrater reliability analysis using the Kappa statistic claimed substantial agreement (κ = 0.626) between the MDS-PD Criteria and the UK-Criteria. The differences between the diagnostic results of these two criteria were statistically significant by paired Chi-square test (p = 0.000). It was found that levodopa-induced dyskinesia had a good positive predictive value, while early bulbar impairment and inspiratory dysfunction presented a negative predictive value. The MDS-PD Criteria emphasize the importance of non-motor symptoms, keeping the motor symptoms as the core for the clinical diagnosis of PD, and establish categories of diagnosis features and levels of certainty which are more complete and organized to be used and replicated by non specialized physicians to evaluated patients with Parkinsonism. The higher sensitivity of MDS-PD Criteria compared with UK-Criteria is worth being widely used in clinical work.

  13. CONIFER - Non-Interventional Study to Evaluate Therapy Monitoring During Deferasirox Treatment of Iron Toxicity in Myelodysplastic Syndrome Patients with Transfusional Iron Overload.

    Science.gov (United States)

    Bruch, Harald-Robert; Dencausse, Yves; Heßling, Jörg; Michl, Gerlinde; Schlag, Rudolf; Skorupa, Alexandra; Schneider-Schranz, Cornelia; Wolf, Sebastian; Schulte, Clemens; Tesch, Hans

    2016-01-01

    The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients. Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up. The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated. The mean age of the participants was 75 years and 58% of the patients were male. Iron overload was assessed by serum ferritin level (mean baseline serum ferritin 2,080 ± 1,244 µg/l). Patients were treated for a mean duration of 16 months (mean daily dose at baseline 11.8 ± 7.0 mg/kg). Stratification of serum ferritin levels by deferasirox dose showed a reduction at the higher but no reduction at the lower dose (deferasirox effectively and safely reduced serum ferritin levels in MDS patients with transfusional iron overload. © 2016 S. Karger GmbH, Freiburg.

  14. Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease.

    Science.gov (United States)

    Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P

    2015-01-01

    The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS-UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS-UPDRS non-motor items and QoL. A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS-UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 ± 9.0 years, 53.5% were men, mean disease duration was 8.3 ± 5.3 years and mean HY was 2.7 ± 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS-UPDRS parts II, I and IV respectively, but not to part III. Individual MDS-UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS-UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains. The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS-UPDRS non-motor items related to worse QoL are especially pain and other sensations, fatigue and features of DDS. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy.

    Science.gov (United States)

    Damman, Peter; Kempf, Tibor; Windhausen, Fons; van Straalen, Jan P; Guba-Quint, Anja; Fischer, Johan; Tijssen, Jan G P; Wollert, Kai C; de Winter, Robbert J; Hirsch, Alexander

    2014-03-15

    No five-year long-term follow-up data is available regarding the prognostic value of GDF-15. Our aim is to evaluate the long-term prognostic value of admission growth-differentiation factor 15 (GDF-15) regarding death or myocardial infarction (MI) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). This is a subanalysis from the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial, including troponin positive NSTE-ACS patients. The main outcome for the current analysis was 5-year death or spontaneous MI. GDF-15 samples were available in 1151 patients. The prognostic value of GDF-15, categorized into 1800 ng/L, was assessed in unadjusted and adjusted Cox regression models. Adjustments were made for identified univariable risk factors. The additional discriminative and reclassification value of GDF-15 beyond the independent risk factors was assessed by the category-free net reclassification improvement (1/2 NRI(>0)) and the integrated discrimination improvement (IDI) RESULTS: Compared to GDF-151800 ng/L was associated with an increased hazard ratio for death or spontaneous MI, mainly driven by mortality. GDF-15 levels were predictive after adjustments for other identified predictors. Additional discriminative value was shown with the IDI, not with the NRI. In patients presenting with NSTE-ACS and elevated troponin T, GDF-15 provides prognostic information in addition to identified predictors for mortality and spontaneous MI and can be used to identify patients at high risk during long-term follow-up. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Resident Assessment Instrument/Minimum Data Set (RAI/MDS)

    Data.gov (United States)

    Department of Veterans Affairs — The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) is a comprehensive assessment and care planning process used by the nursing home industry since 1990 as...

  17. MDS 2.0 Public Quality Indicator and Resident Reports

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Minimum Data Set (MDS) is part of the federally mandated process for clinical assessment of all residents in Medicare or Medicaid certified nursing homes. This...

  18. Gene-Specific Demethylation as Targeted Therapy in MDS

    Science.gov (United States)

    2017-07-01

    AWARD NUMBER: W81XWH-15-1-0161 TITLE: Gene-Specific Demethylation as Targeted Therapy in MDS PRINCIPAL INVESTIGATOR: Daniel G. Tenen, M.D...15JUN2016-14JUN2017 4. TITLE AND SUBTITLE Gene-Specific Demethylation as Targeted Therapy in MDS 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM... magnetic beads capture all newly synthesized transcripts. To compare the transcriptional profiles under these conditions with our previous results, we

  19. New constructions of MDS codes with complementary duals

    OpenAIRE

    Chen, Bocong; Liu, Hongwei

    2017-01-01

    Linear complementary-dual (LCD for short) codes are linear codes that intersect with their duals trivially. LCD codes have been used in certain communication systems. It is recently found that LCD codes can be applied in cryptography. This application of LCD codes renewed the interest in the construction of LCD codes having a large minimum distance. MDS codes are optimal in the sense that the minimum distance cannot be improved for given length and code size. Constructing LCD MDS codes is thu...

  20. An improved resource management model based on MDS

    Science.gov (United States)

    Yuan, Man; Sun, Changying; Li, Pengfei; Sun, Yongdong; He, Rui

    2005-11-01

    GRID technology provides a kind of convenient method for managing GRID resources. This service is so-called monitoring, discovering service. This method is proposed by Globus Alliance, in this GRID environment, all kinds of resources, such as computational resources, storage resources and other resources can be organized by MDS specifications. However, this MDS is a theory framework, particularly, in a small world intranet, in the case of limit of resources, the MDS has its own limitation. Based on MDS, an improved light method for managing corporation computational resources and storage resources is proposed in intranet(IMDS). Firstly, in MDS, all kinds of resource description information is stored in LDAP, it is well known although LDAP is a light directory access protocol, in practice, programmers rarely master how to access and store resource information into LDAP store, in such way, it limits MDS to be used. So, in intranet, these resources' description information can be stored in RDBMS, programmers and users can access this information by standard SQL. Secondly, in MDS, how to monitor all kinds of resources in GRID is not transparent for programmers and users. In such way, it limits its application scope, in general, resource monitoring method base on SNMP is widely employed in intranet, therefore, a kind of resource monitoring method based on SNMP is integrated into MDS. Finally, all kinds of resources in the intranet can be described by XML, and all kinds of resources' description information is stored in RDBMS, such as MySql, and retrieved by standard SQL, dynamic information for all kinds of resources can be sent to resource storage by SNMP, A prototype resource description, monitoring is designed and implemented in intranet.

  1. Allogeneic stem cell transplantation for older advanced MDS patients: improved survival with young unrelated donor in comparison with HLA-identical siblings

    NARCIS (Netherlands)

    Kroger, N.; Zabelina, T.; Wreede, L. de; Berger, J.; Alchalby, H.; Biezen, A. van; Milpied, N.; Volin, L.; Mohty, M.; Leblond, V.; Blaise, D.; Finke, J.; Schaap, N.P.; Robin, M.; Witte, T.J. de

    2013-01-01

    We investigated whether a young human leukocyte antigen (HLA)-matched unrelated donor (MUD) should be preferred as donor to an HLA-identical sibling (MRD) for older patients with myelodysplastic syndrome (MDS) (>/=50 years) who underwent allogeneic stem cell transplantation (AHSCT). Outcomes of 719

  2. Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk myelodysplastic syndromes: a retrospective, multicentre study.

    Science.gov (United States)

    Musto, Pellegrino; Maurillo, Luca; Simeon, Vittorio; Poloni, Antonella; Finelli, Carlo; Balleari, Enrico; Ricco, Alessandra; Rivellini, Flavia; Cortelezzi, Agostino; Tarantini, Giuseppe; Villani, Oreste; Mansueto, Giovanna; Milella, Maria R; Scapicchio, Daniele; Marziano, Gioacchino; Breccia, Massimo; Niscola, Pasquale; Sanna, Alessandro; Clissa, Cristina; Voso, Maria T; Fenu, Susanna; Venditti, Adriano; Santini, Valeria; Angelucci, Emanuele; Levis, Alessandro

    2017-06-01

    Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75). Eight patients (16%) showed grade 2-3 toxicities (renal or gastrointestinal), 4 of whom (8%) required drug interruption. Median ferritin levels decreased from 1709 μg/l at baseline to 1100 μg/l after 12 months of treatment (P = 0·02). Seventeen patients showed abnormal transaminase levels at baseline, which improved or normalized under DFX treatment in eight cases. One patient showed a remarkable haematological improvement. At a median follow up of 35·3 months, median overall survival was 37·5 months. The results of this first survey of DFX in HR-MDS are comparable, in terms of safety and efficacy, with those observed in lower-risk MDS. Though larger, prospective studies are required to demonstrate real clinical benefits, our data suggest that DFX is feasible and might be considered in a selected cohort of HR-MDS patients. © 2017 John Wiley & Sons Ltd.

  3. Transcranial Magnetic Stimulation (TMS) as a Tool for Early Diagnosis and Prognostication in Cortico-Basal Ganglia Degeneration (CBD) Syndromes: Review of Literature and Case Report.

    Science.gov (United States)

    Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Nagaraju, B C

    2016-01-01

    Cortico basal degeneration (CBD) of the brain is a rare progressive neurodegenerative disease which encompasses unique neuropsychiatric manifestations. Early diagnosis is essential for initiating proper treatment and favorable outcome. Transcranial Magnetic Stimulation (TMS), a well-known technique for assessment of cortical excitatory and inhibitory properties. It was suggested that in a degenerative disease like CBD which involves the cortex as well as the subcortical structures, comparing both hemispheres, a differential pattern in TMS can be obtained which would help in early identification, prognostication and early therapeutic intervention. We describe a case of CBD with corroborative clinical and imaging picture wherein single pulse TMS was used over both the hemispheres measuring the following parameters of interest which included: Motor Threshold (MT), Central Motor Conduction Time (CMCT) and Silent Period (SP). Differential patterns of MT, CMCT and SP was obtained by stimulating over both the hemispheres with the affected hemisphere showing significantly reduced MT and prolonged CMCT implying early impairment of cortical and subcortical structures thereby revealing the potential application of TMS being utilized in a novel way for early detection and prognostication in CBD syndromes.

  4. Incremental prognostic value of cardiac function assessed by ECG-gated myocardial perfusion SPECT for the prediction of future acute coronary syndrome

    International Nuclear Information System (INIS)

    Matsumoto, Naoya; Sato, Yuichi; Suzuki, Yasuyuki

    2008-01-01

    The prognostic value of electrocardiogram (ECG)-gated rest 201 T1/stress 99m Tc-tetrofosmin myocardial perfusion single-photon emission computed tomography for the prediction of acute coronary syndrome (ACS: myocardial infarction (MI) and unstable angina (UA)) and the implications of ejection fraction (EF) has not yet been defined in Japanese. The 1,895 patients were followed up for the occurrence ACS. The mean follow-up interval was 26.9±15.5 months. The 142 patients with revascularization within 60 days were censored. Summed stress score (SSS) and summed difference score (SDS) were calculated. The 19 MI and 29 UA occurred (1.1% and 1.6%, respectively). Univariate Cox analysis showed that hypertension (Wald 5.09, p<0.05), poststress EF (Wald 10.9, p<0.01), SSS (Wald 12.4, p<0.001) and SDS (Wald 18.7, p<0.001) were significant predictors of ACS. Multivariate Cox analysis showed that hypertension (Wald 4.27, p<0.05) and SDS (Wald 8.59, p<0.01) were independent predictors. When multiple clinical risk factors (number of coronary risk factors ≥2), significant ischemia (SDS≥4) and low EF (EF<45%) were applied to multivariate Cox analysis, the combination of significant ischemia and low EF showed the highest predictive value (Wald 11.9; p<0.001) for future ACS. Poststress EF added incremental prognostic value for the prediction of ACS. (author)

  5. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes.

    Science.gov (United States)

    Germing, Ulrich; Strupp, Corinna; Kuendgen, Andrea; Isa, Shadi; Knipp, Sabine; Hildebrandt, Barbara; Giagounidis, Aristoteles; Aul, Carlo; Gattermann, Norbert; Haas, Rainer

    2006-12-01

    The aim of this study was a prospective validation of the World Health Organization (WHO) proposals for the classification of myelodysplastic syndromes (MDS) with respect to their prognostic relevance. We classified 1095 patients with MDS diagnosed at our institution between November 1999 and December 2004 according to French-American-British (FAB) and WHO criteria by central morphologic review. The study was not population-based, but included all newly diagnosed patients from different regions in Germany. Patients were followed for survival and disease evolution to acute myeloid leukemia (AML) through December 31th, 2005. According to the WHO classification, there were 89 cases of refractory anemia (RA), 293 of refractory cytopenias with multilineage dysplasia (RCMD), 31 RA with ringed sideroblasts (RARS), 139 RCMD with ringed sideroblasts (RCMD-RS), 142 RA with excess blasts (RAEB) I and 149 RAEB II and 52 patients with 5q- syndrome. The median survival of patients with RA or RARS was not reached, the median survival of patients with RCMD was 31 months, that of patients with RCMD-RS was 28 months, that of 5q- patients was 40 months, of RAEB I 27 months and of RAEB II 12 months. The cumulative risk of AML evolution 2 years after diagnosis was 0% in RA and RARS, 8% in 5q-, 9% in RCMD, 12% in RCMD-RS, 13% in RAEB I and 40% in RAEB II. The number of high-risk karyotypes was lower in patients with RA/RARS than in those with RCMD/RCMD-RS and RAEB I/RAEB II. Karyotype findings were major prognostic variables. The WHO classification is feasible and provides valuable prognostic information, even in a short-term prospective study. Together with cytogenetic data and other prognostic parameters, the WHO classification is very useful for clinical decision making.

  6. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country.

    Science.gov (United States)

    Velloso, E D R P; Chauffaille, M L; Peliçario, L M; Tanizawa, R S S; Toledo, S R C; Gaiolla, R D; Lopes, L F

    2013-01-01

    Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

  7. Monitoring the grid with the Globus Toolkit MDS4

    International Nuclear Information System (INIS)

    Schopf, Jennifer M; Pearlman, Laura; Miller, Neill; Kesselman, Carl; Foster, Ian; D'Arcy, Mike; Chervenak, Ann

    2006-01-01

    The Globus Toolkit Monitoring and Discovery System (MDS4) defines and implements mechanisms for service and resource discovery and monitoring in distributed environments. MDS4 is distinguished from previous similar systems by its extensive use of interfaces and behaviors defined in the WS-Resource Framework and WS-Notification specifications, and by its deep integration into essentially every component of the Globus Toolkit. We describe the MDS4 architecture and the Web service interfaces and behaviors that allow users to discover resources and services, monitor resource and service states, receive updates on current status, and visualize monitoring results. We present two current deployments to provide insights into the functionality that can be achieved via the use of these mechanisms

  8. Prognostic value of metabolic syndrome for the development of cardiovascular disease in a cohort of premenopausal women with systemic lupus erythematosus.

    Science.gov (United States)

    García-Villegas, Elsy Aidé; Lerman-Garber, Israel; Flores-Suárez, Luis Felipe; Aguilar-Salinas, Carlos; Márquez González, Horacio; Villa-Romero, Antonio Rafael

    2015-04-08

    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. In lupus patients there is an increased cardiovascular risk due to an accelerated atherogenesis. Furthermore, Metabolic Syndrome (MS) adds an independent risk for developing Cardiovascular Disease (CVD) in the population. Therefore, it is important to determine whether lupus patients have an increased risk of developing Cardiovascular Disease in the presence of MS. To estimate the prognostic value of MS in the incidence of cardiovascular events in a cohort of premenopausal patients with SLE. Cohort study in 238 patients was carried out. Clinical, biochemical, dietetic and anthropometric evaluations were performed. Patients were classified according to the prevalence of MS in 2001. There was a patient follow-up from 2001 to 2008. In 2008, after studying the records, we obtained the "cases" (patients with CVD) and the "no cases" (patients without CVD). The basal prevalence of MS in the cohort was of 21.8% (ATPIII). The MS component with the highest prevalence in the population studied in 2001 was low HDL-Cholesterol (<50mg/dL) with a prevalence of 55.0%. The cumulative incidence of CVD in the group with MS was 17.3% and in the group without MS it was 7.0% with a Relative Risk (RR) of 2.48 (1.12-5.46) and p<0.05. In the multivariable analysis it was noted that MS is a predictive factor of CVD. We observed the prognostic value of MS for an increased risk of cardiovascular damage in premenopausal patients with lupus. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis

    International Nuclear Information System (INIS)

    Wattjes, Mike P.; Harzheim, Michael; Schmidt, Stephan; Lutterbey, Goetz G.; Schild, Hans H.; Traeber, Frank; Bogdanow, Manuela

    2008-01-01

    The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3-4 and 6-7 months after the initial event. Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (-13.4%, P = 0.002) whereas nonconverters (-6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS. (orig.)

  10. The MDS challenging behavior profile for long-term care

    NARCIS (Netherlands)

    Gerritsen, D. L.; Achterberg, W. P.; Steverink, N.; Frijters, D. H. M.; Ribbe, M. W.

    2008-01-01

    The objective was to construct a reliable and valid challenging behavior scale with items from the Minimum Data Set (MDS). Exploratory factor analyses of a sample of 656 nursing home residents yielded a 16-item Behavior Profile containing four internally consistent and valid subscales measuring

  11. Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Chen, T-C; Hou, H-A; Chou, W-C; Tang, J-L; Kuo, Y-Y; Chen, C-Y; Tseng, M-H; Huang, C-F; Lai, Y-J; Chiang, Y-C; Lee, F-Y; Liu, M-C; Liu, C-W; Liu, C-Y; Yao, M; Huang, S-Y; Ko, B-S; Hsu, S-C; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2014-01-01

    Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression

  12. Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1 Gene Expression in Egyptian Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nadia El Menshawy

    2014-06-01

    Full Text Available OBJECTIVE: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1 gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic significance in those patients. METHODS: Using quantitative real-time polymerase chain reaction for detection of LYL1 oncogenes, our study was carried out on 39 myeloid leukemia patients including de novo cases, myelodysplastic syndrome (MDS with transformation, and chronic myelogenous leukemia (CML in accelerated and blast crisis, in addition to 10 healthy individuals as the reference control. RESULTS: LYL1 expression was increased at least 2 times compared to the controls. The highest expression of this transcription factor was observed in the MDS cases transformed to acute leukemia at 7.3±3.1, p=0.0011. LYL1 expression was found in 68.2%, 75%, and 77.8% of cases of acute myeloid leukemia, CML crisis, and MDS, respectively. Significant correlation of LYL1 overexpression with some subtypes of French-American-British classification was found. There was, for the first time, significant correlation between the blood count at diagnosis and LYL1 expression (p=0.023, 0.002, and 0.031 for white blood cells, hemoglobin, and platelets, respectively. The rate of complete remission was lower with very high levels of LYL1 expression and the risk of relapse increased with higher levels of LYL1 expression, suggesting an unfavorable prognosis for cases with enhanced expression. CONCLUSION: Overexpression of LYL1 is highly associated with acute myeloid leukemia and shows more expression in MDS with unfavorable prognosis in response to induction chemotherapy. These

  13. 75 FR 16512 - Willstaff Staffing Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., Working...

    Science.gov (United States)

    2010-04-01

    ... Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., Working On-Site at Tyler Pipe... MDS Industrial Resources, Inc., working on-site at Tyler Pipe Company, Waterworks Division, South... Staffing Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., working on-site at Tyler Pipe...

  14. Some Families of Asymmetric Quantum MDS Codes Constructed from Constacyclic Codes

    Science.gov (United States)

    Huang, Yuanyuan; Chen, Jianzhang; Feng, Chunhui; Chen, Riqing

    2018-02-01

    Quantum maximal-distance-separable (MDS) codes that satisfy quantum Singleton bound with different lengths have been constructed by some researchers. In this paper, seven families of asymmetric quantum MDS codes are constructed by using constacyclic codes. We weaken the case of Hermitian-dual containing codes that can be applied to construct asymmetric quantum MDS codes with parameters [[n,k,dz/dx

  15. Handling missing values in the MDS-UPDRS.

    Science.gov (United States)

    Goetz, Christopher G; Luo, Sheng; Wang, Lu; Tilley, Barbara C; LaPelle, Nancy R; Stebbins, Glenn T

    2015-10-01

    This study was undertaken to define the number of missing values permissible to render valid total scores for each Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part. To handle missing values, imputation strategies serve as guidelines to reject an incomplete rating or create a surrogate score. We tested a rigorous, scale-specific, data-based approach to handling missing values for the MDS-UPDRS. From two large MDS-UPDRS datasets, we sequentially deleted item scores, either consistently (same items) or randomly (different items) across all subjects. Lin's Concordance Correlation Coefficient (CCC) compared scores calculated without missing values with prorated scores based on sequentially increasing missing values. The maximal number of missing values retaining a CCC greater than 0.95 determined the threshold for rendering a valid prorated score. A second confirmatory sample was selected from the MDS-UPDRS international translation program. To provide valid part scores applicable across all Hoehn and Yahr (H&Y) stages when the same items are consistently missing, one missing item from Part I, one from Part II, three from Part III, but none from Part IV can be allowed. To provide valid part scores applicable across all H&Y stages when random item entries are missing, one missing item from Part I, two from Part II, seven from Part III, but none from Part IV can be allowed. All cutoff values were confirmed in the validation sample. These analyses are useful for constructing valid surrogate part scores for MDS-UPDRS when missing items fall within the identified threshold and give scientific justification for rejecting partially completed ratings that fall below the threshold. © 2015 International Parkinson and Movement Disorder Society.

  16. Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease.

    Science.gov (United States)

    Tobiasson, Magnus; Abdulkadir, Hani; Lennartsson, Andreas; Katayama, Shintaro; Marabita, Francesco; De Paepe, Ayla; Karimi, Mohsen; Krjutskov, Kaarel; Einarsdottir, Elisabet; Grövdal, Michael; Jansson, Monika; Ben Azenkoud, Asmaa; Corddedu, Lina; Lehmann, Sören; Ekwall, Karl; Kere, Juha; Hellström-Lindberg, Eva; Ungerstedt, Johanna

    2017-04-25

    Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3. Interestingly, we observed activation of transcripts containing 15 endogenous retroviruses (ERVs) confirming previous cell line studies. DNA methylation decreased moderately in 99% of all genes, with a median β-value reduction of 0.018; the most pronounced effects seen in heterochromatin. Aza-induced hypomethylation correlated significantly with change in H3K9me3. The pattern of H3K18ac and H3K9me3 displayed large differences between patients and healthy controls without any consistent pattern induced by Aza. We conclude that the marked induction of gene expression only partly could be explained by epigenetic changes, and propose that activation of ERVs may contribute to the clinical effects of Aza in MDS.

  17. Monosomal karyotype predicts inferior survival independently of a complex karyotype in patients with myelodysplastic syndromes.

    Science.gov (United States)

    McQuilten, Zoe K; Sundararajan, Vijaya; Andrianopoulos, Nick; Curtis, David J; Wood, Erica M; Campbell, Lynda J; Wall, Meaghan

    2015-09-01

    Conflicting data exist about the impact of a monosomal karyotype (MK) on overall survival (OS) for patients with myelodysplastic syndromes (MDSs) and particularly for those with a complex karyotype (CK). This study was aimed at determining whether an MK is associated with OS independently of the number of cytogenetic abnormalities (CAs) in a population-based MDS cohort. Cancer registry data on incident MDS cases were linked with cytogenetic data and hospital administrative data from 2000 to 2010 for the Australian state of Victoria. Between 2000 and 2010, 1404 incident MDS cases with cytogenetic results were identified. A CK, defined as 3 or more abnormalities, was present in 126 (9%). A very complex karyotype (vCK), defined as 5 or more abnormalities, was present in 95 (7%). An MK was associated with worse OS in the whole cohort (median 6 vs 39 months, P < 0.001) including those with a coexisting CK (6 vs 17 months, P < 0.001) or vCK (6 vs 9 months, P = 0.02). After adjustments for the number of CAs, an MK remained independently associated with OS, although its effect size decreased with increasing cytogenetic complexity (hazard ratio for an MK, 4.81; 95% confidence interval, 3.08-7.52; hazard ratio for the number of CAs, 1.22; 95% confidence interval, 1.15-1.30; and hazard ratio for the interaction between an MK and CAs, 0.83; 95% confidence interval, 0.77-0.89). These results support the clinical utility of an MK as an independent predictor of adverse outcomes for MDS patients, even among CK and vCK groups, although its prognostic effect decreases with increasing cytogenetic complexity. © 2015 American Cancer Society.

  18. Similar Transplant Outcomes for AML/MDS Patients with Haploidentical versus 10/10 HLA Matched Unrelated and Related Donors

    Science.gov (United States)

    Di Stasi, Antonio; Milton, Denái R.; Poon, LM; Hamdi, Amir; Rondon, Gabriela; Chen, Julianne; Pingali, Sai R.; Konopleva, Marina; Kongtim, Piyanuch; Alousi, Amin; Qazilbash, Muzaffar H.; Ahmed, Sairah; Bashir, Qaiser; Al-atrash, Gheath; Oran, Betul; Hosing, Chitra M.; Kebriaei, Partow; Popat, Uday; Shpall, Elizabeth J.; Lee, Dean A.; de Lima, Marcos; Rezvani, Katayoun; Khouri, Issa F.; Champlin, Richard E.; Ciurea, Stefan O.

    2015-01-01

    Allogeneic stem-cell transplantation for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has been performed primarily with an HLA matched donor. Outcomes of haploidentical transplantation have recently improved, and a comparison between these donor sources in a uniform cohort of patients has not been performed. We evaluated outcomes of 227 patients with AML/MDS treated with melphalan-based conditioning. Donors were matched related (MRD) (N=87, 38%), matched unrelated (MUD) (N=108, 48%), or haploidentical (N=32, 14%). No significant differences were found between haploidentical and MUD transplant outcomes; however, there was a trend for improved outcomes in the MRD group with a 3-year progression-free survival for patients in remission of 57%, 45% and 41% for MRD, MUD and haploidentical, respectively (P=0.417). Recovery of T-cell subsets was similar for all groups. These results suggest that haploidentical donors can safely extend transplantation for AML/MDS patients without an HLA matched donor. Prospective studies comparing haploidentical and MUD transplants are warranted. PMID:25263628

  19. Prognostic Utility of Computed Tomography Histogram Analysis in Patients With Post-Cardiac Arrest Syndrome: Evaluation Using an Automated Whole-Brain Extraction Algorithm.

    Science.gov (United States)

    Yamashita, Koji; Hiwatashi, Akio; Kondo, Masatoshi; Togao, Osamu; Kikuchi, Kazufumi; Sugimori, Hiroshi; Yoshiura, Takashi; Honda, Hiroshi

    2016-01-01

    The aim of the study was to evaluate the prognostic utility of computed tomography (CT) histogram analysis with an automated whole-brain extraction algorithm in patients with post-cardiac arrest syndrome (PCAS). Computed tomography data from consecutive patients between January 2009 and February 2012 were obtained and retrospectively analyzed. All CT images were obtained using a 64-detector-row CT scanner with a slice thickness of 4.0 mm. A brain region was extracted from the whole-brain CT images using our original automated algorithm and used for the subsequent histogram analysis. The obtained histogram statistics (mean brain tissue CT value, kurtosis, and skewness), as well as clinical parameters, were compared between the good and poor outcome groups using the Student t test. In addition, receiver operating characteristic curve analysis was performed for the discrimination between the 2 groups for each parameter. One hundred thirty-eight consecutive PCAS patients were enrolled. The patients were classified into good (n = 47) and poor (n = 91) outcome groups. The mean brain tissue CT value was significantly higher in the good outcome group than in the poor outcome group (P brain tissue CT value, skewness, and age were 0.751, 0.639, 0.623, and 0.626, respectively. A combination of the 4 parameters increased the diagnostic performance (area under the curve = 0.814). Histogram analysis of whole-brain CT images with our automated extraction algorithm is useful for assessing the outcome of PCAS patients.

  20. Lille Apathy Rating Scale and MDS-UPDRS for Screening Apathy in Parkinson's Disease.

    Science.gov (United States)

    Weintraut, Rita; Karádi, Kázmér; Lucza, Tivadar; Kovács, Márton; Makkos, Attila; Janszky, József; Kovács, Norbert

    2016-01-01

    Apathy is a syndrome characterized primarily by lack of motivation which may be associated with cognitive, affective and behavioral changes. Although the Lille Apathy Scale (LARS) has been extensively utilized in PD for detecting apathy and testing the effectiveness of specific therapeutic interventions, the highly variable cut-off values (between -11 and -22 points) ensures the applicability of the LARS degree of difficulty as a superb screening tool. The aim of this study is to determine more reliable threshold values based on the neuropsychiatric status of patients. Depression was assessed utilizing the Montgomery-Asberg Depression Rating Scale and neurocognitive status by Addenbrooke's Cognitive Examination. The presence of apathy was assessed by the proposed diagnostic criteria of Drijgers et al, and graded by both LARS and the 'Apathy' item of MDS-UPDRS. Based on multivariate regression analysis, we revealed the neurocognitive status, severity of depression, and also gender while applying dosage of dopamine agonists to determine the degree of patient apathy. Based on whether or not depression and neurocognitive disorders were indeed present, we established four different threshold values for the LARS: patients with normal cognition and without depression: -22.5; patients with normal cognition and with depression: -18.5; patients with NCD and without depression: -19.5; patients with NCD and with depression: -14.5. The LARS and the 'Apathy' item of MDS-UPDRS were confirmed to be potentially operational, beneficial and easy-to-assess instruments for detecting apathy syndrome in PD. However, there is no universal threshold value for the LARS suitable in all types of Parkinson's patients.

  1. Entanglement-assisted quantum MDS codes from negacyclic codes

    Science.gov (United States)

    Lu, Liangdong; Li, Ruihu; Guo, Luobin; Ma, Yuena; Liu, Yang

    2018-03-01

    The entanglement-assisted formalism generalizes the standard stabilizer formalism, which can transform arbitrary classical linear codes into entanglement-assisted quantum error-correcting codes (EAQECCs) by using pre-shared entanglement between the sender and the receiver. In this work, we construct six classes of q-ary entanglement-assisted quantum MDS (EAQMDS) codes based on classical negacyclic MDS codes by exploiting two or more pre-shared maximally entangled states. We show that two of these six classes q-ary EAQMDS have minimum distance more larger than q+1. Most of these q-ary EAQMDS codes are new in the sense that their parameters are not covered by the codes available in the literature.

  2. Impact of Cytogenetics on Outcome of De novo and Therapy-related AML and MDS after Allogeneic Transplantation

    Science.gov (United States)

    Armand, Philippe; Kim, Haesook T.; DeAngelo, Daniel J.; Ho, Vincent T.; Cutler, Corey S.; Stone, Richard M.; Ritz, Jerome; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.

    2009-01-01

    Cytogenetics has an important impact on the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for AML or MDS. However, it is unclear whether currently accepted cytogenetic risk groups, which were established for patients treated mostly with standard therapy, are optimally discriminating for patients undergoing HSCT. Also, the impact of cytogenetics in the growing population of patients with therapy-related disease has not been completely elucidated. In this study, we retrospectively analyzed data on 556 patients with AML or MDS transplanted at our institution. We examined, in multivariate analyses, the contribution of cytogenetics to survival, relapse, and non-relapse mortality (NRM) for the 476 patients with de novo disease. We used these results to establish an optimal cytogenetic grouping scheme. We then applied this grouping scheme to the 80 patients with therapy-related disease. Our proposed three-group cytogenetic classification outperformed the established grouping schemes for both de novo and therapy-related disease. When classified by this new scheme, cytogenetics was the strongest prognostic factor for overall survival in our cohort, through its impact on the risk of relapse (and not on NRM). After accounting for cytogenetics, patients with therapy-related AML or MDS had an equivalent outcome to those with de novo disease. This study demonstrates the impact of cytogenetics on the risk of relapse and death for patients with both de novo and therapy-related disease undergoing transplantation; it also emphasizes the necessity of using cytogenetics to stratify patients entering clinical trials, and provides a system for doing so, which can be validated in a multi-institutional database. PMID:17531775

  3. The clinical, haematological and morphological profile of patients with myelodysplastic syndromes: a single institution experience from Turkey.

    Science.gov (United States)

    Demirkan, Fatih; Alacacioglu, Inci; Piskin, Ozden; Ozsan, Hayri G; Akinci, Baris; Ozcan, Ali M; Yavuzsen, Tugba; Yuksel, Erdinc; Undar, Bulent

    2007-07-01

    In a retrospective analysis of 113 patients with primary myelodysplastic syndromes (MDS) diagnosed according to French-American-British (FAB) classification, we evaluated the prognostic impact of FAB and World Health Organisation (WHO) classifications, International Prognostic Scoring System (IPSS), and other clinical and laboratory variables. The median age was 69. IPSS could be applied to 75 patients classified according to the FAB criteria and to 50 patients reclassified according to the WHO criteria. At a median follow-up of 24 months, 22 patients (19.5 %) transformed to acute myelogenous leukaemia (AML). Overall survival (OS) of patients differed significantly between the FAB and WHO subgroups (p WHO classification, significant differences were observed in both OS and leukaemia free survival (LFS) between patients with RA/RARS and refractory cytopenia with multi-lineage dysplasia/refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD/RS-RCMD) (p = 0.0001). High-risk according to IPSS score and blood transfusion need were significantly predictive for a shorter survival and higher risk of transformation. Hemoglobin WHO classification for prediction of prognosis in MDS.

  4. Prognostic factors for carcinoma of unknown primary localized to the neck only (CUP Syndrome) and the role of F-18-FDG PET for diagnosis and therapeutic management

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Niesen, A.; Bank, P.; Lopatta, E.C.; Wendt, T.G.; Koscielny, S.; Beleites, E.

    2002-01-01

    Aim: Treatment of patients with carcinoma of unknown primary localized to the neck only is still controversial. To determine both patient related prognostic factors and the influence of treatment parameters the records of 99 patients were analyzed retrospectively, to evaluate the role of F-18-FDG PET for diagnostics and therapy management 33 patients were analyzed prospectively. Material and Methods: Retrospectively: Out of 99 patients with carcinoma of unknown primary, 51 received surgery as a sole treatment. 48 were treated with a combination of surgery and radiation therapy. 8/99 patients received a F-18-FDG PET. Statistical analyses: Kaplan-Meier, log-rank-test, chi-square-test. Prospectively: All PET studies were carried out after conventional diagnostic procedures failed to detect the primary tumor. PET findings were correlated with histology and/or clinical course of the patients. Results: Retrospectively: Disease specific survival (DSS) was significant longer for patients with N1/N2 vs. N3 (p=0.03), for upper nodal involvement vs. lower and/or supraclavicular nodal involvement (p=0.031) and for absence of extracapsular spread (p=0.041). No influence of DSS was noted for grading (p=0.469), treatment volume (p=0.82) and applied dose (>50Gy vs. <50Gy). In 2/8 patients, PET detected the primary tumor, in 1/8 bone metastases. Prospectively: Detection of the primary tumor by PET was successful in 21%, mostly in patients with lower and/or supraclavicular nodal involvement. In these patients the primary tumor was located extracervically in 72%, e.g. lung or gastric cancer. Distant metastases were detected in 33%. Conclusion: The presence of ECS, the extend and localization of nodal involvement are prognostic factors in patients suffering from CUP localized to the neck only. Patients with upper nodal involvement should be treated with curative intention. The irradiation fields should cover the whole neck including the potential region of the primary tumor with doses

  5. Venous lactate, pH and partial pressure of carbon dioxide levels as prognostic indicators in 110 premature calves with respiratory distress syndrome.

    Science.gov (United States)

    Yildiz, R; Aydogdu, U; Guzelbektes, H; Coskun, A; Sen, I

    2017-06-24

    Hyperlactatemia, hypercapnia, low pH and low oxygen saturation (SatO 2 ) are commonly observed in premature calves. These clinical indicators are associated with increased mortality in preterm human newborns with respiratory distress syndrome (RDS). The aim of this study was to investigate the prognostic importance of venous pH, partial pressure of carbon dioxide (pCO 2 ) and lactate level and which parameters are related with mortality in premature calves with RDS. All premature calves (52 male/58 female) were admitted to clinic within 12-24 hours after birth and blood samples were also taken into heparinised plastic syringes from the jugular vein within 30 minutes following admission. Diagnosis of RDS was made by both clinical signs and blood gas results. For the evaluation of independent samples, t test was used to compare the venous blood gas indicators of surviving and non-surviving premature calves. Receiver operating characteristics curves were used to determine a cut-off value in terms of lactate and pCO 2 measurements among non-surviving and surviving calves. Venous pH, pCO 2 , SatO 2 , base deficit, bicarbonate (HCO 3 ) and lactate levels showed a significant variance between surviving and non-surviving calves. Mean venous pH, pCO 2 , SatO 2 , lactate levels in non-surviving premature calves was 7.05, 78.9 mm Hg, 16.1 per cent and 9.50 mmol/l, respectively. Mean pH, pCO 2 , SatO 2 and lactate levels in surviving premature calves were 7.29, 56.3 mm Hg, 25.5 per cent and 5.1 mmol/l, respectively. The cut-off values for lactate and pCO 2 were 7.5 mmol/l and 63.5 mm Hg, respectively. In conclusion, the results of the study show that venous blood lactate and pCO 2 have prognostic importance in premature calves with RDS. British Veterinary Association.

  6. MECP2 Duplication Syndrome

    DEFF Research Database (Denmark)

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients...... and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy...... condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were...

  7. Prognostic value of blood glucose levels in diabetic patients upon admission and its outcomes in patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Adel Hamed Elbaih

    2017-01-01

    Full Text Available Background: Coronary heart disease (CHD is the main leading cause of morbidity and mortality in patients with diabetes mellitus. Hyperglycemia on admission was associated with a worse outcome for all patients admitted with ACS. Aim: To correlate the relationship between hyperglycemia with acute coronary syndrome and poor outcome. Methodology: Clinical evaluation of the patients were carried out on arrival to Emergency Department regarding: Initial assessment of patient general condition either stable or not through; ABCDE (air way and cervical spine control, breathing, circulation, neurological dysfunction and exposure. Then determine the characters and types of chest pain. Assess the condition of the patients either stable or unstable which will determine the needed investigations and plane of management. Results: the mortality was higher in patients with RBG more than 300 mg/dl (68.4 %, (10.5 % of the patients had ranged from 250 ─ < 300 mg/dl, and the patients had ranged from 200 ─ < 250 mg/dl were (10.5 %. The patients had ranged from 160 ─ < 200 mg/dl were (5.3 and there were (5.3 of the patients had ranged from 70 ─ < 160mg/dl. Conclusions: The data from this study have shown that hyperglycemia on admission was associated with a worse outcome for all patients admitted with ACS.

  8. The study of the prognostic value scales of assessing the risk of adverse coronary events in patients with acute coronary syndrome without ST-segment elevation in combination with comorbid conditions

    Directory of Open Access Journals (Sweden)

    Dorokhova O.V.

    2014-12-01

    Full Text Available Objective: to identify the most prognostically significant scale risk assessment of patients with acute coronary syndrome without ST-segment elevation in combination with diabetes mellitus type 2, chronic renal failure, multifo-cal coronarocardiosclerosis, dyscirculatory encephalopathy. Material and methods. 260 patients with acute coronary syndrome without ST-segment elevation were divided into 4 groups according to the presence of severe concomitant diseases: patients with diabetes mellitus type 2 (71 people, chronic renal failure (49, multifocal lesions of the coronary arteries (76 and patients with dyscirculatory encephalopathy of grade 2-3, including ischemic stroke (64. All patients were stratified by major scales risk: TIMI, GRACE, PURSUIT. The development of negative coronary events was assessed in hospital and during the year after discharge. On the basis of the results, all scales were studied using the criterion of Mann-Whitney and identified the most predictably significant groups of patients with specific comorbid conditions. Results. It is revealed that the significance of the scales TIMI and GRACE in the study of distant forecast (up to 6 months is the most reliable with acute coronary syndrome without ST-segment elevation in combination with diabetes mellitus type 2. For the patients with combination with chronic renal insufficiency the best prognostic significance was obtained by the GRACE scale in the study of hospital risk and forecast up to 6 months. TIMI and GRACE scales in the study of hospital risk and forecast up to 6 months had the greatest prognostic significance for the patients with acute coronary syndrome without ST-segment elevation on the background of multifocal lesions of the coronary arteries. For the patients with dyscirculatory encephalopathy of the 2nd and 3rd grades, the greatest prognostic significance was obtained by stratification of risk on PURSUIT and GRACE scales in the study of hospital risk and

  9. Value of electroneurography as a prognostic indicator for recovery in acute severe inflammatory facial paralysis: a prospective study of Bell's palsy and Ramsay Hunt syndrome.

    Science.gov (United States)

    Byun, Hayoung; Cho, Yang-Sun; Jang, Jeon Yeob; Chung, Kyu Whan; Hwang, Soojin; Chung, Won-Ho; Hong, Sung Hwa

    2013-10-01

    To evaluate the prognostic and predictive value of electroneuronography (ENoG) in acute severe inflammatory facial paralysis, including Bell's palsy and Ramsay Hunt syndrome (RHS). Prospective observational study. Patients with acute severe facial paralysis of House-Brackmann (H-B) grade IV or worse and diagnosed with Bell's palsy or RHS were enrolled from August 2007 to July 2011. After treatment with oral corticosteroid, antiviral agent, and protective eye care, patients were followed up until recovery or 12 months from onset. Sixty-six patients with Bell's palsy and 22 with RHS were included. Multiple logistic regression analysis showed significant effect of ENoG value on recovery in both Bell's palsy and RHS. Values of ENoG were significantly worse in RHS than Bell's palsy. Chance of early recovery within 6 weeks after correction of ENoG effect was still significantly worse in RHS. Logistic regression analysis showed 90% chance of recovery within 6 months, expected with ENoG values of 69.2% degeneration (Bell's palsy) and 59.3% (RHS). The receiver operating characteristics (ROC) curves showed ENoG values of 82.5% (Bell's palsy) and 78.0% (RHS) as a critical cutoff value of nonrecovery until 1 year, with the best sensitivity and specificity. A higher chance of recovery was expected with better ENoG in Bell's palsy and RHS. Based on our data, nonrecovery is predicted in patients with ENoG value greater than 82.5% in Bell's palsy, and 78% in RHS. 4. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Prognostic significance of mitral regurgitation in long-term all-cause mortality in patients aged ≥ 80 years with acute coronary syndrome.

    Science.gov (United States)

    Li, Shijun; Barywani, Salim; Fu, Michael

    2014-09-20

    Mitral regurgitation (MR) has been shown to be associated with a poor prognosis in the patients with acute myocardial infarction, whether or not percutaneous coronary intervention (PCI) is employed. However, the long-term prognostic significance of MR in octogenarian patients with acute coronary syndrome (ACS) remains unknown. We sought to determine the impact of MR on long-term all-cause mortality and to further reveal whether PCI could influence the prognosis in octogenarian MR patients with ACS. In this study, we included a total of 353 consecutive hospitalized patients, aged ≥ 80 years, with ACS during the period of 5-year follow-up. Association between MR and long-term all-cause mortality was analyzed both in a overall cohort and in a matched cohort developed from a propensity score analysis. MR was independently associated with long-term all-cause mortality in the overall and matched cohorts (hazard ratio (HR) 1.58, 95% CI 1.01-2.47, P=0.043; HR 1.90, 95% CI 1.15-3.13, P=0.013). In the subgroup treated with PCI, MR also exhibited higher long-term all-cause mortality, PCI remained an independent determinant of improving long-term survival rate by reducing the mortality by 15.1% in ACS patients with MR aged ≥ 80 years. Our study demonstrates that MR is independently associated with long-term all-cause mortality, and PCI is an independent determinant for improving the long-term survival rate in the octogenarian ACS patients with MR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. [Re-evaluation of classification of myelodysplastic syndromes with low percentage bone marrow blasts].

    Science.gov (United States)

    Yu, Ming-Hua; Xu, Ze-Feng; Li, Lin; Nie, Ling; Liu, Liang; Zhang, Yue; Qin, Tie-Jun; Hao, Yu-Shu; Xiao, Zhi-Jian

    2009-01-01

    To apply the WHO criteria and the minimal diagnostic criteria to the classification of myelodysplastic syndromes (MDS) with low percentage (MDS patients with less than 0.050 BM blasts diagnosed between 1988 and 2005 according to FAB criteria were retrospectively reclassified with WHO criteria (2001) and minimal diagnostic criteria. According to the WHO criteria, 5 patients were diagnosed as refractory anemia (RA), 7 as refractory anemia with ringed sideroblasts (RARS), 76 as refractory cytopenia with multilineage dysplasia (RCMD), 9 as RCMD-RS, 35 as MDS-unclassified (MDS-U), 3 as 5q - syndromes, and the rest 75 patients could not be classified suitably. Among the latter 75 patients 16 BM smears showed dysplasia in more than 2 cell lineage but only unilineage cytopenia in peripheral blood (PB). Nine of them were reclassified as RCMD after followed up for more than half a year. Forty-four BM smears showed erythroid dysplasia only, but bicytopenia or pancytopenia in PB. Twenty-seven of them were classified as RCMD after follow-up. Fifteen BM smears not showed dysplasia in any myeloid lineage were reclassified as MDS (5 patients), HS-MDS (5 patients) and idiopathic cytopenia of uncertain significance (ICUS) (5 patients) according to the MDS minimal diagnostic criteria. According to WHO criteria (2001), RA is the least diagnosis in MDS. The minimal diagnostic criteria for MDS classification of patients not fulfilled the standard criteria of MDS.

  12. WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.

    Science.gov (United States)

    Brayer, Jason; Lancet, Jeffrey E; Powers, John; List, Alan; Balducci, Lodovico; Komrokji, Rami; Pinilla-Ibarz, Javier

    2015-07-01

    Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms' Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity. Six vaccinations were delivered biweekly, continuing then monthly until patients received 12 vaccinations or showed disease relapse or progression. Therapeutic efficacy was evaluated by progression-free and overall survival. Immune responses were evaluated by delayed-type hypersensitivity testing and T-cell IFNγ ELISPOT at specified intervals. In 16 patients who received at least one vaccination, 10 completed the planned course of six vaccinations and six continued for up to six additional monthly vaccinations. Vaccinations were well tolerated, with no patients discontinuing due to toxicity. One of two patients with high-risk MDS experienced a prolonged decrease in transfusion dependence. Two of 14 AML patients demonstrated relapse-free survival >1 year. Both patients were in CR2 at time of vaccination, with duration of their remission exceeding duration of their first remission, suggesting a potential benefit. Our WT1 vaccine was well-tolerated. The clinical benefit that we observed in several patients suggests engagement of a protective immune response, indicating a need for further trials. © 2015 Wiley Periodicals, Inc.

  13. Prognostic Factors Affecting Union After Ulnar Shortening Osteotomy in Ulnar Impaction Syndrome: A Retrospective Case-Control Study.

    Science.gov (United States)

    Cha, Soo Min; Shin, Hyun Dae; Ahn, Ki Jun

    2017-04-19

    Ulnar shortening osteotomy (USO) is a widely adopted procedure with excellent outcomes. However, delayed union or nonunion has occasionally been observed. The purpose of this retrospective case-control study was to identify variables affecting osseous consolidation after USO in patients with ulnar impaction syndrome. The study included 325 patients who had undergone USO between March 2008 and March 2014. We evaluated the association between union and basic demographic factors as well as preoperative pain (assessed on a visual analog scale [VAS]), range of wrist motion, grip strength, and modified Mayo wrist score. We also assessed the association of union with radiographic variables such as the degree of dorsal subluxation of the ulna, preoperative and postoperative ulnar variance, morphological type of the distal radioulnar joint, gap at the osteotomy site, and presence of newly developed arthritic changes during the follow-up period. Finally, variables associated with operative conditions, such as degeneration of the triangular fibrocartilage complex, use of a parallel double-blade saw, type of plate used for fixation, number of screws, and plate position on the volar or dorsal ulnar surface were investigated. Ulnar union was achieved in 294 patients (group 1), and 31 patients had delayed union or nonunion (group 2). On univariate and multivariate analyses, smoking, low bone mineral density (BMD), a decreased range of motion of the wrist, and use of a double-blade saw were found to be significant factors for an adverse radiographic outcome (nonunion or delayed union). Delayed union or nonunion occurred in about 10% of patients treated with USO. We suggest that it may be preferable to perform USO in nonsmokers, patients with normal bone density, and those without restricted wrist motion. Also, we recommend the use of a single-blade saw when performing the osteotomy. Therapeutic Level III. See Instructions for Authors for a complete description of levels of

  14. SETBP1 mutations as a biomarker for myelodysplasia /myeloproliferative neoplasm overlap syndrome

    OpenAIRE

    Linder, Katherine; Iragavarapu, Chaitanya; Liu, Delong

    2017-01-01

    Myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndrome has been described since the 2001 WHO classification as disorders that have both proliferative and dysplastic changes simultaneously. Specific disorders include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL negative atypical chronic myeloid leukemia (aCML) and unclassifiable MDS/MPN (MPN/MDS-U). Recurrent gene mutations in these conditions have been described. Among them, SETBP1...

  15. The Mice Drawer System Tissue Sharing Program (MDS-TSP)

    Science.gov (United States)

    Biticchi, Roberta; Cancedda, Ranieri; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Ruggiu, Alessandra; Tasso, Roberta; Tavella, Sara

    Several organs and apparatus are affected by weightless conditions and in particular by the weightless experienced during space flights. Therefore space missions are good opportunities to investigate in a whole organism the controlling cellular and molecular mechanisms. For this type of studies mice represent an excellent animal model for several reasons: reduced body size, relatively short time needed to reach adulthood, availability of strains with different genetic background and of different transgenic lines, etc. In line with the International Space Station (ISS) development, the Italian Space Agency (ASI) contracted Thales Alenia Space Italia, the largest Italian aerospace industry, to design and build a spaceflight payload for rodent research on ISS, the Mouse Drawer System (MDS -see abstract P. Cipparelli et al.). This payload meets NIH guideline for several physical parameters to maintain 6 animals in good health conditions in a space environment. Given the interest of our laboratory in the microgravity induced skeleton alterations, we focused our attention on transgenic mice over-expressing pleiotrophin (PTN) under the control of the human bone specific osteocalcin promoter. This protein is a heparin-binding cytokine with different functions. PTN is expressed by the cells in an early differentiation stage and is upregulated in tissue injury and wound repair. PTN is specifically involved in bone formation, neurite outgrowth and angiogenesis. As PTN-transgenic mice show an increased bone mass and mineralization, we decided to use this mouse model in the flight experiment and to study its potential role in counteracting bone loss in microgravity. Not all mouse strains are equally suitable for flight. After preliminary tests in the MDS breadboard at our animal facility on the behavior of different mouse strains, PTN-transgenic mice originally obtained in the BDF strain were backcrossed in the C57Bl/J10 strain before being used in this study. In order to

  16. Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of ≥120 g/L with darbepoetin alfa ± filgrastim or erythrocyte transfusions

    DEFF Research Database (Denmark)

    Nilsson-Ehle, Herman; Birgegård, Gunnar; Samuelsson, Jan

    2011-01-01

    Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels...... has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L....

  17. Impact of chromosome alterations, genetic mutations and clonal hematopoiesis of indeterminate potential (CHIP) on the classification and risk stratification of MDS.

    Science.gov (United States)

    Ganguly, Bani Bandana; Banerjee, Debasis; Agarwal, Mohan B

    2018-03-01

    The advent of technological development has undoubtedly advanced biological and molecular inputs for better understanding the heterogeneous hematopoietic pre-malignant disorder of the stem cells known as myelodysplastic syndromes (MDS). Chromosomal rearrangements, including del(3q/5q/7q/11q/12p/20q), loss of 5/7/Y, trisomy 8/19, i(17q), etc. frequently detected in MDS with variable frequencies and combinations, are the integral components of the 5-tier risk-stratification and WHO-2016 classification. Observations on mutations in genes involved in RNA-splicing, DNA methylation, chromatin modification, transcription factor, signal transduction/kinases, RAS pathway, cohesin complex, DNA repair and other pathways have given insights in independent effects and biological interaction of co-occurrence on disease-phenotype and treatment outcome. However, recent concepts of clonal hematopoiesis of indeterminate potential (CHIP) and idiopathic cytopenia of undetermined significance (ICUS) have urged a re-definition of mutational events in non-clonal cytopenia and non-MDS healthy elderly but with a higher risk of overt leukemia. Considering gene mutations, chromosomal alterations, CHIP, ICUS and their significance in classification and risk-scoring certainly presents a comprehensive picture of disease-phenotype towards better understanding of MDS-pathogenesis, its evolution to AML and its response to therapeutic agents. The present review summarizes chromosomal and gene mutations, co-existence of mutational complexity, and WHO-2016 classification and risk-stratifications of MDS to facilitate a better understanding of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Age-related changes of healthy bone marrow cell signaling in response to growth factors provide insight into low risk MDS.

    Science.gov (United States)

    Kornblau, Steven M; Cohen, Aileen C; Soper, David; Huang, Ying-Wen; Cesano, Alessandra

    2014-11-01

    Single Cell Network Profiling (SCNP) is a multiparametric flow cytometry-based assay that quantifiably and simultaneously measures changes in intracellular signaling proteins in response to in vitro extracellular modulators at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder of hematopoietic stem cells that occurs in elderly subjects and is characterized by dysplasia and ineffective hematopoiesis. The functional responsiveness of MDS bone marrow (BM) hematopoietic cells, including functionally distinct myeloid and erythroid precursor subsets, to hematopoietic growth factors (HGF) and the relationship of modulated signaling to disease characteristics is poorly understood. SCNP was used first to examine the effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34 expressing cell subsets in healthy BM (n = 15). SCNP was then used to map functional signaling profiles in low risk (LR) MDS (n = 7) for comparison to signaling in samples from healthy donors and to probe signaling associations within clinically defined subgroups. In healthy BM samples, signaling responses to HGF were quite homogeneous (i.e., tightly regulated) with age-dependent effects observed in response to EPO but not to GCSF. Despite the relatively small number of samples assayed in the study, LR MDS could be classified into distinct subgroups based on both cell subset frequency and signaling profiles. As a correlate of underlying genetic abnormalities, signal transduction analyses may provide a functional and potentially clinically relevant classification of MDS. Further evaluation in a larger cohort is warranted. © 2013 Clinical Cytometry Society.

  19. Autoimmune diseases and myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. © 2016 Wiley Periodicals, Inc.

  20. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Udit Bhaskar Bhatnagar

    2016-01-01

    Full Text Available Therapy related acute myelogenous leukemia (AML and myelodysplastic syndromes (MDS have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies.

  1. Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study

    Directory of Open Access Journals (Sweden)

    Fries Brant E

    2005-01-01

    Full Text Available Abstract Background The objective of this study was to examine the Minimum Data Set (MDS and Geriatric Depression Scale (GDS as measures of depression among nursing home residents. Methods The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version. Demographic, psychiatric, and cognitive data were obtained using the MDS. Level of depression was operationalized as: (1 a sum of the MDS Depression items; (2 the MDS Depression Rating Scale; (3 the 15-item GDS; and (4 the five-item GDS. We compared missing data, floor effects, means, internal consistency reliability, scale score correlation, and ability to identify residents with conspicuous depression (chart diagnosis or use of antidepressant across cognitive impairment strata. Results The GDS and MDS Depression scales were uncorrelated. Nevertheless, both MDS and GDS measures demonstrated adequate internal consistency reliability. The MDS suggested greater depression among those with cognitive impairment, whereas the GDS suggested a more severe depression among those with better cognitive functioning. The GDS was limited by missing data; the DRS by a larger floor effect. The DRS was more strongly correlated with conspicuous depression, but only among those with cognitive impairment. Conclusions The MDS Depression items and GDS identify different elements of depression. This may be due to differences in the manifest symptom content and/or the self-report nature of the GDS versus the observer-rated MDS. Our findings suggest that the GDS and the MDS are not interchangeable measures of depression.

  2. Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study

    Science.gov (United States)

    Koehler, Melissa; Rabinowitz, Terry; Hirdes, John; Stones, Michael; Carpenter, G Iain; Fries, Brant E; Morris, John N; Jones, Richard N

    2005-01-01

    Background The objective of this study was to examine the Minimum Data Set (MDS) and Geriatric Depression Scale (GDS) as measures of depression among nursing home residents. Methods The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version. Demographic, psychiatric, and cognitive data were obtained using the MDS. Level of depression was operationalized as: (1) a sum of the MDS Depression items; (2) the MDS Depression Rating Scale; (3) the 15-item GDS; and (4) the five-item GDS. We compared missing data, floor effects, means, internal consistency reliability, scale score correlation, and ability to identify residents with conspicuous depression (chart diagnosis or use of antidepressant) across cognitive impairment strata. Results The GDS and MDS Depression scales were uncorrelated. Nevertheless, both MDS and GDS measures demonstrated adequate internal consistency reliability. The MDS suggested greater depression among those with cognitive impairment, whereas the GDS suggested a more severe depression among those with better cognitive functioning. The GDS was limited by missing data; the DRS by a larger floor effect. The DRS was more strongly correlated with conspicuous depression, but only among those with cognitive impairment. Conclusions The MDS Depression items and GDS identify different elements of depression. This may be due to differences in the manifest symptom content and/or the self-report nature of the GDS versus the observer-rated MDS. Our findings suggest that the GDS and the MDS are not interchangeable measures of depression. PMID:15627403

  3. [Analysis of prognostic risk factors in the patients with acute exacerbation of chronic cor pulmonale and obstructive sleep apnea-hypopnea syndrome in high altitude area].

    Science.gov (United States)

    Yang, Sheng-yue; Luo, Xiao-hong; Feng, En-zhi; Qi, Yu-shu; Liu, Rui-nian; Yin, He; Zhang, Ai-jun; Zhao, Li-hong

    2010-05-01

    To assess the prognostic risk factors in the patients with acute exacerbation of chronic cor pulmonale (AEHACCP) and obstructive sleep apnea-hypopnea syndrome (OSAHS) in high altitude area. The relations between neck circumference (Nc), body mass index (BMI), arterial blood gases, polysomnography (PSG) parameters and prognosis from 66 patients with AEHACCP and OSAHS (31 survivors, 35 non-survivors) were studied by one variable analysis and multivariable Logistic regression analysis. The results of one variable analysis showed that in patients with AEHACCP and OSAHS, Nc> or =45 cm, BMI > or =28 kg/m(2) , arterial oxygen partial pressure (PaO(2)) or =45 mm Hg, apnea-hypopnea index (AHI)> or = 40 times/h, sleep mean arterial oxygen saturation (MSaO(2)) or =50% and difference between basic and minimum SaO(2) during sleep(Delta SaO(2))> or = 0.20 were closely correlated with prognosis. The Logistic regression models showed that Nc> or =45 cm [odds ratio (OR)=6.781, 95% confidence interval (95%CI)=1.153-17.502, P=0.007], BMI> or =28 kg/m(2) (OR=7.562, 95%CI=1.012-23.457, P=0.004), mPAP> or =45 mm Hg (OR=6.991, 95%CI=1.353-20.155, P=0.003), AHI> or =40 times/h (OR=7.258, 95%CI=1.526-18.022, P=0.006), MSaO(2) or =50% (OR=5.593, 95%CI=1.265-21.589, P=0.008) and Delta SaO(2)> or =0.20 (OR=6.551, 95%CI=1.495-18.920, P=0.007) were independent significant risk factors in prognosis of patients with AEHACCP and OSAHS. The patients with AEHACCP and OSAHS, Nc> or =45 cm, BMI> or =28 kg/m(2), mPAP> or =45 mm Hg, AHI> or = 40 times/h, MSaO(2) or =50% and Delta SaO(2)> or =0.20 are risk factors leading to a rise in mortality. It is important to use these parameters to guide clinical therapy, and to judge the prognosis so as to reduce the mortality of patients with AEHACCP and OSAHS by monitoring the above risk factors in clinical practice.

  4. Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Prachi Jain

    2017-01-01

    Full Text Available Patients with high risk myelodysplastic syndromes (MDS and acute myelogenous leukemia (AML are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

  5. Stem cell transplantation for leukemias following myelodysplastic syndromes or secondary to cytotoxic therapy.

    NARCIS (Netherlands)

    Witte, T.J.M. de; Oosterveld, M.; Span, L.F.R.; Muus, P.; Schattenberg, A.V.M.B.

    2002-01-01

    Two main forms of therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) have been recognized. The most frequent type, occurring after treatment with alkylating agents, is characterized by abnormalities of chromosomes 5 and/or 7 and t-MDS/AML following treatment with

  6. Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

    Directory of Open Access Journals (Sweden)

    F.G.J. Calkoen

    2015-03-01

    An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.

  7. TOPICS-MDS: Veelzijdige bron voor wetenschappelijke en maatschappelijke kennisgeneratie ten behoeve van de ouderenzorg

    NARCIS (Netherlands)

    van den Brink, D.; Lutomski, J.E.; Qin, L.; den Elzen, W.P.J.; Kempen, G.I.J.M.; Krabbe, P.F.M.; Steyerberg, E.W.; Muntinga, M.E.; Moll van Charante, E.P.; Bleijenberg, N.; Olde Rikkert, M.G.M.; Melis, R.J.F.

    2015-01-01

    Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a

  8. Minimal clinically important difference on the Motor Examination part of MDS-UPDRS.

    Science.gov (United States)

    Horváth, Krisztina; Aschermann, Zsuzsanna; Ács, Péter; Deli, Gabriella; Janszky, József; Komoly, Sámuel; Balázs, Éva; Takács, Katalin; Karádi, Kázmér; Kovács, Norbert

    2015-12-01

    Recent studies increasingly utilize the Movement Disorders Society Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS). However, the minimal clinically important difference (MCID) has not been fully established for MDS-UPDRS yet. To assess the MCID thresholds for MDS-UPDRS Motor Examination (Part III). 728 paired investigations of 260 patients were included. At each visit both MDS-UPDRS and Clinician-reported Global Impression-Improvement (CGI-I) scales were assessed. MDS-UPDRS Motor Examination (ME) score changes associated with CGI-I score 4 (no change) were compared with MDS-UPDRS ME score changes associated with CGI-I score 3 (minimal improvement) and CGI-I score 5 (minimal worsening). Both anchor- and distribution-based techniques were utilized to determine the magnitude of MCID. The MCID estimates for MDS-UPDRS ME were asymmetric: -3.25 points for detecting minimal, but clinically pertinent, improvement and 4.63 points for observing minimal, but clinically pertinent, worsening. MCID is the smallest change of scores that are clinically meaningful to patients. These MCID estimates may allow the judgement of a numeric change in MDS-UPDRS ME on its clinical importance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. New q-ary quantum MDS codes with distances bigger than q/2

    Science.gov (United States)

    He, Xianmang; Xu, Liqing; Chen, Hao

    2016-07-01

    The construction of quantum MDS codes has been studied by many authors. We refer to the table in page 1482 of (IEEE Trans Inf Theory 61(3):1474-1484, 2015) for known constructions. However, there have been constructed only a few q-ary quantum MDS [[n,n-2d+2,d

  10. Aircraft Anomaly Prognostics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Ridgetop Group will leverage its proven Electromechanical Actuator (EMA) prognostics methodology to develop an advanced model-based actuator prognostic reasoner...

  11. Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy

    NARCIS (Netherlands)

    Damman, Peter; Kempf, Tibor; Windhausen, Fons; van Straalen, Jan P.; Guba-Quint, Anja; Fischer, Johan; Tijssen, Jan G. P.; Wollert, Kai C.; de Winter, Robbert J.; Hirsch, Alexander

    2014-01-01

    No five-year long-term follow-up data is available regarding the prognostic value of GDF-15. Our aim is to evaluate the long-term prognostic value of admission growth-differentiation factor 15 (GDF-15) regarding death or myocardial infarction (MI) in patients with non-ST-elevation acute coronary

  12. Two cases of therapy-related myelodysplastic syndrome after concurrent oral cancer chemoradiotherapy

    International Nuclear Information System (INIS)

    Doi, Katsuyuki; Asano, Takanori; Kinoshita, Takashi

    2010-01-01

    Therapy-related myelodysplastic syndrome (t-MDS) and therapy-related leukemia (TRL) are reported increasingly often, and we report two cases of T-MDS after concurrent chemoradiotherapy (CCRT) with oral cancer. Patients underwent CCRT with cisplatin (CDDP) or carboplatin (CBDCA). The interval between primary CCRT and t-MDS was 11 months in 1 case and 14 years in the other. Chromosomal analysis indicated abnormal karyotypes. Platinum has a relatively lower t-MDS risk than alkylating agents or topoisomerase II inhibitors, but our experience supports concurrent use of radiotherapy with platinum affects the risk of t-MDS. If pancytopenia is detected after CCRT, bone marrow and cytogenetic examinations should be conducted to rule out t-MDS. (author)

  13. [Correlation of chromosome karyotype with dyshaematopoiesis and reticulin in myelodysplastic syndrome].

    Science.gov (United States)

    Cheng, Yan-Chao; Sun, Hui; Gan, Si-Lin; Liu, Yan-Fang; Xie, Xin-Sheng; Zhang, Qiu-Tang; Li, Tao; Gao, Juan

    2013-04-01

    This study was purposed to explore the correlation of chromosome karyotype with dyshaematopoiesis and reticulin in myelodysplastic syndrome (MDS). The data of 202 MDS patients diagnosed and treated in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in term of chromosome karyotype, dyshaematopoiesis and reticulin detection results. The chromosome karyotypes were categorized according to the International Prognostic Scoring System (IPSS). The results showed that there was a positive correlation between chromosome karyotype grading and number of lineages with dyshaematopoiesis (r = 0.443, P karyotypes were 44.4%, 71.4% and 96.3% respectively. There was a positive correlation between chromosome karyotype grading and reticulin grading (r = 0.451, P karyotypes were 36.8%, 64.3% and 92.6% respectively. The detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, the positive rate of reticulin and reticulin grade in patients with poor karyotypes were higher than those in patients with intermediate or good chromosome karyotypes (separately P karyotypes were higher than those in patients with good chromosome karyotypes (separately P karyotype grading positively correlates with the number of lineages with dyshaematopoiesis and reticulin grading. When the chromosome karyotype changed from good to poor, the detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, positive rate of reticulin and reticulin grading became higher and higher.

  14. [VALIDATION OF THE HUNGARIAN MDS-UPDRS: WHY DO WE NEED A NEW PARKINSON SCALE?].

    Science.gov (United States)

    Horvath, Krisztina; Aschermann Zsuzsanna; Acs, Péter; Bosnyák, Edit; Deli, Gabriella; Pál, Endre; Késmárki, Ildikó; Horváth Réka; Takács, Katalin; Komoly, Sámuel; Bokor, Magdolna; Rigó, Eszter; Lajtos, Júlia; Klivényi, Péter; Dibó, György; Vécsei, László; Takáts, Annamária; Tóth, Adrián; Imre, Piroska; Nagy, Ferenc; Herceg, Mihály; Hidasi, Eszter; Kovács, Norbert

    2014-03-30

    The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been published in 2008 as the successor of the original UPDRS. The MDS-UPDRS organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new MDS-UPDRS and its validation process into Hungarian. Two independent groups of neurologists translated the text of the MDS-UPDRS into Hungarian and subsequently back-translated into English. After the review of the back-translated English version by the MDS-UPDRS translation administration team, cognitive pretesting was conducted with ten patients. Based on the results of the initial cognitive pretesting, another round was conducted. For the large field testing phase, the Hungarian official working draft version of MDS-UPDRS was tested with 357 patients with Parkinson's disease (PD). Confirmatory factor analyses (CFA) determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the English-language version. For all four parts of the Hungarian MDS-UPDRS, the CFI was ≥ 0.94. The overall factor structure of the Hungarian version was consistent with that of the English version based on the high CFIs for all the four parts of the MDS-UPDRS in the CFA; therefore, this version was designated as the "OFFICIAL GUNGARIAN VERSION OF THE MDS-UPDRS'.

  15. [Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment].

    Science.gov (United States)

    Cheng, Huan-Chen; Liu, Sheng-Wei; Liu, Yu; Zhao, Xue-Fei; Li, Wei; Qiu, Lin; Ma, Jun

    2017-12-01

    To detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. The specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. TET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. Both AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.

  16. Etiological factors of myelo-dysplastic syndromes; Facteurs etiologiques des syndromes myelodysplasiques

    Energy Technology Data Exchange (ETDEWEB)

    Nisse, C. [Centre Hospitalier Universitaire, 59 - Lille (France)

    1997-09-01

    Specific epidemiologic data on myelo-dysplastic syndromes are rare. Analysis of data is in fact affected by problems of terminology and classification. The link between the exposure to ionizing radiation or alkylating agents and MDS is well established. Etiologic factors of acute leukemia, or new factors such as non ionizing radiation, solvent, ethylene oxide, glycol ethers, tobacco smoke, exhaust gases, agricultural work have been hypothesized but should be confirmed by other studies on MDS. (author)

  17. Uncoding the genetic heterogeneity of myelodysplastic syndrome.

    Science.gov (United States)

    Lindsley, R Coleman

    2017-12-08

    Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The type and severity of hematopoietic dysfunction in MDS are highly variable, and the kinetics of disease progression are difficult to predict. Genomic studies have shown that MDS is typically driven by a multistep somatic genetic process affecting a core set of genes. By definition, recurrent MDS driver mutations all drive clonal dominance, although they can have stereotyped positions in the clonal hierarchy or patterns of comutation association and exclusivity. Furthermore, environmental context, such as exposures to cytotoxic chemotherapy or the presence of germ-line predisposition, can influence disease pathogenesis and clinical outcomes. This review will address how an enhanced understanding of MDS genetics may enable refinement of current diagnostic schema, improve understanding of the pathogenesis of therapy-related MDS, and identify germ-line predispositions to development of MDS that are more common than recognized by standard clinical evaluation. © 2016 by The American Society of Hematology. All rights reserved.

  18. Corticosteroid-responsive nephrotic syndrome in children with myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Bogdanović Radovan

    2002-01-01

    Full Text Available Several reports have documented various forms of glomerular diseases in adults with myelodysplastic syndromes (MDS, but similar reports in children are lacking. We describe two children with MDS-associated with steroid-responsive nephrotic syndrome (NS. Patient 1, who had MDS with myelofibrosis, presented also hepatosplenomegaly, pancytopenia, chronic hepatitis, moderate proteinuria, hypocomplementemia and elevated ANA titer. During initial prednisone treatment proteinuria markedly diminished and partial but transient haematological improvement occurred. Relapse subsequently occurred that was manifested by overt NS and pancytopenia. High doses of prednisolone led to remission of the renal disease but haematological remission did not occur. Persisting pancytopenia and repeated infections terminated in sepsis, two years after the onset of MDS. Patient 2, who had refractory anemia with clonal monosomy 19, manifested bowel disease, hepatospleno- megaly, anaemia and non-organic specific autoantibodies. Prednisone led to both clinical and haematological remission. Haematologic disease relapsed 12 months later, when nephrotic-range proteinuria, haematuria and mild azotaemia were also found. Corticosteroid treatment led to long-lasting renal and haematologic remission, maintained by a small dosage of prednisone. In both patients renal biopsy findings were consistent with those seen in idiopathic NS. A Medline search disclosed 16 cases of glomerulopathy in the course of MDS in adult patients. Clinical features included NS, usually accompanied by renal insufficiency with either acute, chronic, or rapidly progressive glomerulonephritis. On biopsy, membranous nephropathy, crescentic or mesangial proliferative glomerulonephritis and AL amyloidosis, were found. We conclude: (1 that glomerular disease may be present and should be searched for in patients with MDS; (2 that MDS can be added to the list of rare conditions associated with corticosteroid

  19. [Prognostic factors in patients with non-ST-segment elevation acute coronary syndrome concurrent with type 2 diabetes mellitus (according to the results of the registry)].

    Science.gov (United States)

    Golikov, A P; Berns, S A; Stryuk, R I; Shmidt, E A; Golikova, A A; Barbarash, O L

    To investigate factors that influence annual prognosis in patients with non-ST-segment elevation acute coronary syndrome ((NSTEACS) concurrent with type 2 diabetes mellitus (DM2). The registry of patients with NSTEACS (non-ST-segment elevation myocardial infarction (NSTEMI), unstable angina) included 415 patients, of them 335 had no carbohydrate metabolic disorders, 80 had DM2. The follow-up period, during which the prognosis was evaluated in the patients, was one year after hospital discharge following the index NSTEACS event. Lipidogram readings and the serum levels of endothelin-1 (ET-1), sP-selectin, sE-selectin, and sPECAM were determined on day 10 after admission to hospital. All the patients underwent coronary angiography (CA), Doppler ultrasound of peripheral arteries during their hospital stay. The patients with DM2 versus those without diabetes proved to be significantly older and to have a higher body mass index; among them there were more women, they were noted to have more frequently hypertension and less frequently smoked. The presence of DM2 was associated with significantly increased intima-media thickness and higher GRACE scores (p=0.013) as compared to those in the patients with normal carbohydrate metabolism. There were significant differences in high-density lipoprotein levels that were lower, as well as in triglyceride levels and atherogenic index, which were higher in patients with DM2 than in those without this condition. In addition, there were significant differences in ET-1, sP-selectin, sE-selectin, and sPECAM levels that were significantly higher in the DM2 group. Moreover, the levels of ET-1 and sPECAM were above normal in both the DM and non-DM2 groups. Assessment of poor outcomes at one year of the observation established that cardiovascular mortality rates were significantly higher and coronary angiography was performed much less frequently in the DM2 group. The most significant prognostic factors associated with a poor prognosis

  20. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT.

    Science.gov (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M

    2015-04-01

    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  1. MDS-Multifunctional Dynamometer for Application in Space

    Science.gov (United States)

    Adamcik, G.; Barta, N.; Talla, R.; Angeli, T.; Kozlovskaya, I. B.; Grigoriev, A. I.; Tschan, H.; Bachl, N.

    2008-06-01

    The project MDS (Multifunctional Dynamometer for Application in Space) is an international collaboration of the University of Vienna (Faculty of Sport Science, Department of Sport and Exercise Physiology), the Russian Academy of Sciences (Institute of Biomedical Problems) and the Technical University of Vienna (Institute for Engineering Design and Logistics Engineering) with the aim to develop a training and diagnostic device that counteracts the muscle and bone loss during long term space flights. Due to the scientific results of the last years research in space medicine, it is well known, that the muscles and bones of the lower extremities and the trunk are most affected by the atrophy. Based on this knowledge a various number of resistance exercises can be done in order to train the muscles of these parts of the body and to increase the efficiency of the training by intra- and intermuscular coordination. The resisting power for the training is provided by an electric motor, thereby force, position and speed of the training can be well-regulated for different training modes.

  2. Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

    Science.gov (United States)

    Correa-Fernandez, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

    2012-01-01

    Objective: Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method: Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple…

  3. MDS 3.0 for Nursing Homes and Swing Bed Providers

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MDS is a powerful tool for implementing standardized assessment and for facilitating care management in nursing homes (NHs) and non-critical access hospital...

  4. Magnetic Decreases (MDs and mirror modes: two different plasma β changing mechanisms

    Directory of Open Access Journals (Sweden)

    E. Echer

    2010-09-01

    Full Text Available We discuss two different physical processes that create localized high β plasma regions. One is nonlinear wave-steepening, generating magnetic decreases (MDs by a ponderomotive force. The other is the mirror instability generating alternating high and low β plasma regions. It is demonstrated that MDs and mirror modes are observationally quite different structures. MDs spatially occur in interplanetary space and mirror modes primarily in planetary magnetosheaths. MDs are characterized by: 1 variable (exponentially decreasing number with increasing angular changes, 2 variable (exponentially decreasing thicknesses, and 3 no characteristic inter-event spacings. In sharp contrast, mirror modes are characterized by: 1 little or no angular changes across the structures, 2 a characteristic scale size, and 3 are quasiperiodic in nature. Arguments are presented for the recently observed magnetic dips in the heliosheath being mirror mode structures. The sources of free energy for instability are discussed. Both structures are important for energetic particle transport in astrophysical and heliospheric plasmas.

  5. Study of Rpl22 in MDS and AML

    Science.gov (United States)

    2015-10-01

    depleting cells expressing lineage markers (Fig.4). We also analyzed the phenotype in Rpl22-/-p53-/- mice and found the mice exhibit similar phenotype...prognostic marker in AML. On the other hand, because we found Like1 is induced upon Rpl22 inactivation and its expression is required and sufficient...Ferreira AM, et al. (2014) High frequency of RPL22 mutations in microsatellite -unstable colorectal and endometrial tumors. Hum Mutat 35(12):1442-1445. 9

  6. Minimum variance and variance of outgoing quality limit MDS-1(c1, c2) plans

    Science.gov (United States)

    Raju, C.; Vidya, R.

    2016-06-01

    In this article, the outgoing quality (OQ) and total inspection (TI) of multiple deferred state sampling plans MDS-1(c1,c2) are studied. It is assumed that the inspection is rejection rectification. Procedures for designing MDS-1(c1,c2) sampling plans with minimum variance of OQ and TI are developed. A procedure for obtaining a plan for a designated upper limit for the variance of the OQ (VOQL) is outlined.

  7. Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA

    Directory of Open Access Journals (Sweden)

    Mayela Rodríguez-Violante

    2014-01-01

    Full Text Available Introduction. Neuropsychiatric symptoms in Parkinson’s disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson’s disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was 2.9±3.1 (range from 0 to 16. The neuropsychiatric MDS-UPDRS part IA score was 2.9±3 (range from 0 to 14. The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was rs=0.93 (all, P<0.001. Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found.

  8. Surface Prognostic Charts

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Surface Prognostic Charts are historical surface prognostic (forecast) charts created by the United States Weather Bureau. They include fronts, isobars, cloud, and...

  9. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults

    Science.gov (United States)

    Babushok, Daria V.; Bessler, Monica; Olson, Timothy S.

    2016-01-01

    Myelodysplastic syndrome (MDS) is a clonal blood disorder characterized by ineffective hematopoiesis, cytopenias, dysplasia and an increased risk of acute myeloid leukemia (AML). With the growing availability of clinical genetic testing, there is an increasing appreciation that a number of genetic predisposition syndromes may underlie apparent de novo presentations of MDS/AML, particularly in children and young adults. Recent findings of clonal hematopoiesis in acquired aplastic anemia add another facet to our understanding of the mechanisms of MDS/AML predisposition. As more predisposition syndromes are recognized, it is becoming increasingly important for hematologists and oncologists to have familiarity with the common as well as emerging syndromes, and to have a systematic approach to diagnosis and screening of at risk patient populations. Here, we provide a practical algorithm for approaching a patient with a suspected MDS/AML predisposition, and provide an in-depth review of the established and emerging familial MDS/AML syndromes caused by mutations in the ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes. Finally, we discuss recent data on the role of somatic mutations in malignant transformation in acquired aplastic anemia, and review the practical aspects of MDS/AML management in patients and families with predisposition syndromes. PMID:26693794

  10. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults.

    Science.gov (United States)

    Babushok, Daria V; Bessler, Monica; Olson, Timothy S

    2016-01-01

    Myelodysplastic syndrome (MDS) is a clonal blood disorder characterized by ineffective hematopoiesis, cytopenias, dysplasia and an increased risk of acute myeloid leukemia (AML). With the growing availability of clinical genetic testing, there is an increasing appreciation that a number of genetic predisposition syndromes may underlie apparent de novo presentations of MDS/AML, particularly in children and young adults. Recent findings of clonal hematopoiesis in acquired aplastic anemia add another facet to our understanding of the mechanisms of MDS/AML predisposition. As more predisposition syndromes are recognized, it is becoming increasingly important for hematologists and oncologists to have familiarity with the common as well as emerging syndromes, and to have a systematic approach to diagnosis and screening of at risk patient populations. Here, we provide a practical algorithm for approaching a patient with a suspected MDS/AML predisposition, and provide an in-depth review of the established and emerging familial MDS/AML syndromes caused by mutations in the ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes. Finally, we discuss recent data on the role of somatic mutations in malignant transformation in acquired aplastic anemia, and review the practical aspects of MDS/AML management in patients and families with predisposition syndromes.

  11. Mutational Profiling of Therapy-related Myelodysplastic Syndromes and Acute Myeloid Leukemia by Next Generation Sequencing, a Comparison with de novo Diseases

    OpenAIRE

    Ok, Chi Young; Patel, Keyur P.; Garcia-Manero, Guillermo; Routbort, Mark J.; Fu, Bin; Tang, Guilin; Goswami, Maitrayee; Singh, Rajesh; Kanagal-Shamanna, Rashmi; Pierce, Sherry A.; Young, Ken H.; Kantarjian, Hagop M.; Medeiros, L. Jeffrey; Luthra, Rajyalakshmi; Wang, Sa A.

    2014-01-01

    In this study we used a next generation sequencing-based approach to profile gene mutations in therapy-related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML); and compared these findings with de novo MDS/AML. Consecutive bone marrow samples of 498 patients, including 70 therapy-related (28 MDS and 42 AML) and 428 de novo (147 MDS and 281 AML) were analyzed using a modified-TruSeq Amplicon Cancer Panel (Illumina) covering mutation hotspots of 53 genes. Overall, mutation(s...

  12. [Inhibitory Effect of Decitabine on Proliferation of MDS-L Cells and Its Mechanism].

    Science.gov (United States)

    Wu, Dong; Zhang, Yao; Zhao, You-Shan; Guo, Juan; Chang, Chun-Kang

    2017-10-01

    To investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism. LC-MS/MS method was used to test the blood DAC concentration of 2 groups of MDS patients being treated with DAC 20 and 15 mg/m 2 ×5 d. In according to the various blood DAC concentration levels, the MDS-L cells were treated with different DAC dosages for 24, 48, 72 and 96 h, respectively. The CCK-8 method was applied to determine the cell proliferation, the flow cytometry was used to analyze the cell cycle and cell apoptosis changes, the P15 INK4B DNA methylation status was measured by methylation specific PCR using EZ DNA Methylation-Gold Kit. The blood DAC concentration of MDS patients treated with DAC 20 mg/m 2 ×5 d was 174.08±80.15(84.7-311) ng/ml, which was significantly higher than 89.87±32.94(43.2-165)ng/ml for the group treated with 15 mg/m 2 ×5 d (P=0.014). DAC could notably inhibit the proliferation of MDS-L cells, and the effect was in dose- and- time-dependent manner(r=0.786). However, when DAC concentration was ≥0.1 µg/ml, the proliferation inhibition rates were not significantly different between various dosages. After DAC treatment, MDS-L cells in G 1 phase increased notably, while cells in S phase decreased significantly. Also, the P15 INK4B DNA methylation status of MDS-L cells decreased after being treated with DAC for 96 h, but the difference was not significant between various dosages. DAC can significantly suppress MDS-L cell proliferation, block MDS-L cells in G 1 phase and induce the apoptosis at low concentration (0.1-0.2 µg/ml).

  13. [PROGNOSTIC SIGNIFICANCE OF ELEMENTS OF THE MULTIORGAN INSUFFICIENCY SYNDROME AND ESTIMATION OF THE PATIENTS STATE SEVERITY IN ACCORDANCE TO INTEGRAL SCALES IN AN ACUTE NECROTIC PANCREATITIS].

    Science.gov (United States)

    Khomyak, I V; Rotar, O V; Rotar, V I; Petrovskiy, G G

    2015-09-01

    There were examined 113 patients, in whom an acute necrotic pancreatitis was diagnosed. While admittance to hospital a constant organ insufficiency was revealed in 50 (44%), a transient one--in 63 (56%) patients. In total 31 (27.4%) patients died. Respiratory insufficiency have occurred in 67% patients, and almost with similar rate--cardio-vascular (in 59%), renal (in 56%) and enteral (in 54%), dominating in the lethality structure. The BISAP (Bedcide Index for Severity in Acute Pancreatitis) scales applied permit with high probability to prognosticate the organ insufficiency and lethality in patients, suffering an acute necrotic pancreatitis.

  14. Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

    Science.gov (United States)

    Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

    2012-08-01

    Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

  15. Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation.

    Science.gov (United States)

    Koenecke, Christian; Göhring, Gudrun; de Wreede, Liesbeth C; van Biezen, Anja; Scheid, Christof; Volin, Liisa; Maertens, Johan; Finke, Jürgen; Schaap, Nicolaas; Robin, Marie; Passweg, Jakob; Cornelissen, Jan; Beelen, Dietrich; Heuser, Michael; de Witte, Theo; Kröger, Nicolaus

    2015-03-01

    The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification. Copyright© Ferrata Storti Foundation.

  16. Sequential acquisition of mutations in myelodysplastic syndromes.

    Science.gov (United States)

    Makishima, Hideki

    2017-01-01

    Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, DDX41 mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms. In MDS, mutations of genes such as NRAS and FLT3, designated as Type-1 genes, may be significantly associated with leukemic evolution. Another type (Type-2) of genes, including RUNX1 and GATA2, are related to progression from low-risk to high-risk MDS. Overall, various driver mutations are sequentially acquired in MDS, at a specific time, in either germline cells, normal hematopoietic cells, or clonal MDS cells.

  17. Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup.

    Science.gov (United States)

    Ciabatti, Elena; Valetto, Angelo; Bertini, Veronica; Ferreri, Maria Immacolata; Guazzelli, Alice; Grassi, Susanna; Guerrini, Francesca; Petrini, Iacopo; Metelli, Maria Rita; Caligo, Maria Adelaide; Rossi, Simona; Galimberti, Sara

    2017-10-03

    In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration. FISH analysis detected chromosomal aberrations in 24% of patients and recovered 5 cases (13.5%) at normal karyotype (two 5q- syndromes, one del(7) case, two cases with PDGFR rearrangement). The aGCH detected 10 "new" unbalanced cases in respect of the CC, including one with alteration of the ETV6 gene. After mutational analysis, 33 patients (54%) presented at least one mutation and represented the only marker of clonality in 36% of all patients. The statistical analysis confirmed the prognostic role of CC either on overall or on progression-free-survival. In addition, deletions detected by aCGH and WT1 over-expression negatively conditioned survival. In conclusion, our work showed that 1) the addition of FISH (at least for chr. 5 and 7) can improve the definition of the risk score; 2) mutational analysis, especially for the TP53 and SF3B1, could better define the type of MDS and represent a "clinical warning"; 3) the aCGH use could be probably applied to selected cases (with suboptimal response or failure).

  18. MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease.

    Science.gov (United States)

    Jafari, Nickey; Pahwa, Rajesh; Nazzaro, Jules M; Arnold, Paul M; Lyons, Kelly E

    2016-01-01

    To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

  19. [TOPICS-MDS: a versatile resource for generating scientific and social knowledge for elderly care].

    Science.gov (United States)

    van den Brink, Danielle; Lutomski, Jennifer E; Qin, Li; den Elzen, Wendy P J; Kempen, Gertrudis I J M; Krabbe, Paul F M; Steyerberg, Ewout W; Muntinga, Maaike; Moll van Charante, Eric P; Bleijenberg, Nienke; Olde Rikkert, Marcel G M; Melis, René J F

    2015-04-01

    Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a standardized questionnaire to collect relevant health care data on quality of life, health services utilization, and informal care use. A proactive approach has been undertaken not only to ensure the standardization and validation of instruments but also the infrastructure for external data requests. Efforts have been made to promote scientifically and socially responsible use of TOPICS-MDS; data has been available for secondary use since early 2014. Through this data sharing initiative, researchers can explore health issues in a broader framework which may have not been possible within individual NPO projects; this broader framework is highly relevant for influencing health policy. In this article, we provide an overview of the development and on-going progress of TOPICS-MDS. We further describe how information derived from TOPICS-MDS can be applied to facilitate future scientific innovations and public health initiatives to improve care for frail older persons and their caregivers.

  20. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

    NARCIS (Netherlands)

    P. Montesinos (Pau); J.M. Bergua (Juan Miguel); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); J. de Serna (Javier); A. León (Angel); J. Esteve (Jordi); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); D.M. Joaquín; J.D. González (José David); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractDifferentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char-

  1. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS

    DEFF Research Database (Denmark)

    Bech Mortensen, Thomas; Frederiksen, Henrik; Marcher, Claus Werenberg

    2017-01-01

    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological featu...

  2. [Changes of CD34(+) and CD71(+)CD45(-) cell levels in bone marrow of MDS and AA patients].

    Science.gov (United States)

    Yan, Zhen-Yu; Tian, Xu; Li, Ying; Yang, Mei-Rong; Zhang, Song; Wang, Xie-Ming; Zhang, Hai-Xia; Cheng, Nai-Yao

    2014-04-01

    This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or MDS group was higher than that in AA (NSAA and SAA) group (P MDS group was higher than that in SAA (P MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P MDS and NSAA group with CD71(+)CD45(-) 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.

  3. The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice.

    Science.gov (United States)

    Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore

    2012-01-01

    The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

  4. The Mice Drawer System (MDS experiment and the space endurance record-breaking mice.

    Directory of Open Access Journals (Sweden)

    Ranieri Cancedda

    Full Text Available The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS, contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS. The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th, 2009. MDS returned to Earth on November 27(th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

  5. Parkinson's disease severity levels and MDS-Unified Parkinson's Disease Rating Scale.

    Science.gov (United States)

    Martínez-Martín, Pablo; Rodríguez-Blázquez, Carmen; Mario Alvarez; Arakaki, Tomoko; Arillo, Víctor Campos; Chaná, Pedro; Fernández, William; Garretto, Nélida; Martínez-Castrillo, Juan Carlos; Rodríguez-Violante, Mayela; Serrano-Dueñas, Marcos; Ballesteros, Diego; Rojo-Abuin, Jose Manuel; Chaudhuri, Kallol Ray; Merello, Marcelo

    2015-01-01

    Severity of PD is usually assessed by means of the motor and disability-based Hoehn and Yahr staging (HY), or clinician and patient global perceptions. Scores of more detailed assessments, as the MDS-UPDRS, have not been translated to a grading that allows assignment of score sections to severity levels. The objective of the present study is to determine cut-off points for PD severity levels based on the MDS-UPDRS. International, observational study. Applied assessments were: HY, MDS-UPDRS, Clinical Impression for Severity Index, and Clinical and Patient Global Impression of Severity. The coincidence in severity level (mild, moderate, severe) of at least two clinical classifications plus the patient's gradation was considered "the criterion of severity". Cut-off values for each MDS-UPDRS subscale was determined by triangulation of: 1) percentile 90 of the subscale total score; 2) receiver operating characteristic (ROC) analysis; and 3) ordinal logistic regression (OLR) model. Sample was composed of 452 consecutive PD patients without dementia, 55.3% males, age 65.1 ± 10.7 years and PD duration 8.7 ± 6.3 years. All HY stages were represented. The "criterion", classified 275 patients (60.8% of the sample) as: mild PD, 149 (54.2%); moderate, 82 (29.8%); and severe, 44 (16%). The following MDS-UPDRS cut-off points between mild/moderate and moderate/severe levels were found: Part 1: 10/11 and 21/22; Part 2: 12/13 and 29/30; Part 3: 32/33 and 58/59; and Part 4: 4/5 and 12/13. Cut-off points to classify PD patients as mild, moderate, or severe on the basis of their MDS-UPDRS scores are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. RECENT ADVANCES IN THE 5Q- SYNDROME

    Directory of Open Access Journals (Sweden)

    Andrea Pellagatti

    2015-05-01

    Full Text Available The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS and patients with this disorder have a deletion of chromosome 5q [del(5q] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathogenesis in recent years. Haploinsufficiency of the ribosomal gene RPS14 has been shown to cause the erythroid defect in the 5q- syndrome. Loss of the microRNA genes miR-145 and miR-146a has been associated with the thrombocytosis observed in 5q- syndrome patients. Haploinsufficiency of CSNK1A1 leads to hematopoietic stem cell expansion in mice and may play a role in the initial clonal expansion in patients with 5q- syndrome. Moreover, a subset of patients harbor mutation of the remaining CSNK1A1 allele. Mouse models of the 5q- syndrome, which recapitulate the key features of the human disease, indicate that a p53-dependent mechanism underlies the pathophysiology of this disorder. Importantly, activation of p53 has been demonstrated in the human 5q- syndrome. Recurrent TP53 mutations have been associated with an increased risk of disease evolution and with decreased response to the drug lenalidomide in del(5q MDS patients. Potential new therapeutic agents for del(5q MDS include the translation enhancer L-leucine.

  7. Hypomethylating Agents and Other Novel Strategies in Myelodysplastic Syndromes

    Science.gov (United States)

    Garcia-Manero, Guillermo; Fenaux, Pierre

    2011-01-01

    Over the last decade, treatment approaches for patients with myelodysplastic syndromes (MDS) have improved significantly. Treatment of MDS is tailored to the specific risk characteristics of the patient. In general, patients are divided into lower- and higher-risk categories. Without therapy, prognosis of patients with higher-risk MDS is poor, and treatments should be directed to improve survival. Prognosis of patients with lower-risk MDS is more heterogeneous, and therapies are usually directed to minimize transfusion needs and potentially to alter the natural course of the disease. Treatment options for patients with higher-risk MDS include hypomethylating agents (azacitidine and decitabine), intensive chemotherapy (ICT), and allogeneic stem-cell transplantation (alloSCT). The use of the hypomethylating agents has transformed the approach to this patient population, in particular older individuals, for whom ICT and alloSCT are not an option. In lower-risk MDS, treatment strategies are used sequentially and usually include observation in patients with low risk and no transfusion dependency, growth factors, and lenalidomide for patients with alteration of chromosome 5 and anemia. The use of hypomethylating agents is less understood in this group of patients. AlloSCT is usually reserved for patients with lower-risk MDS closer to the time of transformation. In this short review, we discuss treatment alternatives for patients with MDS and delineate some of the ongoing challenges, including the development of better front-line strategies for patients with higher-risk disease, the concept of altering the natural course of the disease in lower-risk MDS, and the development of new treatment approaches for patients who do not benefit from hypomethylating agents. PMID:21220589

  8. Prognostics for Microgrid Components

    Science.gov (United States)

    Saxena, Abhinav

    2012-01-01

    Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

  9. Prognostic Performance Metrics

    Data.gov (United States)

    National Aeronautics and Space Administration — This chapter presents several performance metrics for offline evaluation of prognostics algorithms. A brief overview of different methods employed for performance...

  10. Lenalidomid til behandling af transfusionskraevende myelodysplastisk syndrom

    DEFF Research Database (Denmark)

    Risum, Malene; Dufva, I.H.

    2010-01-01

    Lenalidomide is the first drug to induce transfusion independence and cytogenetic remission in patients with myelodysplastic syndrome (MDS) with deletion 5q and low or intermediate risk score. Transfusion independence can be obtained within five weeks. Three out of four patients also obtain...

  11. Microcephaly, microtia, preauricular tags, choanal atresia and developmental delay in three unrelated patients: a mandibulofacial dysostosis distinct from Treacher Collins syndrome.

    NARCIS (Netherlands)

    Wieczorek, D.; Gener, B.; Gonzalez, M.J.; Seland, S.; Fischer, S.; Hehr, U.; Kuechler, A.; Hoefsloot, L.H.; Leeuw, N. de; Gillessen-Kaesbach, G.; Lohmann, D.R.

    2009-01-01

    Treacher Collins syndrome (TCS, OMIM 154500) is a well-defined mandibulofacial dysostosis characterized by symmetric facial anomalies consisting of malar hypoplasia, coloboma of the lower eyelid, dysplastic ears, micrognathia, cleft palate and deafness. Other mandibulofacial dysostoses (MDs) such as

  12. Some aspects of allogeneic stem cell transplantation in patients with myelodysplastic syndrome: advances and controversy

    Directory of Open Access Journals (Sweden)

    Blau O

    2014-12-01

    Full Text Available Olga Blau, Igor Wolfgang Blau Department of Hematology, Oncology and Tumor Immunology, Charité – Universitätsmedizin Berlin, Berlin, Germany Abstract: Myelodysplastic syndrome (MDS is a heterogeneous group of myeloid disorders. MDS remains a disease of elderly patients; moreover, the incidence of high risk MDS is proportionally greater in elderly patients, with increased frequency of secondary acute myeloid leukemia, as well as adverse cytogenetic abnormalities. Allogeneic stem cell transplantation is a therapeutic approach with known curative potential for patients with MDS that allows the achievement of long-term disease control. Numerous controversies still exist regarding transplantation in MDS: timing of transplantation, disease status at transplantation and comorbidity, conditioning intensity, pretransplant therapy, and stem cell source. Various transplant modalities of different intensities and alternative donor sources are now in use. Current advances in transplant technology are allowing the consideration of older patients. This should result in a greater number of older patients benefiting from this potentially curative treatment modality. Despite advances in transplantation technology, there is still considerable morbidity and mortality associated with this approach. Nevertheless, with the introduction of reduced-intensity conditioning and thereby reduced early mortality, transplant numbers in MDS patients have significantly increased. Moreover, recent new developments with innovative drugs, including hypomethylating agents, have extended the therapeutic alternatives for MDS patients. Hypomethylating agents allow the delay of allogeneic stem cell transplantation by serving as an effective and well-tolerated means to reduce disease burden. Keywords: myelodysplastic syndrome, allogeneic stem cell transplantation, reduced-intensity conditioning

  13. FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities

    International Nuclear Information System (INIS)

    L’Abbate, Alberto; Tagliafico, Enrico; Minoia, Carla; De Tullio, Giacoma; Guarini, Attilio; Testoni, Nicoletta; Agostinelli, Claudio; Storlazzi, Clelia Tiziana; Lo Cunsolo, Crocifissa; Macrì, Ettore; Iuzzolino, Paolo; Mecucci, Cristina; Doglioni, Claudio; Coco, Michelina; Muscarella, Lucia Anna; Salati, Simona

    2014-01-01

    The progression of low-risk del(5q) myelodysplastic syndrome to acute myeloid leukemia is increased when associated with mutations of TP53, or with additional chromosomal abnormalities. However, to date the prognostic impact and molecular consequences of these rearrangements were poorly investigated. Single additional alterations to del(5q) by balanced chromosome rearrangements were rarely found in myelodysplasia. In particular, balanced alterations involving TP63 and FOXP1 genes were never reported in the literature. Here we report on a 79-year woman with an aggressive form of myelodysplastic syndrome with del(5q), no TP53 mutation, and a novel complex rearrangement of chromosome 3 in bone marrow cells. Our results revealed that the FOXP1 and TP63 genes were both relocated along chromosome 3. Strikingly, immunohistochemistry analysis showed altered protein levels, disclosing that this rearrangement triggered the expression of FOXP1 and TP63 genes. FOXP1 was also found activated in other patients with myelodysplasia and acute myeloid leukemia, showing that it is an important, recurrent event. We document an apparent role of FOXP1 and TP63, up to now poorly documented, in the progression of MDS in our patient who is lacking mutations in the TP53 tumor suppressor gene normally associated with poor outcome in myelodysplastic syndrome with 5q-. Finally, our results may suggest a possible broader role of FOXP1 in the pathogenesis and progression of myelodysplasia and acute myeloid leukemia

  14. Myelodysplastic syndromes in Chernobyl clean-up workers.

    Science.gov (United States)

    Gluzman, Daniil F; Sklyarenko, Lilia M; Koval, Stella V; Rodionova, Nataliia K; Zavelevich, Michael P; Ivanivskaya, Tetiana S; Poludnenko, Liudmyla Yu; Ukrainskaya, Nataliia I

    2015-10-01

    The studies of the recent decades posed the question of the association between radiation exposure and myelodysplastic syndromes (MDS). This association has been proved in secondary MDS originating upon exposure to chemotherapeutics and/or radiation therapy. The long-term study in Japanese atomic (A)-bomb survivors demonstrated the significant linear dose-response for MDS confirming the link between radiation exposure and this form of hematopoietic malignancies. All these findings provide the strong basis for studying MDS in the persons exposed to radiation following the Chernobyl disaster, especially those in the cohort of Chernobyl clean-up workers of 1986-1987. The data on MDS among Chernobyl clean-up workers (1986-1987) diagnosed in 1996-2012 at the reference laboratory of RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology are summarized. MDS cases were diagnosed in 23 persons (21 males and 2 females) having been exposed to radiation as clean-up workers of 1986-1987. Refractory anemia (RA) has been detected in 13, refractory anemia with ring sideroblasts (RARS)-in 2, and refractory anemia with excess blasts (RAEB)-in 8 patients. The median age of those MDS patients was 62.0 years. In addition, 5 cases of chronic myelomonocytic leukemia (CMML) were recorded in the group of Chernobyl clean-up workers with the median time of 14.8 years from 1986-1987 to diagnosis. The association between radiation exposure and MDS is discussed. The suggested life-long risk for myelodysplastic syndromes among A-bomb survivors in Japan highlights the importance of the continuing follow-up studies in the affected populations in the post-Chernobyl period.

  15. Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome with Ring Sideroblasts and Multilineage Dysplasia

    Directory of Open Access Journals (Sweden)

    Jacob D. Kjelland

    2017-01-01

    Full Text Available Acquired elliptocytosis is a known but rarely described abnormality in the myelodysplastic syndromes (MDS. Here we report the case of an elderly male who was admitted to the hospital with chest pain, dyspnea, and fatigue and was found to be anemic with an elliptocytosis that had only recently been noted on peripheral smears of his blood. After bone marrow biopsy he was diagnosed with MDS with ring sideroblasts and multilineage dysplasia and acquired elliptocytosis. Here we report a rare case of acquired elliptocytosis cooccurring with MDS with ring sideroblasts and multilineage dysplasia.

  16. Mutational Profiling of Therapy-related Myelodysplastic Syndromes and Acute Myeloid Leukemia by Next Generation Sequencing, a Comparison with de novo Diseases

    Science.gov (United States)

    Ok, Chi Young; Patel, Keyur P.; Garcia-Manero, Guillermo; Routbort, Mark J.; Fu, Bin; Tang, Guilin; Goswami, Maitrayee; Singh, Rajesh; Kanagal-Shamanna, Rashmi; Pierce, Sherry A.; Young, Ken H.; Kantarjian, Hagop M.; Medeiros, L. Jeffrey; Luthra, Rajyalakshmi; Wang, Sa A.

    2017-01-01

    In this study we used a next generation sequencing-based approach to profile gene mutations in therapy-related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML); and compared these findings with de novo MDS/AML. Consecutive bone marrow samples of 498 patients, including 70 therapy-related (28 MDS and 42 AML) and 428 de novo (147 MDS and 281 AML) were analyzed using a modified-TruSeq Amplicon Cancer Panel (Illumina) covering mutation hotspots of 53 genes. Overall, mutation(s) were detected in 58.6% of t-MDS/AML and 56.8% of de novo MDS/AML. Of therapy-related cases, mutations were detected in 71.4% of t-AML versus 39.3% t-MDS (p=0.0127). TP53 was the most common mutated gene in t-MDS (35.7%) as well as t-AML (33.3%), significantly higher than de novo MDS (17.7%) (p=0.0410) and de novo AML (12.8%) (p=0.0020). t-AML showed more frequent PTPN11 but less NPM1 and FLT3 mutations than de novo AML. In summary, t-MDS/AML shows a mutation profile different from their de novo counterparts. TP53 mutations are highly and similarly prevalent in t-MDS and t-AML but mutations in genes other than TP53 were more frequent in t-AML than t-MDS. The molecular genetic profiling further expands our understanding in this group of clinically aggressive yet heterogeneous myeloid neoplasms. PMID:25573287

  17. Mouse Drawer System (MDS): An autonomous hardware for supporting mice space research

    Science.gov (United States)

    Liu, Y.; Biticchi, R.; Alberici, G.; Tenconi, C.; Cilli, M.; Fontana, V.; Cancedda, R.; Falcetti, G.

    2005-08-01

    For the scientific community the ability of flying mice under weightless conditions in space, compared to other rodents, offers many valuable advantages. These include the option of testing a wide range of wild-type and mutant animals, an increased animal number for flight, and a reduced demand on shuttle resources and crew time. In this study, we describe a spaceflight hardware for mice, the Mouse Drawer System (MDS). MDS can interface with Space Shuttle middeck and International Space Station Express Rack. It consists of Mice Chamber, Liquid Handling Subsystem, Food Delivery Subsystem, Air Conditioning Subsystem, Illumination Subsystem, Observation Subsystem and Payload Control Unit. It offers single or paired containment for 6-8 mice with a mean weight of 40 grams/mouse for a period of up to 3 months. Animal tests were conducted in a MDS breadboard to validate the biocompatibility of various subsystems. Mice survived in all tests of short and long duration. Results of blood parameters, histology and air/waste composition analysis showed that MDS subsystems meet the NIH guidelines for temperature, humidity, food and water access, air quality, odour and waste management.

  18. Assessing the Mechanisms of MDS and Its Transformation to Leukemia in a Novel Humanized Mouse

    Science.gov (United States)

    2016-05-01

    for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188...grade MDS with replication of the disease geno- and phenotypes. Inventions, Patents and Licences N/A Reportable Outcomes N/A Other

  19. Prognostic methods in medicine

    NARCIS (Netherlands)

    Lucas, P. J.; Abu-Hanna, A.

    1999-01-01

    Prognosis--the prediction of the course and outcome of disease processes--plays an important role in patient management tasks like diagnosis and treatment planning. As a result, prognostic models form an integral part of a number of systems supporting these tasks. Furthermore, prognostic models

  20. Aircraft Anomaly Prognostics, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Ridgetop Group will leverage its proven Electromechanical Actuator (EMA) prognostics methodology to develop an advanced model-based actuator prognostic reasoner...

  1. GPU Accelerated Prognostics

    Science.gov (United States)

    Gorospe, George E., Jr.; Daigle, Matthew J.; Sankararaman, Shankar; Kulkarni, Chetan S.; Ng, Eley

    2017-01-01

    Prognostic methods enable operators and maintainers to predict the future performance for critical systems. However, these methods can be computationally expensive and may need to be performed each time new information about the system becomes available. In light of these computational requirements, we have investigated the application of graphics processing units (GPUs) as a computational platform for real-time prognostics. Recent advances in GPU technology have reduced cost and increased the computational capability of these highly parallel processing units, making them more attractive for the deployment of prognostic software. We present a survey of model-based prognostic algorithms with considerations for leveraging the parallel architecture of the GPU and a case study of GPU-accelerated battery prognostics with computational performance results.

  2. Gender-, age- and race/ethnicity-based Differential Item Functioning (DIF) analysis of MDS-UPDRS

    Science.gov (United States)

    Goetz, Christopher G.; Liu, Yuanyuan; Stebbins, Glenn T.; Wang, Lu; Tilley, Barbara C.; Teresi, Jeanne A.; Merkitch, Douglas; Luo, Sheng

    2016-01-01

    Objective Assess MDS-UPDRS items for gender-, age-, and race/ethnicity-based Differential Item Functioning. Background Assessing Differential Item Functioning is a core rating scale validation step. For the MDS-UPDRS, Differential Item Functioning occurs if item-score probability among people with similar levels of parkinsonism differ according to selected covariates (gender, age, race/ethnicity). If the magnitude of Differential Item Functioning is clinically relevant, item-score interpretation must consider influences by these covariates. Differential Item Functioning can be Non-uniform (covariate variably influences an item-score across different levels of parkinsonism) or Uniform (covariate influences an item-score consistently over all levels of parkinsonism. Methods Using the MDS-UPDRS translation database of over 5,000 PD patients from fourteen languages, we tested gender-, age-, and race/ethnicity-based Differential Item Functioning. To designate an item as having clinically relevant Differential Item Functioning, we required statistical confirmation by two independent methods, along with a McFadden pseudo-R2 magnitude statistic greater than “negligible.” Results Most items showed no gender-, age- or race/ethnicity-based Differential Item Functioning. When Differential Item Functioning was identified, the magnitude statistic was always in the “negligible” range, and the scale level impact was minimal. Conclusions The absence of clinically relevant Differential Item Functioning across all items and all Parts of MDS-UPDRS is strong evidence that the scale can be used confidently. As studies of Parkinson's disease increasingly involve multinational efforts and the MDS-UPDRS has several validated non-English translations, the findings support the scale's broad applicability in populations with varying gender, age, and race/ethnicity distributions. PMID:27943473

  3. Development of a Minimum Data Set (MDS) for C-Section Anesthesia Information Management System (AIMS).

    Science.gov (United States)

    Sheykhotayefeh, Mostafa; Safdari, Reza; Ghazisaeedi, Marjan; Khademi, Seyed Hossein; Seyed Farajolah, Seyedeh Sedigheh; Maserat, Elham; Jebraeily, Mohamad; Torabi, Vahid

    2017-04-01

    Caesarean section, also known as C-section, is a very common procedure in the world. Minimum data set (MDS) is defined as a set of data elements holding information regarding a series of target entities to provide a basis for planning, management, and performance evaluation. MDS has found a great use in health care information systems. Also, it can be considered as a basis for medical information management and has shown a great potential for contributing to the provision of high quality care and disease control measures. The principal aim of this research was to determine MDS and required capabilities for Anesthesia information management system (AIMS) in C-section in Iran. Data items collected from several selected AIMS were studied to establish an initial set of data. The population of this study composed of 115 anesthesiologists was asked to review the proposed data elements and score them in order of importance by using a five-point Likert scale. The items scored as important or highly important by at least 75% of the experts were included in the final list of minimum data set. Overall 8 classes of data (consisted of 81 key data elements) were determined as final set. Also, the most important required capabilities were related to airway management and hypertension and hypotension management. In the development of information system (IS) based on MDS and identification, because of the broad involvement of users, IS capabilities must focus on the users' needs to form a successful system. Therefore, it is essential to assess MDS watchfully by considering the planned uses of data. Also, IS should have essential capabilities to meet the needs of its users.

  4. Impact of age and gender on the prevalence and prognostic importance of the metabolic syndrome and its components in Europeans. The MORGAM Prospective Cohort Project

    DEFF Research Database (Denmark)

    Vishram, Julie K K; Borglykke, Anders; Andreasen, Anne H

    2014-01-01

    of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII), increased across age groups for both genders (P...OBJECTIVE: To investigate the influence of age and gender on the prevalence and cardiovascular disease (CVD) risk in Europeans presenting with the Metabolic Syndrome (MetS). METHODS: Using 36 cohorts from the MORGAM-Project with baseline between 1982-1997, 69094 men and women aged 19-78 years......, without known CVD, were included. During 12.2 years of follow-up, 3.7%/2.1% of men/women died due to CVD. The corresponding percentages for fatal and nonfatal coronary heart disease (CHD) and stroke were 8.3/3.8 and 3.1/2.5. RESULTS: The prevalence of MetS, according to modified definitions...

  5. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial

    International Nuclear Information System (INIS)

    Tobiasson, M; Dybedahl, I; Holm, M S; Karimi, M; Brandefors, L; Garelius, H; Grövdal, M; Högh-Dufva, I; Grønbæk, K; Jansson, M; Marcher, C; Nilsson, L; Kittang, A O; Porwit, A; Saft, L; Möllgård, L; Hellström-Lindberg, E

    2014-01-01

    This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of ⩾4 units over 8 weeks were included. Aza 75 mg m −2 d −1 , 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received ⩾one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations

  6. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial.

    Science.gov (United States)

    Tobiasson, M; Dybedahl, I; Holm, M S; Karimi, M; Brandefors, L; Garelius, H; Grövdal, M; Högh-Dufva, I; Grønbæk, K; Jansson, M; Marcher, C; Nilsson, L; Kittang, A O; Porwit, A; Saft, L; Möllgård, L; Hellström-Lindberg, E

    2014-03-07

    This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of 4 units over 8 weeks were included. Aza 75 mg m(-2) d(-1), 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations.

  7. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)

    2008-06-15

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

  8. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression.

    Science.gov (United States)

    Jädersten, Martin; Saft, Leonie; Smith, Alexander; Kulasekararaj, Austin; Pomplun, Sabine; Göhring, Gudrun; Hedlund, Anette; Hast, Robert; Schlegelberger, Brigitte; Porwit, Anna; Hellström-Lindberg, Eva; Mufti, Ghulam J

    2011-05-20

    To determine the frequency of TP53 mutations and the level of p53 protein expression by immunohistochemistry (IHC) in low-risk myelodysplastic syndromes (MDS) with del(5q) and to assess their impact on disease progression. Pre- and postprogression bone marrow (BM) samples from 55 consecutive patients with International Prognostic Scoring System low risk (n = 32) or intermediate-1 risk (n = 23) were studied by next-generation sequencing of TP53. IHC for p53 was performed on 148 sequential BM samples. TP53 mutations with a median clone size of 11% (range, 1% to 54%) were detected in 10 patients (18%) already at an early phase of the disease. Mutations were equally common in low-risk and intermediate-1-risk patients and were associated with evolution to acute myeloid leukemia (5 of 10 v 7 of 45; P = .045). Nine of 10 patients carrying mutations showed more than 2% BM progenitors with strong p53 staining. The probability of a complete cytogenetic response to lenalidomide was lower in mutated patients (0 of 7 v 12 of 24; P = .024). By using sensitive deep-sequencing technology, we demonstrated that TP53 mutated populations may occur at an early disease stage in almost a fifth of low-risk MDS patients with del(5q). Importantly, mutations were present years before disease progression and were associated with an increased risk of leukemic evolution. TP53 mutations could not be predicted by common clinical features but were associated with p53 overexpression. Our findings indicate a previously unrecognized heterogeneity of the disease which may significantly affect clinical decision making.

  9. No prognostic significance of chronic infection with Chlamydia pneumoniae in acute coronary syndromes: insights from the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial

    DEFF Research Database (Denmark)

    Westerhout, Cynthia M; Gnarpe, Judy; Chang, Wei-Ching

    2007-01-01

    BACKGROUND: Although relationships between chronic Chlamydia pneumoniae (Cpn) infection and the risk of coronary events in stable coronary artery disease patients have been reported, a similar link in acute coronary syndrome (ACS) patients has not been consistently observed. METHODS: In a nested ...

  10. Validity of the RAI-MDS for ascertaining diabetes and comorbid conditions in long-term care facility residents.

    Science.gov (United States)

    Lix, Lisa M; Yan, Lin; Blackburn, David; Hu, Nianping; Schneider-Lindner, Verena; Teare, Gary F

    2014-01-15

    This study assessed the validity of the Resident Assessment Instrument Minimum Data Set (RAI-MDS) Version 2.0 for diagnoses of diabetes and comorbid conditions in residents of long-term care facilities (LTCFs). Hospital inpatient, outpatient physician billing, RAI-MDS, and population registry data for 1997 to 2011 from Saskatchewan, Canada were used to ascertain cases of diabetes and 12 comorbid conditions. Prevalence estimates were calculated for both RAI-MDS and administrative health data. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated using population-based administrative health data as the validation data source. Cohen's κ was used to estimate agreement between the two data sources. 23,217 LTCF residents were in the diabetes case ascertainment cohort. Diabetes prevalence was 25.3% in administrative health data and 21.9% in RAI-MDS data. Overall sensitivity of a RAI-MDS diabetes diagnoses was 0.79 (95% CI: 0.79, 0.80) and the PPV was 0.92 (95% CI: 0.91, 0.92), when compared to administrative health data. Sensitivity of the RAI-MDS for ascertaining comorbid conditions ranged from 0.21 for osteoporosis to 0.92 for multiple sclerosis; specificity was high for most conditions. RAI-MDS clinical assessment data are sensitive to ascertain diabetes cases in LTCF populations when compared to administrative health data. For many comorbid conditions, RAI-MDS data have low validity when compared to administrative data. Risk-adjustment measures based on these comorbidities might not produce consistent results for RAI-MDS and administrative health data, which could affect the conclusions of studies about health outcomes and quality of care across facilities.

  11. Myelodysplastic syndromes: therapeutic problems and decisions (review

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

  12. Myelodysplastic syndromes: therapeutic problems and decisions (review

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2014-07-01

    Full Text Available Myelodysplastic syndromes (MDS are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

  13. Prevalence and prognostic value of acute cor pulmonale and patent foramen ovale in ventilated patients with early acute respiratory distress syndrome: a multicenter study.

    Science.gov (United States)

    Lhéritier, Gwenaëlle; Legras, Annick; Caille, Agnès; Lherm, Thierry; Mathonnet, Armelle; Frat, Jean-Pierre; Courte, Anne; Martin-Lefèvre, Laurent; Gouëllo, Jean-Paul; Amiel, Jean-Bernard; Garot, Denis; Vignon, Philippe

    2013-10-01

    We sought to determine the prevalence of and factors associated with acute cor pulmonale (ACP) and patent foramen ovale (PFO) at the early phase of acute respiratory distress syndrome (ARDS), and to assess their relation with mortality. In this prospective multicenter study, 200 patients submitted to protective ventilation for early moderate to severe ARDS [PaO₂/F(I)O₂: 115 ± 39 with F(I)O₂: 1; positive end-expiratory pressure (PEEP): 10.6 ± 3.1 cmH2O] underwent transthoracic (TTE) and transesophageal echocardiography (TEE) 60 mmHg was strongly associated with ACP [odds ratio (OR) 3.70; 95% CI 1.32-10.38; p = 0.01]. No factor was independently associated with PFO, with only a trend for age (OR 2.07; 95% CI 0.91-4.72; p = 0.08). Twenty-eight-day mortality was 23%. Plateau pressure (OR 1.15; 95% CI 1.05-1.26; p < 0.01) and air leaks (OR 5.48; 95% CI 1.30-22.99; p = 0.02), but neither ACP nor PFO, were independently associated with outcome. TEE screening allowed identification of ACP in one-fourth of patients submitted to protective ventilation for early moderate to severe ARDS. PFO shunting was less frequent and never large or extensive. ACP and PFO were not related to outcome.

  14. Prognostic comparison between creatinine-based glomerular filtration rate formulas for the prediction of 10-year outcome in patients with non-ST elevation acute coronary syndrome treated by percutaneous coronary intervention.

    Science.gov (United States)

    Ballo, Piercarlo; Chechi, Tania; Spaziani, Gaia; Fibbi, Veronica; Conti, Duccio; Ferro, Giuseppe; Nigrelli, Santi; Dattolo, Pietro; Fazi, Antonio; Santoro, Giovanni Maria; Zuppiroli, Alfredo; Pizzarelli, Francesco

    2017-03-01

    Estimated glomerular filtration rate (eGFR) is a predictor of outcome among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), but which estimation formula provides the best long-term risk stratification in this setting is still unclear. We compared the prognostic performance of four creatinine-based formulas for the prediction of 10-year outcome in a NSTE-ACS population treated by percutaneous coronary intervention. In 222 NSTE-ACS patients submitted to percutaneous coronary intervention, eGFR was calculated using four formulas: Cockcroft-Gault, re-expressed modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-Epi), and Mayo-quadratic. Predefined endpoints were all-cause death and a composite of cardiovascular death, non-fatal reinfarction, clinically driven repeat revascularisation, and heart failure hospitalisation. The different eGFR values showed poor agreement, with prevalences of renal dysfunction ranging from 14% to 35%. Over a median follow-up of 10.2 years, eGFR calculated by the CKD-Epi and Mayo-quadratic formulas independently predicted outcome, with an increase in the risk of death and events by up to 17% and 11%, respectively, for each decrement of 10 ml/min/1.73 m 2 . The Cockcroft-Gault and MDRD equations showed a borderline association with mortality and did not predict events. When compared in terms of goodness of fit, discrimination and calibration, the Mayo-quadratic outperformed the other formulas for the prediction of death and the CKD-Epi showed the best performance for the prediction of events (net reclassification improvement values 0.33-0.35). eGFR is an independent predictor of long-term outcome in patients with NSTE-ACS treated by percutaneous coronary intervention. The Mayo-quadratic and CKD-Epi equations might be superior to classic eGFR formulas for risk stratification in these patients.

  15. Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Grövdal, Michael; Khan, Rasheed; Aggerholm, Anni

    2007-01-01

    was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard.......008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect...

  16. Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

    Directory of Open Access Journals (Sweden)

    Marianna Guida

    2014-01-01

    Full Text Available A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(PH oxidase (Nox complexes, are frequently activated in AML (acute myeloid leukemia blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML.

  17. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies.

    Science.gov (United States)

    Damaj, Gandhi; Duhamel, Alain; Robin, Marie; Beguin, Yves; Michallet, Mauricette; Mohty, Mohamad; Vigouroux, Stephane; Bories, Pierre; Garnier, Alice; El Cheikh, Jean; Bulabois, Claude-Eric; Huynh, Anne; Bay, Jacques-Olivier; Legrand, Faeyzeh; Deconinck, Eric; Fegueux, Nathalie; Clement, Laurence; Dauriac, Charles; Maillard, Natacha; Cornillon, Jérôme; Ades, Lionel; Guillerm, Gaelle; Schmidt-Tanguy, Aline; Marjanovic, Zora; Park, Sophie; Rubio, Marie-Thérèse; Marolleau, Jean-Pierre; Garnier, Federico; Fenaux, Ierre; Yakoub-Agha, Ibrahim

    2012-12-20

    To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning. With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM. With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.

  18. Metabolic syndrome components as markers to prognosticate the risk of developing chronic kidney disease: evidence-based study with 6492 individuals.

    Science.gov (United States)

    Zomorrodian, Davoud; Khajavi-Rad, Abolfazl; Avan, Amir; Ebrahimi, Mahmoud; Nematy, Mohsen; Azarpazhooh, Mahmoud Reza; Emamian, Marzieh; Sadeghzade, Mahsa; Mirhafez, Seyed Reza; Mohammadi, Maryam; Mousavi, Mina; Esmaeili, Habibollah; Moohebati, Mohsen; Parizadeh, Mohammad Reza; Ferns, Gordon A; Ghayour-Mobarhan, Majid

    2015-06-01

    The global prevalence of metabolic syndrome (MetS) appears to be increasing and the impact of this condition on potential comorbidities such as cardiovascular disease is high. Chronic kidney disease (CKD) is also a potential comorbidity of MetS but the method of screening for this is somewhat controversial. Thus, predictive markers that can predict the risk of developing CKD are warranted for identification of patients with MetS at an increased risk. We investigated the occurrence of CKD in 6492 individuals, either with or without MetS. Our results showed that the prevalence of CKD was markedly higher in those individuals with MetS, and increased progressively with the number of MetS components and age. Waist circumference, triglycerides and high-density lipoprotein cholesterol were significantly (pcreatinine, and were related to the increased risk of CKD (eg, OR 1.293 (95% CI 1.10 to 1.52; p=0.002)). The relative risk of CKD remained statistically significant for uric acid following multivariate analyses and adjusting for MetS-associated factors. Our data demonstrated the association of MetS components with CKD in our population and revealed that susceptibility to CKD was increased with the number of defining features of MetS. These findings prompt prospective studies to determine the impact of preventing and detecting MetS on the risk of developing CKD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Prognostics of Power MOSFET

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and...

  20. Anemia as the Main Manifestation of Myelodysplastic Syndromes.

    Science.gov (United States)

    Santini, Valeria

    2015-10-01

    Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and their most dramatic clinical manifestations. Anemia in MDS is due to ineffective erythropoiesis, with a high degree of apoptosis of marrow erythroid progenitors. These progenitors show distinctive dysplastic features that consent diagnosis, and are recognizable and differentiated, although not easily, from other morphologic alterations present in other types of anemia. Reaching the diagnosis of MDS in a macrocytic anemia and alleviating the symptoms of anemia are therefore an essential objective of the treating physician. In this work, the signs and symptoms of anemia in MDS, as well as its peculiar pathophysiology, are discussed. Erythopoietic stimulating agents (ESAs) are providing the best treatment for anemic MDS patients, but their use is still not approved by health agencies. While still waiting for this waiver, their clinical use is widespread and their effectivness is well known, as well as the dismal prognosis of patients who do not respond to ESAs and require transfusions. MDS with del5q constitute a unique model of anemia whose complex pathophysiology has been clarified at least partially, defining its link to ribosomal alterations likewise what observed in hereditary anemias like Blackfan Diamond anemia. Lenalidomide is the agent that has shown striking and specific erythropoietic activity in del5q MDS, and the basis of this response is starting to be understood. Several new agents are under evaluation for ESA refractory/relapsed MDS patients, targeting different putative mechanisms of ineffective erythropoiesis, and are here reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site

    OpenAIRE

    Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University

    2008-01-01

    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients wi...

  2. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial

    OpenAIRE

    Tobiasson, Magnus; Dybedal, Ingunn; Holm, Mette Skov; Karimi, Mohsen; Brandefors, Lena; Garelius, Hege; Grövdal, Michael; Høgh-Dufva, Inge; Grønbæk, Kirsten; Jansson, Monika; Marcher, Vlaus Werenberg; Nilsson, Lars Håkan; Kittang, Astrid Marta Olsnes; Porwit, Anna; Saft, Leonie

    2014-01-01

    This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of greater than or equal to4 units over 8 weeks were included. Aza 75 mg m−2 d−1, 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with E...

  3. Inhibition of apoptosis by BCL2 prevents leukemic transformation of a murine myelodysplastic syndrome

    Science.gov (United States)

    Saw, Jesslyn; Jowett, Jeremy B. M.; Aplan, Peter D.; Strasser, Andreas; Jane, Stephen M.; Curtis, David J.

    2012-01-01

    Programmed cell death or apoptosis is a prominent feature of low-risk myelodysplastic syndromes (MDS), although the underlying mechanism remains controversial. High-risk MDS have less apoptosis associated with increased expression of the prosurvival BCL2-related proteins. To address the mechanism and pathogenic role of apoptosis and BCL2 expression in MDS, we used a mouse model resembling human MDS, in which the fusion protein NUP98-HOXD13 (NHD13) of the chromosomal translocation t(2;11)(q31;p15) is expressed in hematopoietic cells. Hematopoietic stem and progenitor cells from 3-month-old mice had increased rates of apoptosis associated with increased cell cycling and DNA damage. Gene expression profiling of these MDS progenitors revealed a specific reduction in Bcl2. Restoration of Bcl2 expression by a BCL2 transgene blocked apoptosis of the MDS progenitors, which corrected the macrocytic anemia. Blocking apoptosis also restored cell-cycle quiescence and reduced DNA damage in the MDS progenitors. We expected that preventing apoptosis would accelerate malignant transformation to acute myeloid leukemia (AML). However, contrary to expectations, preventing apoptosis of premalignant cells abrogated transformation to AML. In contrast to the current dogma that overcoming apoptosis is an important step toward cancer, this work demonstrates that gaining a survival advantage of premalignant cells may delay or prevent leukemic progression. PMID:22855610

  4. Therapy-associated myelodysplastic syndrome with monosomy 7 arising in a Muir-Torre Syndrome patient carryingSETBP1mutation.

    Science.gov (United States)

    Ullman, David; Baumgartner, Erin; Wnukowski, Nicholas; Koenig, Gabe; Mikhail, Fady M; Pavlidakey, Peter; Peker, Deniz

    2018-02-01

    Muir-Torre Syndrome (MTS) is a rare hereditary autosomal dominant cancer syndrome and is linked to hereditary non-polyposis colorectal carcinoma (Lynch Syndrome). Individuals develop various skin neoplasms in addition to colorectal, endometrial and upper gastrointestinal malignancies. Therapy-associated myelodysplastic syndrome (T-MDS) is an aggressive hematologic malignancy and is considered a pre-leukemic phase. T-MDS is associated with prior exposure to chemo- and radiotherapy that potentially results in DNA damage. The current case report presents a 74-year-old male MTS patient with prior history of solid tumors and radiation therapy with new onset cytopenia. A subsequent bone marrow biopsy revealed multilineage dysplasia with a high blast count and a diagnosis of high grade T-MDS was rendered. FISH and G-banded karyotype analyses revealed 5q deletion and monosomy 7. This is a unique case of T-MDS arising in the setting of MTS. Secondary malignancies including MDS and acute leukemia may occur in cancer survivors and are often associated with an unfavorable prognosis. This case demonstrates the need to be aware of the risk of secondary hematologic malignancies in cancer patients and a thorough clinical and lab work-up are warranted in patients with persistent or transfusion requiring cytopenia(s).

  5. Valor prognóstico da troponina I de alta sensibilidade versus troponina T nas síndromes coronarianas agudas Prognostic value of high-sensitivity troponin I versus troponin T in acute coronary syndromes

    Directory of Open Access Journals (Sweden)

    Luis Cláudio Lemos Correia

    2012-05-01

    of high-sensitivity cardiac troponin I (hs-cTnI, compared with conventional cardiac troponin T (cTnT in the setting of non-ST elevation acute coronary syndromes. METHODS: At hospital admission, a plasma sample was collected from 103 consecutive patients with unstable angina or non-ST elevation acute myocardial infarction. In this sample, troponin was measured both by hs-cTnI and cTnT methods. Their prognostic value was compared as to the occurrence of major cardiovascular events, defined as a combination of death, nonfatal acute myocardial infarction or refractory unstable angina during hospitalization. RESULTS: During median hospitalization of 8 days (interquartile range = 5 - 11, the incidence of cardiovascular events was 10% (5 deaths, 3 non-fatal myocardial infarctions and 2 non-fatal refractory anginas. High-sensitivity troponin I significantly predicted cardiovascular events, with a C-statistics of 0.73 (95% CI = 0.59 - 0.87, similarly to cTnT (0.70; 95% CI = 0.55 - 0.84 - P = 0.75. The definition of positive cardiac marker that provided the best prognostic accuracy was hs-cTnI > 0.055 µg/L and cTnT > 0.010 µg/L, with equal sensitivity of 90% and specificity of 52% for both assays. Positive hs-cTnI was associated with 17% incidence of events, compared with 2% in patients with negative hs-cTnI (P = 0.02. CONCLUSION: High-sensitivity troponin I predicts cardiovascular events similarly to conventional troponin T in the setting of non-ST-elevation ACS. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0

  6. GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among Phenotypes Using GWAS Results.

    Science.gov (United States)

    Wei, Wei; Ramos, Paula S; Hunt, Kelly J; Wolf, Bethany J; Hardiman, Gary; Chung, Dongjun

    2016-01-01

    Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes.

  7. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12...... with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III...

  8. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated...

  9. The development of integration mobile-based home care support systems: MDS-HC as an example.

    Science.gov (United States)

    Hsiao, Fang-Ying; Kuo, Yu-Yin; Chang, Polun; Chiehwen, Ed Hsu

    2008-11-06

    The MDS-HC (Minimum Data Set for Home Care Assessment Instrument) has been an effective home care evaluation instrument. However it was not yet accepted in Taiwan because it is too long for our over-burdened home care nurses. We developed integrated mobile-based home care support system using MDS-HC. The results showed that an integration mobile-based system can increase efficiency and reduce manual work.

  10. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

    International Nuclear Information System (INIS)

    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L.

    2015-01-01

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS

  11. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L. [Department of Hematology, Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai Xuhui District Central Hospital, Shanghai (China)

    2015-01-20

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.

  12. The MDS-UPDRS Part II (motor experiences of daily living) resulted useful for assessment of disability in Parkinson's disease.

    Science.gov (United States)

    Rodriguez-Blazquez, Carmen; Rojo-Abuin, Jose Manuel; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Bergareche-Yarza, Alberto; Chade, Anabel; Garretto, Nelida; Gershanik, Oscar; Kurtis, Monica M; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Moore, Henry P; Rodriguez-Violante, Mayela; Singer, Carlos; Tilley, Barbara C; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G; Martinez-Martin, Pablo

    2013-10-01

    To evaluate the motor experiences of daily living section of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS M-EDL) for assessing disability in PD patients; to determine the association between disability and quality of life; and to identify cut-off score ranges for no, mild, moderate and severe disability with this measure. International, observational, cross-sectional study of 435 PD patients, assessed with: MDS-UPDRS, Hoehn and Yahr staging, Rapid Assessment of Disability Scale, Clinical Impression of Severity Index for PD, Parkinson's Disease Questionnaire-8 and EQ-5D. Descriptive statistics, Spearman's rank correlation coefficients, Kruskal-Wallis test for group comparisons, ordinal logistic regression analysis for setting cut-off values and a step-wise multiple linear regression model were calculated. MDS-UPDRS M-EDL correlated 0.70-0.80 with other disability measures, and -0.46 to 0.74 with quality of life scales. Scores significantly increased with higher disease duration and severity (p MDS-UPDRS nM-EDL section as the main determinant of M-EDL, followed by the rest of MDS-UPDRS sections (explained variance: 59%). MDS-UPDRS M-EDL proved to be useful for assessing disability in PD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Chromosomal instability and the abrogated G2/M arrest in x-irradiated myelodysplastic syndrome cells

    International Nuclear Information System (INIS)

    Ban, S.; Sudo, H.; Saegusa, K.; Sagara, M.; Imai, T.; Kimura, A.

    2003-01-01

    A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors in Hiroshima. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the karyotypes of bone marrow cells and the micronucleus (MN) frequency in peripheral T lymphocytes of twenty- three atomic bomb survivors with MDS and five normal individuals. Aneuploidy was observed in 10 of 23 patients. Chromosome aberrations were observed in 3 of 12 patients with mild symptoms, and six of 11 patients of severe symptoms. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation- therapy, their unusual radiosensitivity may be related to their chromosomal or genomic instability. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrest was observed in 10 of 12 MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that the abrogated G2/M arrest may be involved in the pathophysiology of disease progression and the high radiation sensitivity of patients

  14. Severe congenital neutropenia (Kostmann Syndrome) | Al-Jaouni ...

    African Journals Online (AJOL)

    However, hematopoietic stem cell transplantation has shown promise in the treatment of non-responders. About 60-80% of SCN cases are associated with constitutive mutations in one copy of the gene encoding neutrophil elastase ELA2. Myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) have been ...

  15. Allogeneic stem cell transplantation for myelodysplastic syndromes: critical for cure?

    NARCIS (Netherlands)

    Witte, T.J.M. de

    2011-01-01

    Allogeneic stem cell transplantation (SCT) is the treatment of choice for young patients (age syndromes (MDS) characterized by poor-risk or intermediate-risk cytogenetics, who have a histocompatible related or unrelated donor. For patients who lack an human

  16. Global H3K4me3 genome mapping reveals alterations of innate immunity signaling and overexpression of JMJD3 in human myelodysplastic syndrome CD34+ cells

    OpenAIRE

    Wei, Yue; Chen, Rui; Dimicoli, Sophie; Bueso-Ramos, Carlos; Neuberg, Donna; Pierce, Sherry; Wang, Hui; Yang, Hui; Jia, Yu; Zheng, Hong; Fang, Zhihong; Nguyen, Martin; Ganan-Gomez, Irene; Ebert, Benjamin; Levine, Ross

    2013-01-01

    The molecular bases of myelodysplastic syndromes (MDS) are not fully understood. Trimethylated histone 4 lysine 3 (H3K4me3) is present in promoters of actively transcribed genes and has been shown to be involved in hematopoietic differentiation. We performed a genome-wide H3K4me3 CHIP-Seq analysis of primary MDS bone marrow (BM) CD34+ cells. This resulted in the identification of 36 genes marked by distinct higher levels of promoter H3K4me3 in MDS. A majority of these genes are involved in NF...

  17. A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts.

    Science.gov (United States)

    Garcia-Manero, G; Sekeres, M A; Egyed, M; Breccia, M; Graux, C; Cavenagh, J D; Salman, H; Illes, A; Fenaux, P; DeAngelo, D J; Stauder, R; Yee, K; Zhu, N; Lee, J-H; Valcarcel, D; MacWhannell, A; Borbenyi, Z; Gazi, L; Acharyya, S; Ide, S; Marker, M; Ottmann, O G

    2017-12-01

    Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m 2 . More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.

  18. Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients.

    Science.gov (United States)

    Skorvanek, Matej; Martinez-Martin, Pablo; Kovacs, Norbert; Zezula, Ivan; Rodriguez-Violante, Mayela; Corvol, Jean-Christophe; Taba, Pille; Seppi, Klaus; Levin, Oleg; Schrag, Anette; Aviles-Olmos, Iciar; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Aschermann, Zsuzsanna; Benchetrit, Eve; Benoit, Charline; Bergareche-Yarza, Alberto; Cervantes-Arriaga, Amin; Chade, Anabel; Cormier, Florence; Datieva, Veronika; Gallagher, David A; Garretto, Nelida; Gdovinova, Zuzana; Gershanik, Oscar; Grofik, Milan; Han, Vladimir; Kadastik-Eerme, Liis; Kurtis, Monica M; Mangone, Graziella; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Minar, Michal; Moore, Henry P; Muldmaa, Mari; Mueller, Christoph; Pinter, Bernadette; Poewe, Werner; Rallmann, Karin; Reiter, Eva; Rodriguez-Blazquez, Carmen; Singer, Carlos; Valkovic, Peter; Goetz, Christopher G; Stebbins, Glenn T

    2018-03-28

    The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients. We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items. A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue. This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD. Copyright © 2018. Published by Elsevier Ltd.

  19. Relationship between the MDS-UPDRS domains and the health-related quality of life of Parkinson's disease patients.

    Science.gov (United States)

    Martínez-Martín, P; Rodríguez-Blázquez, C; Forjaz, M J; Alvarez-Sánchez, M; Arakaki, T; Bergareche-Yarza, A; Chade, A; Garretto, N; Gershanik, O; Kurtis, M M; Martínez-Castrillo, J C; Mendoza-Rodríguez, A; Moore, H P; Rodríguez-Violante, M; Singer, C; Tilley, B C; Huang, J; Stebbins, G T; Goetz, C G

    2014-03-01

    The Movement Disorder Society sponsored version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive instrument for assessing Parkinson's disease (PD). The present study was aimed at determining the relationships between MDS-UPDRS components and health-related quality of life (HRQoL) evaluations in PD patients. An international, multicenter, cross-sectional study was carried out of 435 PD patients assessed with the MDS-UPDRS, Hoehn and Yahr (HY), Clinical Impression Severity for PD, EQ-5D and PD Questionnaire - eight items (PDQ-8). Spearman's rank correlation coefficients, exploratory factor analysis and multiple linear regression models (dependent variables EQ-5D and PDQ-8) were performed. The participants' age was 66.71 ± 10.32 years (51.5% men). PD duration was 8.52 ± 6.14, and median HY was 2 (range 1-5). The correlation between the EQ-5D index and the MDS-UPDRS ranged from -0.46 (Part IV) to -0.72 (Part II) and for the PDQ-8 index from 0.47 (Part III) to 0.74 (Part II). In multiple regression models with the MDS-UPDRS domains as independent variables, the main determinant for both the EQ-5D index and the PDQ-8 was Part II followed by Part I. After factorial grouping of the cardinal PD manifestations embedded in the MDS-UPDRS Parts III and IV for inclusion into multiple regression models, a factor formed by M-EDL, nM-EDL and fluctuations was the main determinant for both the EQ-5D and PDQ-8 indexes. The MDS-UPDRS component most tightly related with the HRQoL measures was a combination of motor and non-motor experiences of daily living. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  20. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Atwal, Paldeep S; Macmurdo, C

    2015-12-01

    Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1-associated lissencephaly) include classic lissencephaly, microcephaly, cardiac malformations, growth restriction, and characteristic facial changes. Individuals with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome) are known to have congenital cardiac malformations (in particular conotruncal defects), palatal abnormalities (especially velopharyngeal insufficiency), hypocalcemia, immune deficiency, learning disabilities, and characteristic facial features. This case report describes phenotypic characteristics of a patient with extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is unique in the medical literature. Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period.

  1. Cognitive distortions based on MDS configuration and sketch mapping: a case study in Beijing

    Science.gov (United States)

    Shen, Si; Xue, Lulu; Wu, Lun; Liu, Yu

    2007-06-01

    As an emerging field, cognitive map kept playing a significant role in geography these decades. To date, there are two dominant methods to externalize human's internal cognitive map, namely, multidimensional scaling (MDS) and skech mapping. However, among most recent researches on cognitive map, the differences between both methods are always ignored. The usage of one method over another is still under scrutiny. In order to shed light on the similarity or distinctions of MDS configuration and sketch mapping, we conducted an experiment on Beijing residents by requesting a sketch of the region within 3rd Ring and meanwhile extracting distance estimates between 8 landmarks. Employing the Bidimensional regression along with standard deviational ellipse, we studied the global and local distortions among two kinds of cognitive maps and quantitatively measure the overall and local cognitive maps distortions. Besides, we use Monte Carlo simulation method to calculate the radius of distortion for the Distortion Index (DI). It shows that the average cognitive distortion of habitants in Beijing is 2km to 3km, and the distortion takes 2nd-ring road as a border, displaying a southwest-northeast diagonal stretch and an east-west contracted tendency. The distortion in the two methods is remarkably both correlated with factors, such as travel frequency and years of residence. Comparing two methods, it turned out that sketch map was more consistent with real map, while the distortion orientations of sketch map resembled MDS configuration. Finally, we gave possible reasons with regard to above conclusions and advices for future usage of two methods.

  2. Prune belly syndrome with pouch colon with scaphoid megalourethra

    African Journals Online (AJOL)

    We here report a rare association of megalourethra with pouch colon with prune belly syndrome. We also provide a newer embryological and prognostic perspective to this association. Keywords: megalourethra, prune belly syndrome pouch colon, scaphoid ...

  3. The DVB Channel Coding Application Using the DSP Development Board MDS TM-13 IREF

    Directory of Open Access Journals (Sweden)

    M. Slanina

    2004-12-01

    Full Text Available The paper deals with the implementation of the channel codingaccording to DVB standard on DSP development board MDS TM-13 IREF andPC. The board is based on Philips Nexperia media processor andintegrates hardware video ADC and DAC. The program libraries featuresused for MPEG based video compression are outlined and then thealgorithms of channel decoding (FEC protection against errors arepresented including the flowchart diagrams. The paper presents thepartial hardware implementation of the simulation system that coversselected phenomena of DVB baseband processing and it is used for realtime interactive demonstration of error protection influence ontransmitted digital video in laboratory and education.

  4. Differential diagnosis of myelodysplastic syndrome and aplastic anemia using MRI

    International Nuclear Information System (INIS)

    Jung, Seung Eun; Park, Jung Mi; Lee, Jae Mun; Kim, Ki Tae; Kim, Dong Wook; Kim, Chun Choo; Kim, Chun Yul; Shinn, Kyung Sub

    1995-01-01

    To assess the patterns of myelodysplastic syndrome (MDS) and aplastic anemia (AA) on MRI of the spinal bone marrow and to find the differential points between the two groups. Fourteen patients with MDS (n=7) and AA (n=7) were studied using magnetic resonance imaging. Sagittal images from the lower thoracic and lumbar vertebral marrow were evaluated on T1-weighted and STIR images. Five distinct patterns of signal intensity of the T1-weighted and STIR images were classified. T1 and T2 relaxation times and T1 marrow/fat signal intensity ratio were measured and analyzed (t-test). The cellularity of bone marrow was evaluated on histologic slides. MDS showed homogeneously low signal intensity on T1WI and high signal intensity on STIR image, indicating hypercellular marrow, whereas AA showed relative high signal intensity on T1WI and low signal intensity on STIR image, representing fatty marrow. T1 and T2 relaxation time (T1 for MDS=750.26 msec ± 177.50, T1 for AA=413.21 msec ± 167.39 (ρ < 0.000), T2 for MDS=91.86 msec ± 14.16, T2 for AA=81.44 msec ± 15.31 (ρ < 0.001) and T1 marrow/fat signal intensity ratio (0.22 ± 0.048 in MDS, 0.30 ± 0.083 in AA (ρ < 0.000) revealed statistically significant difference between the two groups. Although the marrow aspiration and needle biopsy are mandatory in hematologic disease for diagnosis, there are limited in assessing the change of total marrow mass. Therefore MRI of bone marrow might be useful in distinguishing MDS from AA because of its ability of representation of total marrow mass

  5. Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier

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    Qiang Li

    2017-01-01

    Full Text Available Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS and support vector machine (SVM algorithms in a quartz crystal microbalance (QCM-based electronic nose (e-nose we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3% showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN classifier (93.3% and moving average-linear discriminant analysis (MA-LDA classifier (87.6%. The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

  6. Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier.

    Science.gov (United States)

    Li, Qiang; Gu, Yu; Jia, Jing

    2017-01-30

    Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS) and support vector machine (SVM) algorithms in a quartz crystal microbalance (QCM)-based electronic nose (e-nose) we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3%) showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN) classifier (93.3%) and moving average-linear discriminant analysis (MA-LDA) classifier (87.6%). The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization) performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

  7. [Expression of autophagy related gene BECLIN-1 and number of autophagic vacuoles in bone marrow mononuclear cells from 40 myelodysplastic syndromes patients and their significance].

    Science.gov (United States)

    Hu, Bin; Yue, Qin-Fang; Chen, Ye; Bu, Fan-Dan; Sun, Chun-Yan; Liu, Xin-Yue

    2015-02-01

    The purpose of this study was to detect the expression level of autophagy related gene BECLIN-1 and the number of autophagic vacuoles in bone marrow mononuclear cells (BMMNC) from myelodysplastic syndrome(MDS) patients and to explore their difference in different stage of MDS and relationship between their difference and disease characteristics. The BMMNC from 9 normal controls, 19 cases of low-risk MDS, 14 cases of high-risk MDS and 7 cases of MDS-transformed AML were collected. The expression level of BECLIN-1 was detected by real time PCR (RT-PCR) and the amount of autophagic vacuoles was counted by transmission electron microscopy. The expression level of BECLIN-1 in BMMNC from patients with low-risk group was obviously higher than that in BMMNC from normal controls; the expression level of BECLIN-1 in BMMNC from patients of hgh risk group was higher than that in BMMNC of normal group, but there was no statistical significance (P > 0.05); the expression level of BECLIN-1 in BMMNC from patients with MDS-transformed AML group was significanly lower than that in BMMNC of normal group (P vacuoles in BMMNC from patients with low-risk and high-risk MDS groups was more than that in normal control, but there was no stetistcal significance (P > 0.05), while the amount of autopuagic vecuoles in BMMNC from patients of MDS-transformed AML group was significantly less (P vacuoles in BMMNC from patients with MDS progression and patients with MDS-transformed AML are gradually declining. The autophagy may be associated with disease progression.

  8. An Unexpected Innocent Complication Associated with Azacitidine Treatment of Myelodysplastic Syndrome: Erythema Annulare Centrifugum

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    Esra Turan Erkek

    2016-03-01

    Full Text Available Skin lesions accompanying hematological malignancies can be formed due to either direct tumor infiltration of the skin or indirect effects. Indirectly developing lesions may be a component of paraneoplastic syndrome. Erythema annulare centrifugum (EAC is considered to be a hypersensitivity reaction developed against various antigens associated with infections, drugs, and endocrine diseases. EAC, rarely seen in neoplastic diseases, has been reported in lymphoma, leukemia, histiocytosis, and prostate cancer. Here we report EAC in a patient using a hypomethylating agent, azacitidine. A 69-year-old female patient was admitted to our polyclinic with weakness and ecchymosis in her legs existing for 3 months. She was considered as having refractory anemia with excess blasts-2 according to myelodysplastic syndrome (MDS classification [1]. Because there was only hyperdiploidy in conventional cytogenetic examination, she was classified in group intermediate-2 of the International Prognostic Scoring System. She had a history of radical mastectomy and adjuvant chemoradiotherapy for breast cancer 3 years ago. She said that variously sized round and oval erythematous, itching, painless lesions had formed in the abdominal region on the 4th day of azacitidine usage (75 mg/m2/day, 7 days, s.c. (Figure 1 and 2. There were no concomitant complaints or physical examination findings except fatigue. After azacitidine was stopped, a skin biopsy was taken. In the biopsy, mild perivascular inflammatory infiltration accompanying vascular ectasia in the papillary dermis was detected. The possibility of paraneoplastic syndrome was excluded due to the disappearance of all lesions by 1 week after cessation of treatment. During the second course of azacitidine, the lesions reoccurred on the second day. Subsequently to the second course, the patient died of sepsis, which developed after pneumonia.

  9. [Comparison of chromosome karyotype between myelodysplastic syndrome and acute leukemia patients confirmed at the same period].

    Science.gov (United States)

    Jiang, Ming; Wen, Bing-Zhao; Li, Ling; Chen, Shuang; Cheng, Hong; Hao, Jian-Ping; Chen, Rong; Wang, Lei; Zhao, Fang

    2014-04-01

    This study was purposed to compare and analyze the relationship between the abnormality of chromosome karyotypes and diagnosis, prognosis of MDS and AML patients, as well as to explore the characteristics of chromosome prognostic stratification in MDS and AML patients of different ages. The cytogenetic karyotype analysis was performed in 134 cases of MDS and 123 cases of AML by using bone marrow short-term culture and R-banding technique. The results indicated that the detected rates of chromosome abnormal karyotypes in MDS and AML patients were 41% and 61% respectively. The abnormal karyotype analysis of MDS and AML group showed that the abnormal karyotype in MDS group displayed number abnormality as the dominate (mainly the +8), while the abnormal karyotype in AML group displayed structure abnormality as the dominant [mainly, t(15;17) and t(8;21)]. The detected abnormal karyotype are mainly for the +8 which has ambiguous correlation with FAB subtype; the detection rates of complex karyotype abnormalities, favourable prognosis karyotype as well as poor prognosis karyotype in the MDS group obviously higher than that of AML group. Among patients with MDS transformed into AML, 12 cases had chromosome abnormal karyotype. There were 3 cases of chromosome abnormal karyotype in AML group which were transformed by MDS. The analysis of age stratification between two groups showed that the detected rate of abnormal karyotype was enhanced with the increase of age in MDS group, and detected rate in ≥ 60 years old group was obviously higher than that in patients with ≤ 30 age group.The detected rate of complex karyotype abnormalities in three age groups of MDS did not show statistical difference; the detected rate of abnormal karyotype in AML group decreased with the increase of age, the detected rate in ≤ 30 years old group was obviously higher than that in ≥ 60 age group,while the detection rate of complex karyotype abnormalities showed that the detected rate in

  10. Radiotherapy- and chemotherapy-induced myelodysplasia syndrome: a nationwide population-based nested case-control study.

    Science.gov (United States)

    Sun, Li-Min; Lin, Cheng-Li; Lin, Ming-Chia; Liang, Ji-An; Kao, Chia-Hung

    2015-05-01

    This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT).We performed a nested case-control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33-1.77; CT: OR = 1.51; 95% CI = 1.25-1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details.This population-based nested case-control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used.

  11. Prognostic markers of canine pyometra

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    M.C. Sant'Anna

    2014-12-01

    Full Text Available The pyometra is a disease that affects middle age and elderly female dogs during diestrus. Hormonal, microbiological, biochemical and hematological aspects are well described. However, few studies have evaluated the role of each in the prognosis of canine pyometra. The aim of this study was to identify markers associated with clinical worsening of dogs with pyometra. We prospectively evaluated 80 dogs with pyometra treated surgically. Group 1 consisted of dogs that were discharged within 48 hours after surgery and Group 2 consisted of those who required prolonged hospitalization or died. The findings of hematological, biochemical and blood lactate levels were compared between groups and variables such as bacterial multidrug resistance, systemic inflammatory response syndrome (SIRS, hyperlactatemia and increased creatinine were analyzed through the dispersion of frequencies between groups. Among the variables studied, the presence of SIRS and elevated serum creatinine >2.5mg/mL were effective in predicting the worsening of the disease and can be used as prognostic markers of canine pyometra.

  12. On Orbit Osteobiology Experiments: from "STROMA" to "MDS" -from in vitro to in vivo

    Science.gov (United States)

    Liu, Yi; Cancedda, Ranieri

    Spaceflight causes profound changes in the skeleton, in particular, in the weight-loading bones. Uncoupling of bone remodeling equilibrium between bone formation and resorption is con-sidered responsible for the microgravity-induced bone loss. These changes result in weak-ened and brittle bones prone to fracture on re-entry and in accelerated osteoporosis, making bone deterioration a major problem obstructing the prospects of long-duration manned space flight. Osteoblasts (bone forming cells) and osteocytes (bone resorption cells) are known to be mechano-sensors. Short-exposure of osteoblasts to simulated microgravity ensnarled cell adhe-sion and cytoskeleton. Also osteoblast precursors such as bone marrow stroma cells (BMSC) were shown to be sensitive to mechanical loading. We performed a series of STROMA space-flight experiments by culturing BMSC or co-culturing osteoblasts and osteoclast precursors in automated bioreactors on orbit. Genechip analysis revealed an inhibition of cell proliferation and an unexpected activation of nervous system development genes by spaceflight. To unravel effects of microgravity on genes governing bone mass, transgenic mice with a higher bone mass were flown to orbit inside the Mice Drawer System (MDS) payload. The MDS experiment was launched inside Shuttle Discovery in STS-128 on August 28 2009 at 23:58 EST, and returned to earth by Shuttle Atlantis in STS129 on November 27 2009 at 9:47 EST, marking it as the first long duration animal experiment on the International Space Station (ISS).

  13. Wormhole Detection Based on Ordinal MDS Using RTT in Wireless Sensor Network

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    Saswati Mukherjee

    2016-01-01

    Full Text Available In wireless communication, wormhole attack is a crucial threat that deteriorates the normal functionality of the network. Invasion of wormholes destroys the network topology completely. However, most of the existing solutions require special hardware or synchronized clock or long processing time to defend against long path wormhole attacks. In this work, we propose a wormhole detection method using range-based topology comparison that exploits the local neighbourhood subgraph. The Round Trip Time (RTT for each node pair is gathered to generate neighbour information. Then, the network is reconstructed by ordinal Multidimensional Scaling (MDS followed by a suspicion phase that enlists the suspected wormholes based on the spatial reconstruction. Iterative computation of MDS helps to visualize the topology changes and can localize the potential wormholes. Finally, a verification phase is used to remove falsely accused nodes and identify real adversaries. The novelty of our algorithm is that it can detect both short path and long path wormhole links. Extensive simulations are executed to demonstrate the efficacy of our approach compared to existing ones.

  14. Distinct neutrophil subpopulations phenotype by flow cytometry in myelodysplastic syndromes.

    Science.gov (United States)

    Vikentiou, Myrofora; Psarra, Katerina; Kapsimali, Violetta; Liapis, Konstantinos; Michael, Michalis; Tsionos, Konstantinos; Lianidou, Evi; Papasteriades, Chryssa

    2009-03-01

    The cardinal feature of myelodysplastic syndromes (MDS) is dysplasia involving one or more myeloid cell lineages. In the present study, we used 4-color flow cytometric analysis to investigate dysgranulopoiesis in bone marrow specimens from 65 patients with MDS. The antigen expression patterns of total neutrophil granulocytes (TNG) and of the two distinct neutrophil granulocytic subpopulations (NGSs), NGS-1 (dimmer CD45 expression) and NGS-2 (stronger CD45 expression) identified on the side scatter (SS) vs. CD45-intensity plot, were studied. The neutrophil granulocytes from patients with MDS showed characteristic antigen expression aberrancies which were more pronounced in NGS-2 subpopulation. Studying separately the NGS-2 subpopulation with the CD16/MPO/LF combination, the low CD16(+)/MPO(+) and low CD16(+)/LF(+) percentages seemed to discriminate between lower-risk and higher-risk patients with MDS in most occasions. Furthermore, a detailed assessment of the NGS-1 and NGS-2 immunophenotypic patterns revealed early dysplastic changes, not otherwise observed by standard TNG analysis, especially in cases of lower-risk MDS.

  15. Combined stratification of refractory anemia according to both WHO and IPSS criteria has a prognostic impact and improves identification of patients who may benefit from stem cell transplantation.

    Science.gov (United States)

    Cermák, Jaroslav; Vítek, Antonín; Michalová, Kyra

    2004-06-01

    A retrospective analysis of the relationship between the initial classification according to either FAB or WHO criteria, the presence of risk factors and the type of therapy including stem cell transplantation (SCT) on the survival was performed in a group of 106 patients with primary myelodysplastic syndrome (MDS) of FAB RA subtype. Allogeneic SCT early in the course of the disease did not significantly affect median survival in RA patients evaluated either according to FAB criteria (63.2 months in 17 SCT patients versus 64.4 months in 89 non-transplanted (non-SCT) patients) or in subgroups classified separately according to WHO (64.0 months in SCT versus 91.0 months in non-SCT RA patients and 66.2 months in SCT versus 43.0 months in non-SCT refractory cytopenia with multilineage dysplasia (RCMD) patients) or International Prognostic Scoring System (IPSS) criteria despite decreased incidence of leukemic transformation (5% in SCT versus 32% in non-SCT patients). Neither univariate or multivariate analysis of different clinical and laboratory parameters revealed a significant effect of SCT on 3 or 5 years survival in RA patients. The most probable explanation was a relatively high rate of transplantation related mortality (41%) on one hand together with a slow disease progression towards leukemia (24% at 5 years in non-SCT) on the other hand. A more refined stratification of patients based on the combined WHO morphology classification and IPSS cytogenetic criteria revealed subgroup of 11 non-SCT patients with RCMD and poor karyotype with median survival significantly different from that in five SCT patients (9.2 months in non-SCT versus 89.3 months in SCT, P=0.05). Thus, combined WHO morphology/IPSS cytogenetics criteria may be helpful for identification of the high risk patients with the RA group who may benefit from early SCT despite the relatively high incidence of SCT-related complications.

  16. Determinantes prognósticos em pacientes com síndrome coronariana aguda sem elevação do segmento ST Prognostic factors in patients with acute coronary syndrome without ST segment elevation

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    Jessica Carolina Matos D'Almeida Santos

    2013-05-01

    Full Text Available FUNDAMENTO: Em pacientes com Síndromes Coronarianas Agudas (SCA sem Supradesnivelamento do Segmento ST (SST, sugere-se que uma série de marcadores (células inflamatórias, hiperglicemia e função renal é capaz de identificar indivíduos com maior risco para eventos cardiovasculares. OBJETIVO: Avaliar o impacto desses parâmetros laboratoriais em desfechos intra-hospitalares de pacientes com SCA sem SST. MÉTODOS: Foram avaliados prospectivamente 195 pacientes admitidos consecutivamente com SCA sem SST. Foram registrados dados clínicos, demográficos e laboratoriais ao longo do período de internação no hospital, em relação à ocorrência ou não de eventos combinados. RESULTADOS: A idade média foi de 67 ± 12 anos, e 52% eram homens. Na análise da área sob a curva ROC, somente a razão neutrófilo/linfócito (AUC: 70%, IC95%: 56%-82%, p = 0,006 e a creatinina (AUC: 62%, IC95%: 50%-80%, p = 0,03 discriminaram aqueles pacientes com SCA sem SST que apresentaram algum desfecho. Os pacientes que sofreram algum evento adverso durante a internação apresentaram menores contagens de linfócitos (1502 ± 731 / mm³ vs. 2020 ± 862 / mm³; p = 0,002, menores taxas de filtração glomerular (51 ± 27 mL/min vs. 77±34 mL/min; p BACKGROUND: In patients with acute coronary syndromes (ACS without ST segment elevation (SSE, it is suggested that a series of markers (inflammatory cells, hyperglycemia and renal function can identify individuals with increased risk for cardiovascular events. OBJECTIVE: To evaluate the impact of these laboratory parameters on intra-hospital outcomes of patients with ACS with no SSE. METHODS: We prospectively evaluated 195 patients consecutively admitted with ACS with no SSE. Demographic and clinical laboratory data were recorded during the course of the hospitalization period in relation to the occurrence of combined events. RESULTS: Mean age was 67 ± 12 years, and 52% were men. In analyzing the area under the ROC

  17. Conventional and molecular cytogenetic features of myelodysplastic syndrome in China.

    Science.gov (United States)

    Chen, L- J; Li, J- Y; Zhu, Y; Qiu, H- R; Pan, J- L; Wang, R; Qian, S- X; Xu, W; Xue, Y- Q

    2007-12-01

    Myelodysplastic syndrome (MDS) constitutes a heterogeneous group of hematopoietic stem cell disorder characterized by peripheral blood cytopenia(s), in the presence of hypercellular bone marrow with features of ineffective hematopoiesis, and susceptibility to acute leukemia (AL). Although the precise pathogenesis of MDS remains to be clarified, cytogenetic abnormalities seem to be involved in its pathogenesis and are considered as an important factor in diagnosis and predicting clinical outcome. To explore the cytogenetic features of Chinese patients with myelodysplastic syndrome (MDS). Conventional cytogenetic analysis was performed in 88 MDS patients and among them, 34 cases were studied by interphase fluorescence in situ hybridization (I-FISH) with precisely chromosome 8 centromere specific DNA probe and DNA specific probes for 7q32 , 5q31. Of the 88 patients, 45 (51.1%) showed clonal karyotypic abnormalities by CC at diagnosis, including numerical changes (18 cases, 20.5%), structural changes (12 cases, 13.6%), and numerical and structural changes simultaneously(15 cases, 17.0%). Trisomy 8, -5/5q-, and -7/ 7q- account for 20.5%, 15.9%, and 5.7% respectively. Complex karyotypes were observed in 17 patients, the incidence being 19.3% in the whole series of cases. Among 34 MDS patients studied by I-FISH, -5/5q-, -7/7q- and trisomy 8 occurring in 4, 2 and 10 cases respectively for CC were confirmed by I-FISH. 5 cases in 30 cases who did not show -5/5q- by CC displayed this abnormality by I-FISH. 3 cases without -7/7q- by CC presented this aberration by I-FISH. 5 cases with trisomy 8 for I-FISH was not identified this change by CC. The frequent abnormalities are trisomy 8, -5/5q- and -7/ 7q-. FISH is very useful in detecting these alterations in MDS and it is an important complement to CC.

  18. NUP98-HOX translocations lead to myelodysplastic syndrome in mice and men.

    Science.gov (United States)

    Slape, Christopher; Lin, Ying Wei; Hartung, Helge; Zhang, Zhenhua; Wolff, Linda; Aplan, Peter D

    2008-01-01

    The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplasia, and a propensity for transformation to acute myeloid leukemia (AML). A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene, most commonly leading to fusions of NUP98 with abd-b group HOX genes, including HOXD13. We used vav regulatory elements to direct expression of a NUP98-HOXD13 (NHD13) fusion gene in hematopoietic tissues. NHD13 transgenic mice faithfully recapitulate all the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia and apoptosis, and transformation to acute leukemia. The MDS that develops in NHD13 transgenic mice is highly lethal; within 14 months, 90% of the mice died of either leukemic transformation or severe anemia and leukopenia due to progressive MDS. These mice provide a preclinical model that can be used for the evaluation of MDS therapy and biology.

  19. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

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    Sílvia Saumell

    Full Text Available Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8 can be found as a constitutional mosaicism (cT8M. We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH. In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

  20. Prognostic Analysis of the Tactical Quiet Generator

    Energy Technology Data Exchange (ETDEWEB)

    Hively, Lee M [ORNL

    2008-09-01

    The U.S. Army needs prognostic analysis of mission-critical equipment to enable condition-based maintenance before failure. ORNL has developed and patented prognostic technology that quantifies condition change from noisy, multi-channel, time-serial data. This report describes an initial application of ORNL's prognostic technology to the Army's Tactical Quiet Generator (TQG), which is designed to operate continuously at 10 kW. Less-than-full power operation causes unburned fuel to accumulate on internal components, thereby degrading operation and eventually leading to failure. The first objective of this work was identification of easily-acquired, process-indicative data. Two types of appropriate data were identified, namely output-electrical current and voltage, plus tri-axial acceleration (vibration). The second objective of this work was data quality analysis to avoid the garbage-in-garbage-out syndrome. Quality analysis identified more than 10% of the current data as having consecutive values that are constant, or that saturate at an extreme value. Consequently, the electrical data were not analyzed further. The third objective was condition-change analysis to indicate operational stress under non-ideal operation and machine degradation in proportion to the operational stress. Application of ORNL's novel phase-space dissimilarity measures to the vibration power quantified the rising operational stress in direct proportion to the less-than-full-load power. We conclude that ORNL's technology is an excellent candidate to meet the U.S. Army's need for equipment prognostication.

  1. Síndromes mielodisplásicas e mielodisplásicas/mieloproliferativas Myelodysplastic syndromes and diseases with myelodysplastic and myeloproliferative features

    Directory of Open Access Journals (Sweden)

    José Vassallo

    2009-08-01

    Full Text Available As síndromes mielodisplásicas (SMD representam um grupo heterogêneo de doenças hematológicas caracterizadas por hematopoese ineficaz e risco aumentado de evolução para leucemia mieloide aguda. Neste artigo educativo são apresentados aspectos gerais da sua fisiopatologia, diagnóstico, apresentação histopatológica e seu papel no diagnóstico diferencial, classificação e estratificação prognóstica. Ressalta-se a importância da avaliação clínica e laboratorial, que inclui avaliação do sangue periférico e medula óssea: morfologia - aspirado medular e biópsia óssea -, citogenética, imunofenotipagem, além de dados evolutivos. O diagnóstico definitivo, em especial nos casos de baixo risco, deve considerar a exclusão de causas não clonais que podem, através de alterações dismielopoéticas reativas, simular a mielodisplasia, tais como infecções virais, principalmente pelo HIV. A nova classificação revisada da Organização Mundial da Saúde (OMS-2008 é apresentada e discutida.Myelodysplastic syndromes (MDS represent a heterogeneous group of hematologic disorders characterized by ineffective hematopoiesis and an increased risk of developing acute myeloid leukemia. In this educational article the general aspects of the physiopathology, diagnosis, and histopathological features of MDS and their role in differential diagnosis, classification and prognostic categorization are presented. The importance of clinical and laboratory evaluations, including peripheral blood and bone marrow analyses, including morphology - aspirate and core biopsy, cytogenetics, immunophenotype and careful serial follow-up is emphasized. Definite diagnosis of MDS, especially in low-risk subtypes, should consider the exclusion of disorders with reactive bone marrow alterations, such as viral infections for example HIV. The new revised World Health Organization (WHO-2008 classification is presented and discussed.

  2. Prognostic factors for medulloblastoma

    International Nuclear Information System (INIS)

    Jenkin, Derek; Al Shabanah, Mohamed; Al Shail, Essam; Gray, Alan; Hassounah, Maher; Khafaga, Yasser; Kofide, Amani; Mustafa, Mahmoud; Schultz, Henrik

    2000-01-01

    Purpose: To evaluate prognostic factors for medulloblastoma. Methods and Materials: One hundred and seventy-three consecutive patients with medulloblastoma, treated at King Faisal Specialist Hospital (KFSH) from 1988-1997, were reviewed. Eighty-four percent were children less than 15 years old. From 1988-1994, treatment was at the discretion of the investigator. From 1994-1998, patients entered a single-arm best practice protocol in which, in staged patients, the surgical intent was total resection, standard radiation treatment was defined, and adjuvant chemotherapy was given to a 'high-risk' subset. Results: For 150 patients who completed surgical and radiation treatment, the 5-year survival rate was 58%, compared with 0% for 16 patients who were unable to start or complete radiation treatment. For staged patients, the 5-year survival was M0 + M1, 78% and M2 + M3, 21% (p 14 years and gross cystic/necrotic features in the primary tumor. The size of the primary tumor, the degree of hydrocephalus at diagnosis, the presence of residual tumor in the post-operative CT/MRI, and the functional status of the patient prior to radiation treatment were not significant factors. Conclusions: Stage M0 + M1 was the most powerful favorable prognostic factor. In Saudi Arabia more patients present with advanced disseminated disease, 41% M2 + M3, than in the West, and this impacts adversely on overall survival. Total resection and standard radiation treatment were not sensitive prognostic factors in a treatment environment in which 78% of patients underwent at least 90% tumor resection and 60% received standard radiation treatment. In order to improve the proportion of patients able to complete radiation treatment, consideration should be given to limiting resection when the attainment of total resection is likely to be morbid, and to delaying rather than omitting radiation treatment in the patient severely compromised postoperatively

  3. Additive Construction with Mobile Emplacement (ACME) / Automated Construction of Expeditionary Structures (ACES) Materials Delivery System (MDS)

    Science.gov (United States)

    Mueller, R. P.; Townsend, I. I.; Tamasy, G. J.; Evers, C. J.; Sibille, L. J.; Edmunson, J. E.; Fiske, M. R.; Fikes, J. C.; Case, M.

    2018-01-01

    The purpose of the Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) project is to incorporate the Liquid Goods Delivery System (LGDS) into the Dry Goods Delivery System (DGDS) structure to create an integrated and automated Materials Delivery System (MDS) for 3D printing structures with ordinary Portland cement (OPC) concrete. ACES 3 is a prototype for 3-D printing barracks for soldiers in forward bases, here on Earth. The LGDS supports ACES 3 by storing liquid materials, mixing recipe batches of liquid materials, and working with the Dry Goods Feed System (DGFS) previously developed for ACES 2, combining the materials that are eventually extruded out of the print nozzle. Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) is a project led by the US Army Corps of Engineers (USACE) and supported by NASA. The equivalent 3D printing system for construction in space is designated Additive Construction with Mobile Emplacement (ACME) by NASA.

  4. Wheat Mds-1 encodes a heat-shock protein and governs susceptibility towards the Hessian fly gall midge

    Science.gov (United States)

    Plant pests including insects must manipulate plants in order to utilize the nutrition and environment of the host. Here, we show that the heat-shock protein gene Mayetiola destructor susceptibility gene-1 (Mds-1) is a major susceptibility gene in wheat that allows the gall midge M. destructor, com...

  5. Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations

    DEFF Research Database (Denmark)

    Aslan, Derya; Garde, Christian; Nygaard, Mette Katrine

    2016-01-01

    Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post tra......- and metabolic pathways. Our data indicate that spliceosome mutations may play an important role in MDS pathophysiology by affecting the expression of tumor suppressor miRNA genes involved in the development and progression of MDS.......Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post...... transcriptional gene regulation. The aim of this study was to analyze the impact of spliceosome mutations on the expression of miRNAs in a cohort of 34 MDS patients. In total, the expression of 76 miRNAs, including mirtrons and splice site overlapping miRNAs, was accurately quantified using reverse transcriptase...

  6. Isotopes and innovation: MDS Nordion's first fifty years, 1946-1996

    Energy Technology Data Exchange (ETDEWEB)

    Litt, P

    2000-07-01

    Few people realize that Canada leads in the world in the production of radio isotopes, the raw material of nuclear medicine and high-tech scanners, and in their use in medicine and industry. In Isotopes and Innovation the author gives an in-depth look at MDS Nordion, a company that started as the radium sales department of Eldorado Mining and Refining, the Canadian uranium producer that was a key strategic resource for the Allies during the race to build the nuclear bomb, and went on to become the world?s leading producer of radioisotopes. When radium began to be used as a cancer treatment, Eldorado quickly became familiar with the medical marketplace and adept at developing products that could solve clinical problems and, more important, save lives. When Canadian nuclear reactors at Chalk River began producing radioisotopes that outperformed radium, Eldorado's radium sales department was transferred to a new crown corporation, Atomic Energy of Canada Limited, created to manage Canada's nuclear research establishment. The new company developed many useful applications for radioisotopes, including cobalt-60 cancer therapy machines and industrial sterilization plants. Bought by Medical Data Services Inc. in the early 1990s, MDS Nordion was a runaway success, creator and sole proprietor of several market-leading products. Isotopes and Innovation describes how a company capitalized on the byproducts of Canada's unique nuclear research program to attain a commanding international position in extremely specialized and demanding high-tech markets, a saga in which innovative research and enterprising global marketing have brought commercial success and saved countless lives around the world.

  7. Isotopes and innovation: MDS Nordion's first fifty years, 1946-1996

    International Nuclear Information System (INIS)

    Litt, P.

    2000-01-01

    Few people realize that Canada leads in the world in the production of radio isotopes, the raw material of nuclear medicine and high-tech scanners, and in their use in medicine and industry. In Isotopes and Innovation the author gives an in-depth look at MDS Nordion, a company that started as the radium sales department of Eldorado Mining and Refining, the Canadian uranium producer that was a key strategic resource for the Allies during the race to build the nuclear bomb, and went on to become the world?s leading producer of radioisotopes. When radium began to be used as a cancer treatment, Eldorado quickly became familiar with the medical marketplace and adept at developing products that could solve clinical problems and, more important, save lives. When Canadian nuclear reactors at Chalk River began producing radioisotopes that outperformed radium, Eldorado's radium sales department was transferred to a new crown corporation, Atomic Energy of Canada Limited, created to manage Canada's nuclear research establishment. The new company developed many useful applications for radioisotopes, including cobalt-60 cancer therapy machines and industrial sterilization plants. Bought by Medical Data Services Inc. in the early 1990s, MDS Nordion was a runaway success, creator and sole proprietor of several market-leading products. Isotopes and Innovation describes how a company capitalized on the byproducts of Canada's unique nuclear research program to attain a commanding international position in extremely specialized and demanding high-tech markets, a saga in which innovative research and enterprising global marketing have brought commercial success and saved countless lives around the world

  8. The biology of myelodysplastic syndromes: unity despite heterogeneity

    Directory of Open Access Journals (Sweden)

    Azra Raza

    2010-06-01

    Full Text Available Myelodysplastic syndromes (MDS traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases.

  9. First Cytogenetic Profile of Omani Patients with de novo Myelodysplastic Syndromes : Comparison with data from Asia, Africa, Europe and North and South America

    Directory of Open Access Journals (Sweden)

    Achandira M. Udayakumar

    2017-08-01

    Full Text Available Clonal cytogenetic abnormalities have been reported among 30–80% of patients with myelodysplastic syndromes (MDS; however, 20–70% of patients with MDS show a normal karyotype that may nevertheless harbour a cryptic genetic alteration. Earlier reports have suggested that the distribution of specific chromosomal aberrations varies among Western and Asian countries, with geographical and ethnic differences in the frequency of specific chromosomal aberrations. This article compared the cytogenetic data of 36 adult Omani patients with MDS to previously reported data from other populations. Differences were noted between the percentages of clonal aberrations and the median age of Omani subjects at presentation in comparison to individuals of different ethnicities and from various geographical locations. To the best of the authors’ knowledge, this is the first report to describe the cytogenetic data of patients with MDS from Oman.

  10. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ayed A. Algarni

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature.

  11. Prognostic factors in lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Starklint, Henrik; Halberg, Poul

    2006-01-01

    To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis.......To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis....

  12. Requirements Specifications for Prognostics: An Overview

    Data.gov (United States)

    National Aeronautics and Space Administration — With recent advancements in prognostics methodologies there has been a significant interest in maturing Prognostics and Health Management (PHM) to increase its...

  13. Metrics for Offline Evaluation of Prognostic Performance

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostic performance evaluation has gained significant attention in the past few years.*Currently, prognostics concepts lack standard definitions and suffer from...

  14. On Applying the Prognostic Performance Metrics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics performance evaluation has gained significant attention in the past few years. *As prognostics technology matures and more sophisticated methods for...

  15. Impaired Expression of Focal Adhesion Kinase in Mesenchymal Stromal Cells from Low-Risk Myelodysplastic Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Yuenv Wu

    2017-08-01

    Full Text Available The pathogenic role of mesenchymal stromal cells (MSCs in myelodysplastic syndromes (MDS development and progression has been investigated by numerous studies, yet, it remains controversial in some aspects (1, 2. In the present study, we found distinct features of MSCs from low-risk (LR-MDS stromal microenvironment as compared to those from healthy subjects. At the molecular level, focal adhesion kinase, a key tyrosine kinase in control of cell proliferation, survival, and adhesion process, was found profoundly suppressed in expression and activation in LR-MDS MSC. At a functional level, LR-MDS MSCs showed impaired growth and clonogenic capacity, which were independent of cellular senescence and apoptosis. The pro-adipogenic differentiation and attenuated osteogenic capacity along with reduced SDF-1 expression could be involved in creating an unfavorable microenvironment for hematopoiesis. In conclusion, our experiments support the theory that the stromal microenvironment is fundamentally altered in LR-MDS, and these preliminary data offer a new perspective on LR-MDS pathophysiology.

  16. Integrated genomic analysis implicates haploinsufficiency of multiple chromosome 5q31.2 genes in de novo myelodysplastic syndromes pathogenesis.

    Directory of Open Access Journals (Sweden)

    Timothy A Graubert

    Full Text Available Deletions spanning chromosome 5q31.2 are among the most common recurring cytogenetic abnormalities detectable in myelodysplastic syndromes (MDS. Prior genomic studies have suggested that haploinsufficiency of multiple 5q31.2 genes may contribute to MDS pathogenesis. However, this hypothesis has never been formally tested. Therefore, we designed this study to systematically and comprehensively evaluate all 28 chromosome 5q31.2 genes and directly test whether haploinsufficiency of a single 5q31.2 gene may result from a heterozygous nucleotide mutation or microdeletion. We selected paired tumor (bone marrow and germline (skin DNA samples from 46 de novo MDS patients (37 without a cytogenetic 5q31.2 deletion and performed total exonic gene resequencing (479 amplicons and array comparative genomic hybridization (CGH. We found no somatic nucleotide changes in the 46 MDS samples, and no cytogenetically silent 5q31.2 deletions in 20/20 samples analyzed by array CGH. Twelve novel single nucleotide polymorphisms were discovered. The mRNA levels of 7 genes in the commonly deleted interval were reduced by 50% in CD34+ cells from del(5q MDS samples, and no gene showed complete loss of expression. Taken together, these data show that small deletions and/or point mutations in individual 5q31.2 genes are not common events in MDS, and implicate haploinsufficiency of multiple genes as the relevant genetic consequence of this common deletion.

  17. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

    Science.gov (United States)

    Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

    2018-01-01

    The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

  18. Colorectal Cancer: Prognostic Values

    Directory of Open Access Journals (Sweden)

    Suzana Manxhuka-Kerliu

    2009-02-01

    Full Text Available After lung cancer colorectal cancer (Cc is ranked the second, as a cause of cancer-related death. The purpose of this study was to analyze the Cc cases in our material with respect to all prognostic values including histological type and grade, vascular invasion, perineural invasion, and tumor border features. There were investigated 149 cases of resection specimen with colorectal cancer, which were fixed in buffered neutral formalin and embedded in paraffin. Tissue sections (4(µm thick were cut and stained with H&E. Adenocarcinoma was the most frequent histological type found in 85,90% of cases, in 60,94% of males and 39,06% of females; squamous cell carcinoma in 7,38%, in 63,63% of males and 36,36% of females; mucinous carcinoma in 4,68%, in 57,15% of males and 42,85% of females; while adenosquamous carcinoma, undifferentiated carcinoma and carcinoma in situ in 0,71% of cases each. Dukes' classification was used in order to define the depth of invasion. Dukes B was found in 68,45% of cases, whereas in 31,54% of cases Dukes C was found. As far as histological grading is concerned, Cc was mostly with moderate differentiation (75,16% with neither vascular nor perineural invasion. Resection margins were in all cases free of tumor. Our data indicate that the pathologic features of the resection specimen constitute the most powerful predictors of postoperative outcome in Cc. Dukes' stage and degree of differentiation provide independent prognostic information in Cc. However, differentiation should be assessed by the worst pattern.

  19. Application of Multidimensional Scaling (MDS) to the analysis of media discourse. The case of the media coverage of ‘escraches’

    OpenAIRE

    Albizu Landa, Xabier

    2014-01-01

    En el presente artículo se discuten las posibilidades que ofrece la técnica de análisis multivariante conocida como Escalamiento Multidimensional (MDS) para el análisis del discurso periodístico y la determinación de los frames presentes en este. En una primera parte se repasan las tradiciones de los análisis de framing y de la aplicación del MDS. En una segunda parte se presenta un caso práctico en el que el MDS es utilizado para la determinación de los frames presentes en la cobertura perio...

  20. Speech-activated Myoclonus Mimicking Stuttering in a Patient with Myoclonus–Dystonia Syndrome

    Directory of Open Access Journals (Sweden)

    Peter Hedera

    2016-07-01

    Full Text Available Background: Acquired neurogenic stuttering has been considered a fairly uncommon clinical occurrence; speech-activated myoclonus is a rare entity that can mimic stuttering and is caused by a wide array of etiologies.Case Report: Here we report a patient with myoclonus–dystonia syndrome (MDS, due to an identified disease-causing mutation, who displayed speech-activated myoclonus mimicking stuttering.Discussion: In MDS, myoclonus has only infrequently been reported to affect speech. This case further expands the spectrum of conditions causing the rare clinical phenomenon of speech-activated myoclonus. 

  1. Molecular analysis of myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5 reveals a specific spectrum of molecular mutations with prognostic impact: a study on 123 patients and 27 genes

    Science.gov (United States)

    Meggendorfer, Manja; Haferlach, Claudia; Kern, Wolfgang; Haferlach, Torsten

    2017-01-01

    The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, which, along with morphological features, leads to the diagnosis of myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5. These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia; however, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated deletion of the long arm of chromosome 5, diagnosed following the World Health Organization classifications 2008 and 2016, by sequencing 27 genes. A great proportion of patients showed no or only one mutation. Only seven genes showed mutation frequencies >5% (SF3B1, DNMT3A, TP53, TET2, CSNK1A1, ASXL1, JAK2). However, the pattern of recurrently mutated genes was comparable to other myelodysplastic syndrome subtypes by comparison to a reference cohort, except that of TP53 which was significantly more often mutated in myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5. As expected, SF3B1 was frequently mutated and correlated with ring sider-oblasts, while JAK2 mutations correlated with elevated platelet counts. Surprisingly, SF3B1 mutations led to significantly worse prognosis within cases with isolated deletion of the long arm of chromosome 5, but showed a comparable outcome to other myelodysplastic syndrome subtypes with SF3B1 mutation. However, addressing genetic stability in follow-up cases might suggest different genetic mechanisms for progression to secondary acute myeloid leukemia compared to overall myelodysplastic syndrome patients. PMID:28642303

  2. Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications

    Directory of Open Access Journals (Sweden)

    Lisa Pleyer

    2016-04-01

    .9 vs 24.4 months; p < 0.001. Conclusions Our data demonstrate the validity of the WHO classification of MDS and AML, and its superiority over the former FAB classification, for patients treated with azacitidine front-line. Neither bone marrow blast count nor presence of MDS-related features had an adverse prognostic impact on survival. Patients with AML20–30 should therefore be regarded as having ‘true AML’ and in our opinion treatment should be initiated without delay.

  3. Occupational, dietary, and other risk factors for myelodysplastic syndromes in Western Greece.

    Science.gov (United States)

    Avgerinou, Christina; Giannezi, Ioanna; Theodoropoulou, Stela; Lazaris, Vasileios; Kolliopoulou, Georgia; Zikos, Panagiotis; Alamanos, Yannis; Leotsinidis, Michalis; Symeonidis, Argiris

    2017-08-01

    We have observed an increasing incidence of myelodysplastic syndromes (MDS) in the geographic area of Western Greece during the past two decades. The objective of this study was to investigate potential risk factors for the manifestation of MDS in this area of Greece. A hospital-based case-control study was conducted in the public hospitals of the region. Participants were interviewed based on a questionnaire regarding demographics, occupational exposures, smoking, alcohol consumption, dietary, and domestic factors. A total of 228 individuals (126 cases, 102 controls) were recruited in this study. Univariate analysis showed that risk of MDS was associated with a family history of hematologic malignancy or solid tumor, exposure to pesticides, insecticides, herbicides, increased weekly intake of meat and eggs, and increased alcohol intake, whereas fruit intake had a protective effect. Analysis by pesticide ingredient showed a weak association of exposure to paraquat and glyphosate with the occurrence of MDS. Multivariate analysis showed that independent risk factors for the manifestation of MDS were family history of solid tumor (OR 2.47, 95% CI 1.32-4.65), meat intake for ≥5 days/week (OR 2.67, 95% CI 1.05-6.80) and exposure to pesticides (OR 3.25, 95% CI 1.73-6.11). Exposure to pesticides is a major risk factor of MDS in Western Greece. Family history of solid tumor and increased meat intake also appear to play a role in the pathogenesis of MDS. Public health authorities should implement policies to advise and protect farmers from the harmful effects of agrochemicals. Emphasis should also be given to health promotion advice including healthy eating.

  4. Myelodysplastic syndrome

    Science.gov (United States)

    ... your provider plan your treatment. Your provider may define your MDS as high-risk, intermediate-risk, or ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  5. Towards Prognostics for Electronics Components

    Data.gov (United States)

    National Aeronautics and Space Administration — Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is...

  6. Standardizing Research Methods for Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics and health management (PHM) is a maturing system engineering discipline. As with most maturing disciplines, PHM does not yet have a universally accepted...

  7. Modeling for Battery Prognostics

    Science.gov (United States)

    Kulkarni, Chetan S.; Goebel, Kai; Khasin, Michael; Hogge, Edward; Quach, Patrick

    2017-01-01

    For any battery-powered vehicles (be it unmanned aerial vehicles, small passenger aircraft, or assets in exoplanetary operations) to operate at maximum efficiency and reliability, it is critical to monitor battery health as well performance and to predict end of discharge (EOD) and end of useful life (EOL). To fulfil these needs, it is important to capture the battery's inherent characteristics as well as operational knowledge in the form of models that can be used by monitoring, diagnostic, and prognostic algorithms. Several battery modeling methodologies have been developed in last few years as the understanding of underlying electrochemical mechanics has been advancing. The models can generally be classified as empirical models, electrochemical engineering models, multi-physics models, and molecular/atomist. Empirical models are based on fitting certain functions to past experimental data, without making use of any physicochemical principles. Electrical circuit equivalent models are an example of such empirical models. Electrochemical engineering models are typically continuum models that include electrochemical kinetics and transport phenomena. Each model has its advantages and disadvantages. The former type of model has the advantage of being computationally efficient, but has limited accuracy and robustness, due to the approximations used in developed model, and as a result of such approximations, cannot represent aging well. The latter type of model has the advantage of being very accurate, but is often computationally inefficient, having to solve complex sets of partial differential equations, and thus not suited well for online prognostic applications. In addition both multi-physics and atomist models are computationally expensive hence are even less suited to online application An electrochemistry-based model of Li-ion batteries has been developed, that captures crucial electrochemical processes, captures effects of aging, is computationally efficient

  8. Effects of rasagiline on the progression of nonmotor scores of the MDS-UPDRS.

    Science.gov (United States)

    Poewe, Werner; Hauser, Robert A; Lang, Anthony

    2015-04-01

    A draft version of part 1 (Non-Motor Aspects of Experiences of Daily Living; nM-EDL) of the MDS-UPDRS scale was employed as a secondary outcome in the ADAGIO study, which assessed the effect of rasagiline in early Parkinson's disease (PD) patients. This analysis includes 1,150 untreated PD patients randomized to placebo or rasagiline 1 or 2 mg/day for 36 weeks in the placebo-controlled phase of ADAGIO who had draft-nM-EDL assessments at baseline and week 36. Over the 9-month placebo-controlled phase of the study, nM-EDL scores significantly deteriorated from baseline in the placebo group only (0.34 ± 0.10 units; P rasagiline group (n = 280; treatment effect: -0.33 units; P rasagiline group (n = 287) was not statistically significant (-0.25 ± 0.17 units; P = 0.131). The nM-EDL subscale appears sensitive to change in very early PD, and treatment with rasagiline 1 mg/day was associated with significantly less decline in nonmotor experiences of daily living versus placebo. Given that score changes were numerically small, the clinical implications of this effect remain unclear. © 2014 International Parkinson and Movement Disorder Society.

  9. Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

    Science.gov (United States)

    Zeidan, Amer M; Hendrick, Franklin; Friedmann, Erika; Baer, Maria R; Gore, Steven D; Sasane, Medha; Paley, Carole; Davidoff, Amy J

    2015-01-01

    Aims: Iron overload adversely affects patients with myelodysplastic syndromes (MDS), but benefits of iron chelation therapy have not been clearly demonstrated. We examined the association between deferasirox (DFX) therapy and mortality in transfusion-receiving Medicare patients. Patients & methods: MDS patients from 2005 to 2008 were identified using ICD-9 codes from 100% Medicare claims. Patients receiving ≥20 blood units were observed until death or end of study. Marginal structural models were used for estimation. Results: 3926 patients (10.1% used DFX) were observed for a mean of 48.8 weeks. Each incremental week of DFX was associated with a significant reduction in mortality risk (hazard ratio [HR]: 0.989; 95% CI: 0.983–0.996; p = 0.001). Conclusion: DFX therapy is associated with a reduced mortality risk among older MDS patients who received a minimum transfusion threshold. PMID:26274794

  10. Bone marrow dendritic cells are reduced in patients with high-risk myelodysplastic syndromes.

    Science.gov (United States)

    Saft, Leonie; Björklund, Elisabet; Berg, Elisabeth; Hellström-Lindberg, Eva; Porwit, Anna

    2013-03-01

    Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in coordinating functions of the immune system. Previous studies suggest that bone marrow (BM) failure in myelodysplastic syndromes (MDS) may be in part immune-mediated, and that the high propensity for relapse may reflect decreased immune surveillance. This study aimed to assess the frequency of DC in BM samples from well-annotated untreated MDS patients by using 4-colour flow cytometry. DC levels were markedly reduced in all subtypes of MDS. The clinical impact of this finding on therapy response and relapse after, e.g. allogeneic stem cell transplantation warrants further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. [Cold autoimmune hemolytic anemia complicated with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation].

    Science.gov (United States)

    Okamura, Hiroshi; Nakane, Takahiko; Fujino, Keizo; Koh, Shiro; Yoshimura, Takuro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Koh, Hideo; Nakao, Yoshitaka; Nakamae, Hirohisa; Hino, Masayuki

    2015-04-01

    Myelodysplastic syndrome (MDS) is known to often be complicated by a range of autoimmune diseases. We herein present a case with MDS complicated by cold autoimmune hemolytic anemia (cold AIHA). The patient was a 51-year-old woman. She was diagnosed with MDS (refractory cytopenia with multilineage dysplasia) in May 2009. In January 2010, she underwent unrelated allogeneic bone marrow transplantation but was re-admitted in October 2010 for treatment of relapsed MDS. Despite daily transfusions of red blood cells, her anemia failed to improve. Her laboratory examinations showed a low haptoglobin level and elevation of indirect bilirubin and LDH. The direct Coombs test was positive at a low and at room temperature and cold agglutinin was negative. After confirming the diagnosis of cold AIHA, all transfusion fluids were warmed but her anemia still failed to improve. In addition to the warmed transfusion fluids, we administered corticosteroids, immunosuppressive agents and high-dose intravenous immunoglobulin infusions. This management strategy ameliorated the patient's hemolytic anemia. To our knowledge, MDS cases complicated by cold AIHA are rare. Our patient thus provides a valuable contribution to medical knowledge.

  12. Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research.

    Science.gov (United States)

    Zhou, Ting; Kinney, Marsha C; Scott, Linda M; Zinkel, Sandra S; Rebel, Vivienne I

    2015-08-27

    Much-needed attention has been given of late to diseases specifically associated with an expanding elderly population. Myelodysplastic syndrome (MDS), a hematopoietic stem cell-based blood disease, is one of these. The lack of clear understanding of the molecular mechanisms underlying the pathogenesis of this disease has hampered the development of efficacious therapies, especially in the presence of comorbidities. Mouse models could potentially provide new insights into this disease, although primary human MDS cells grow poorly in xenografted mice. This makes genetically engineered murine models a more attractive proposition, although this approach is not without complications. In particular, it is unclear if or how myelodysplasia (abnormal blood cell morphology), a key MDS feature in humans, presents in murine cells. Here, we evaluate the histopathologic features of wild-type mice and 23 mouse models with verified myelodysplasia. We find that certain features indicative of myelodysplasia in humans, such as Howell-Jolly bodies and low neutrophilic granularity, are commonplace in healthy mice, whereas other features are similarly abnormal in humans and mice. Quantitative hematopoietic parameters, such as blood cell counts, are required to distinguish between MDS and related diseases. We provide data that mouse models of MDS can be genetically engineered and faithfully recapitulate human disease. © 2015 by The American Society of Hematology.

  13. Dysregulated microRNA Activity in Shwachman-Diamond Syndrome

    Science.gov (United States)

    2016-09-01

    thrombocytopenia, pan-anemia and myelodysplasia (MDS) with progression to acute myeloid leukemia (AML). The affected cell types and altered genetic...13. SUPPLEMENTARY NOTES 14. ABSTRACT Shwachman-Diamond Syndrome (SDS) is an inherited bone marrow failure primarily affecting myeloid development...myelopoiesis; targeted RNA-seq 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON

  14. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

    DEFF Research Database (Denmark)

    Gattermann, Norbert; Finelli, Carlo; Porta, Matteo Della

    2010-01-01

    The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500ng/mL, approximately 50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether...

  15. Adult mitochondrial DNA depletion syndrome with mild manifestations

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2013-06-01

    Full Text Available Mitochondrial DNA depletion syndrome (MDS is usually a severe disorder of infancy or childhood, due to a reduced copy number of mtDNA molecules. MDS with only mild, non-specific clinical manifestations and onset in adulthood has not been reported. A 47-year-old Caucasian female with short stature and a history of migraine, endometriosis, Crohn’s disease, C-cell carcinoma of the thyroid gland, and a family history positive for mitochondrial disorder (2 sisters, aunt, niece, developed day-time sleepiness, exercise intolerance, and myalgias in the lower-limb muscles since age 46y. She slept 9-10 hours during the night and 2 hours after lunch daily. Clinical exam revealed sore neck muscles, bilateral ptosis, and reduced Achilles tendon reflexes exclusively. Blood tests revealed hyperlipidemia exclusively. Nerve conduction studies, needle electromyography, and cerebral and spinal magnetic resonance imaging were non-informative. Muscle biopsy revealed detached lobulated fibers with subsarcolemmal accentuation of the NADH and SDH staining. Real-time polymerase chain reaction revealed depletion of the mtDNA down to 9% of normal. MDS may be associated with a mild phenotype in adults and may not significantly progress during the first year after onset. In an adult with hypersomnia, severe tiredness, exercise intolerance, and a family history positive for mitochondrial disorder, a MDS should be considered.

  16. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Mariane de Montalembert

    Full Text Available The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS. In patients with sickle cell anemia (SCA, iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15% patients with thalassemia, none with SCA, and 4 (16% with MDS. The liver iron content (LIC ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29. Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001. Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001. Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

  17. Evaluation of comorbidities at diagnosis predicts outcome in myelodysplastic syndrome patients.

    Science.gov (United States)

    Breccia, Massimo; Federico, Vincenzo; Latagliata, Roberto; Mercanti, Caterina; D'Elia, Gianna Maria; Cannella, Laura; Loglisci, Giuseppina; Salaroli, Adriano; Santopietro, Michelina; Alimena, Giuliana

    2011-02-01

    Recent data suggest that proper assessment of comorbidities is useful to predict the outcome of MDS patients receiving allogeneic stem cell transplantation. However, the results obtained in this highly selected subset of patients cannot be applied to the whole MDS population. We evaluated the impact of comorbidities in 418 consecutive MDS patients diagnosed at our institute from 1992 to 2005. All patients were classified according to WHO criteria and all received only conservative and supportive treatment. One or more comorbidities were detected in 390 patients (93%) at the time of diagnosis, with a higher incidence in older patients. Cardiac diseases were the most frequent comorbidities (30%) while diabetes and correlated adverse events were the second cause of comorbidity (20%). We applied 3 comorbidity prognostic scores (CCI, HCT-CI and a MDS-CI score proposed by Della Porta et al.). According to CCI score, 253 patients had a score 0, 111 patients had a score 1 and 54 patients had a score >2. According to HCT-CI, 209 patients had a score 0, 105 patients had a score 1 and 106 patients had a score >2. With MDS-CI score, 288 patients had a score 0 and 129 patients had a score >1. We found a significant correlation between survival and stratification according to CCI and MDS-CI scores (p=0.01 and 0.02, respectively), but not according to HCT-CI score. The number of comorbidities as evaluated according to CCI was directly correlated to the development of RBC transfusion-dependency and was associated to a significantly higher risk of death not related to leukemic evolution (HR = 2.12, p ≤ 0.001). Conversely, higher risk of non-leukemic death did not correlate with higher transfusional requirement according to HCT-CI and MDS-CI scores (p = 0.3 and 0.43, respectively). As suggested by Della Porta et al., also in our experience the presence of cardiac, liver, renal, pulmonary diseases and solid tumours was found to independently affect the risk of death in a

  18. The Mice Drawer System Tissue Sharing Program (MDS-TSP): osteobiology in microgravity

    Science.gov (United States)

    Ruggiu, Alessandra; Cancedda, Ranieri; Biticchi, Roberta; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Tasso, Roberta; Tavella, Sara

    The capacity of bone tissue to alter its mass and architecture in response to mechanical request has long been known. Bone not only develops as a structure designed specifically for mechanical demands, but it can adapt during life toward more efficient mechanical performance. In partic-ular, the skeletal effects of microgravity result in the development of an osteoporotic phenotype with several bone defects including a bone mass decrease resembling the bone modifications occurring in elder people and in bed rest conditions. This is particularly true for weight bearing bones such as spine, femur and tibiae. In contrast non-weight bearing bones like calvaria etc didn't show bone mineral density decrease in weightlessness. Given the interest of our labora-tory in the microgravity induced skeleton alterations, we focused our attention on a transgenic mouse overexpressing pleiotrophin (PTN) under the control of the bone specific human os-teocalcin promoter. This protein is a heparin-binding cytokine with different functions. In particular PTN-transgenic mice (PTN-Tg) show an increase in the bone mass and mineral-ization, with a calcium content/mg bone of 10We used this mouse model in the MDS flight experiment to study the PTN potential role in counteracting bone loss in microgravity. Three PTN-transgenic mice (Tg) and three wild type (Wt) mice were housed in the MDS (Mouse Drawer System) at the ISS for three months. During these three months two wt and one tg mice died and therefore could be only frozen for subsequent skeletal analysis. The other three mice, daily checked for their health status, were viable and in good condition throughout the all three months at the ISS. At the end of November 2009 the three mice came back to Earth and after blood collection were immediately sacrificed and the different bones isolated. From blood cell analysis no major hematological alterations were noticed in the blood cell count except a slight increase in the number of erythrocytes

  19. A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor.

    Science.gov (United States)

    Rogers, Kerry A; Huang, Ying; Ruppert, Amy S; Salem, Galena; Stephens, Deborah M; Heerema, Nyla A; Andritsos, Leslie A; Awan, Farrukh T; Byrd, John C; Flynn, Joseph M; Maddocks, Kami J; Jones, Jeffrey A

    2018-01-01

    Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline-based chemoimmunotherapy regimens designed to treat de novo diffuse large B-cell lymphoma achieve modest clinical benefit. R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B-cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first-line R-EPOCH at our institution between 1 January 2006 and 31 May 2014. The median progression-free survival (PFS) was 3·5 months [95% confidence interval (CI): 2·0-7·6] and median overall survival (OS) was 5·9 months (95% CI: 3·2-10·3). Toxicity was high and 30% of patients died without progression or response. Patients with a complex CLL karyotype had significantly shorter PFS and OS (P = 0·005 and P = 0·002, respectively). Multivariable analysis identified complex CLL karyotype as the most significant predictor of decreased survival [Hazard ratio (HR) 2·72, 95% CI: 1·14-6·52, P = 0·025], adjusting for number of prior CLL treatments (P = 0·036). Richter Syndrome patients with complex CLL karyotype experience poor survival with R-EPOCH treatment and novel approaches are needed for these patients. In contrast, survival of patients without a complex CLL karyotype was similar to patients with de novo diffuse large B-cell lymphoma. © 2017 John Wiley & Sons Ltd.

  20. Clinical significance of previously cryptic copy number alterations and loss of heterozygosity in pediatric acute myeloid leukemia and myelodysplastic syndrome determined using combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray analyses.

    Science.gov (United States)

    Koh, Kyung-Nam; Lee, Jin Ok; Seo, Eul Ju; Lee, Seong Wook; Suh, Jin Kyung; Im, Ho Joon; Seo, Jong Jin

    2014-07-01

    The combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH+SNP microarray) platform can simultaneously detect copy number alterations (CNA) and copy-neutral loss of heterozygosity (LOH). Eighteen children with acute myeloid leukemia (AML) (n=15) or myelodysplastic syndrome (MDS) (n=3) were studied using CGH+SNP microarray to evaluate the clinical significance of submicroscopic chromosomal aberrations. CGH+SNP microarray revealed CNAs at 14 regions in 9 patients, while metaphase cytogenetic (MC) analysis detected CNAs in 11 regions in 8 patients. Using CGH+SNP microarray, LOHs>10 Mb involving terminal regions or the whole chromosome were detected in 3 of 18 patients (17%). CGH+SNP microarray revealed cryptic LOHs with or without CNAs in 3 of 5 patients with normal karyotypes. CGH+SNP microarray detected additional cryptic CNAs (n=2) and LOHs (n=5) in 6 of 13 patients with abnormal MC. In total, 9 patients demonstrated additional aberrations, including CNAs (n=3) and/or LOHs (n=8). Three of 15 patients with AML and terminal LOH>10 Mb demonstrated a significantly inferior relapse-free survival rate (P=0.041). This study demonstrates that CGH+SNP microarray can simultaneously detect previously cryptic CNAs and LOH, which may demonstrate prognostic implications.

  1. Acute Myeloid Leukemia and Myelodysplastic Syndromes After Radiation Therapy Are Similar to De Novo Disease and Differ From Other Therapy-Related Myeloid Neoplasms

    Science.gov (United States)

    Nardi, Valentina; Winkfield, Karen M.; Ok, Chi Young; Niemierko, Andrzej; Kluk, Michael J.; Attar, Eyal C.; Garcia-Manero, Guillermo; Wang, Sa A.; Hasserjian, Robert P.

    2012-01-01

    Purpose Therapy-related myeloid neoplasms (t-MN) represent a unique clinical syndrome occurring in patients treated with chemotherapy and/or external-beam radiation (XRT) and are characterized by poorer prognosis compared with de novo disease. XRT techniques have evolved in recent years and are associated with significantly reduced bone marrow exposure. The characteristics of post-XRT t-MN in the current era have not been studied. Patients and Methods We analyzed patients who developed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) after XRT alone (47 patients) or cytotoxic chemotherapy/combined-modality therapy (C/CMT, 181 patients) and compared them with patients with de novo MDS or AML (222 patients). We estimated bone marrow exposure to radiation and compared the clinical, pathologic, and cytogenetic features and outcome of the XRT patients with the C/CMT patients and with patients with de novo MDS and AML. Results Patients with t-MN after XRT alone had superior overall survival (P = .006) and lower incidence of high-risk karyotypes (P = .01 for AML and < .001 for MDS) compared with patients in the C/CMT group. In contrast, there were no significant differences in survival or frequency of high-risk karyotypes between the XRT and de novo groups. Conclusion AML and MDS diagnosed in the past decade in patients after receiving XRT alone differ from t-MN occurring after C/CMT and share genetic features and clinical behavior with de novo AML/MDS. Our results suggest that post-XRT MDS/AML may not represent a direct consequence of radiation toxicity and warrant a therapeutic approach similar to de novo disease. PMID:22585703

  2. The development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): a large-scale data sharing initiative.

    Science.gov (United States)

    Lutomski, Jennifer E; Baars, Maria A E; Schalk, Bianca W M; Boter, Han; Buurman, Bianca M; den Elzen, Wendy P J; Jansen, Aaltje P D; Kempen, Gertrudis I J M; Steunenberg, Bas; Steyerberg, Ewout W; Olde Rikkert, Marcel G M; Melis, René J F

    2013-01-01

    In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons' health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu). A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden). Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies. TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations

  3. The MDS-UPDRS tracks motor and non-motor improvement due to subthalamic nucleus deep brain stimulation in Parkinson disease.

    Science.gov (United States)

    Chou, Kelvin L; Taylor, Jennifer L; Patil, Parag G

    2013-11-01

    The Movement Disorders Society revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) improves upon the original UPDRS by adding more non-motor items, making it a more robust tool to evaluate the severity of motor and non-motor symptoms of Parkinson disease. Previous studies on deep brain stimulation have not used the MDS-UPDRS. To determine if the MDS-UPDRS could detect improvement in both motor and non-motor symptoms after bilateral subthalamic nucleus deep brain stimulation for Parkinson disease. We compared scores on the entire MDS-UPDRS prior to surgery (baseline) and approximately six months following the initial programming visit in twenty subjects (12M/8F) with Parkinson disease undergoing bilateral subthalamic nucleus deep brain stimulation. STN DBS significantly improved the scores for every section of the MDS-UPDRS at the 6 month follow-up. Part I improved by 3.1 points (22%), Part II by 5.3 points (29%), Part III by 13.1 points (29%) with stimulation alone, and Part IV by 7.1 points (74%). Individual non-motor items in Part I that improved significantly were constipation, light-headedness, and fatigue. Both motor and non-motor symptoms, as assessed by the MDS-UPDRS, improve with bilateral subthalamic nucleus stimulation six months after the stimulator is turned on. We recommend that the MDS-UPDRS be utilized in future deep brain stimulation studies because of the advantage of detecting change in non-motor symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. [Myelodysplastic syndrome classification].

    Science.gov (United States)

    Ghariani, Ines; Braham, Najia; Hassine, Mohsen; Kortas, Mondher

    2013-01-01

    Myelodysplastic syndromes (MDS) are myeloid disorders with various clinical and biological presentations. The French-American-British (FAB-1982) classification included five categories basing on morphology and bone marrow blast count. Three criteria are taken into account: 1) the percentage of blasts in peripheral blood and bone marrow, 2) the percentage of ringed sideroblasts, and 3) the number of monocytes in peripheral blood. The World Health Organization classification (WHO 2001, 2008) modifies the FAB system by also taking cytogenetic characteristics and molecular biology into consideration. The last classification (WHO-2008) takes into account: 1) the number of peripheral cytopenia, 2) the percentage of blasts in peripheral blood and bone marrow, 3) the percentage of ringed sideroblasts, 4) the possible presence of Auer Rods, and 5) the detection of a cytogenetic abnormality (the isolated 5q deletion). The following subgroups are defined: refractory cytopenia with unilineage dysplasia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts, myelodysplastic syndrome unclassifiable and myelodysplastic syndrome with isolated del(5q).

  5. Diabetes Insipidus as an Initial Presentation of Myelodysplastic Syndrome: Diagnosis with Single-Nucleotide Polymorphism Array-Based Karyotyping.

    Science.gov (United States)

    Sun, Ruixue; Wang, Chun; Zhong, Xushu; Wu, Yu

    2016-04-01

    Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic diseases characterized by cytopenia, dysplasia and increased risk of development to acute myeloid leukemia (AML). Unfavorable cytogenetic changes such as complex karyotypes or chromosome 7 anomalies are predictive of the progression to AML and poor prognosis. Central diabetes insipidus (CDI) is the result of a deficiency of arginine vasopressin, and its major causes are idiopathic, primary or secondary tumors, neurosurgery and trauma. Importantly, CDI is a rare complication of MDS. To date, only 5 cases of MDS co-occurring with CDI have been reported; 3 of 5 had cytogenetic abnormalities uncovered by metaphase cytogenetics and 3 of 5 evolved to AML. Here, we describe a 74-year-old woman who presented with CDI as her initial symptom of MDS and eventually progressed to AML. The metaphase cytogenetics, combined with the single-nucleotide polymorphism array (SNP-A)-based karyotyping, with superiority in resolution and detecting copy number variation, revealed a complex karyotype that included monosomy of chromosome 7, deletion of 20q, and absence of heterogeneity (AOH) in more than one chromosome. To the best of our knowledge, this is the first case report of MDS co-occurring with CDI with numerous cytogenetic abnormalities revealed by the SNP-A-based karyotyping. Our case supports that the cytogenetic abnormalities may be associated with the clinical features and the prognosis of MDS co-occurring with CDI. The SNP-A-based karyotyping is helpful in revealing more subtle cytogenetic abnormalities and unveiling their roles in the pathogenesis of MDS.

  6. Coffee and green tea consumption and subsequent risk of acute myeloid leukemia and myelodysplastic syndromes in Japan.

    Science.gov (United States)

    Ugai, Tomotaka; Matsuo, Keitaro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Goto, Atsushi; Inoue, Manami; Kanda, Yoshinobu; Tsugane, Shoichiro

    2018-03-15

    Although coffee and green tea are suggested to reduce the risk of some types of cancers, only a few epidemiological studies have investigated their effect on the risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here, we investigated the association of coffee and green tea consumption and the risk of AML and MDS in a large-scale population-based cohort study in Japan. A total of 95,807 Japanese subjects (45,937 men and 49,870 women; age 40-69 years at baseline) were followed to the end of 2012, for an average of 18 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between coffee and green tea consumption at baseline and the risk of AML and MDS were assessed using a Cox proportional hazards model with adjustment for potential confounders. During 1,751.956 person-years, we identified 85 AML cases and 70 MDS cases. Our findings showed no significant association between coffee consumption and the risk of AML, or between green tea consumption and the risk of AML or MDS. In contrast, we observed a decreasing dose-response relationship between coffee consumption and the risk of MDS among men (almost none: reference, 1-4 times/week: HR = 0.83, 95% CI: 0.43-1.62; ≥1cups/day: HR = 0.47, 0.22-0.99, p for trend = 0.049). Stratified analysis by smoking status suggested that the observed relative risk for AML and MDS of coffee drinkers relative to non-coffee drinkers might be due to residual confounding by smoking. These findings deserve further investigation in future studies. © 2017 UICC.

  7. The Clinical Importance of Moderate/Severe Bone Marrow Fibrosis in Patients with Therapy-related Myelodysplastic Syndromes

    Science.gov (United States)

    Fu, Bin; OK, Chi Young; Goswami, Maitrayee; Xei, Wei; Jaso, Jesse M; Muzzafar, Tariq; Bueso-Ramos, Carlos; Verstovsek, Srdan; Garcia-Manero, Guillermo; Medeiros, L. Jeffrey; Wang, Sa A.

    2014-01-01

    Background The presence of moderate to severe bone marrow (BM) fibrosis has been shown to be an adverse feature in patients with primary myelodysplastic syndromes (MDS). However, the clinical importance of BM fibrosis is not clear in therapy-related MDS. Methods We retrieved all t-MDS cases (n=266) diagnosed at our hospital over a 10-year period (2003–2012). Reticulin and trichromestains were performed in cases in which BM fibrosis was suspected on initial evaluation of hematoxylin & eosin stained slide. BM fibrosis was graded according to European consensus guidelines, and a score of MF2/MF3 was defined as moderate/severe fibrosis. Result Moderate/severe BM fibrosis was found in 47 (17%) patients. Compared to 219 patients with no/mild BM fibrosis, the patients with moderate/severe fibrosis presented with severer thrombocytopenia (p=0.039), higher numbers of circulating blasts (p=0.051) but similar degrees of anemia and neutropenia, transfusion requirements, and similar incidences of hepatosplenomegaly and constitutional symptoms. Histological examination revealed a comparable BM cellularity and BM blast percentage, but markedly increased megakaryocytes (p<0.001) in the fibrotic group. Although the risk distribution of cytogenetic data was similar according to the New Comprehensive Cytogenetic Scoring criteria, −5 and −17 were more frequently observed in t-MDS with moderate/severe BM fibrosis (p=0.031 and p=0.043 respectively). With a median follow-up of 11.5 months, patients with moderate/severe BM fibrosis showed a similar risk of acute myeloid leukemia transformation, and a comparable overall survival in univariate and multivariate analyses. Conclusions Moderate/severe BM fibrosis in patients with t-MDS is associated with certain clinicopathological and genetic features. However, unlike the situation in patients with primary MDS, moderate/severe BM fibrosis does not add additional risk to patients with therapy-related MDS. PMID:23660629

  8. Prognostic Factors in Hodgkin's Disease

    DEFF Research Database (Denmark)

    Specht

    1996-01-01

    regions and the tumor mass in each region are important, and an estimate of the total tumor burden has proved significant. B symptoms, histological subtype, age, and gender are also generally significant but less important. Prognostic factors for laparotomy findings in clinical stages I and II are: number...... of involved regions, disease confined to upper cervical nodes, B symptoms, gender, histology, age, and mediastinal disease (variable influence). In clinical stages I and II, the same prognostic factors apply as for pathological stages I and II and for laparotomy findings, and also some indirect indicators...

  9. Distributed Prognostics Based on Structural Model Decomposition

    Data.gov (United States)

    National Aeronautics and Space Administration — Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based...

  10. A Generic Software Architecture For Prognostics

    Science.gov (United States)

    Teubert, Christopher; Daigle, Matthew J.; Sankararaman, Shankar; Goebel, Kai; Watkins, Jason

    2017-01-01

    Prognostics is a systems engineering discipline focused on predicting end-of-life of components and systems. As a relatively new and emerging technology, there are few fielded implementations of prognostics, due in part to practitioners perceiving a large hurdle in developing the models, algorithms, architecture, and integration pieces. As a result, no open software frameworks for applying prognostics currently exist. This paper introduces the Generic Software Architecture for Prognostics (GSAP), an open-source, cross-platform, object-oriented software framework and support library for creating prognostics applications. GSAP was designed to make prognostics more accessible and enable faster adoption and implementation by industry, by reducing the effort and investment required to develop, test, and deploy prognostics. This paper describes the requirements, design, and testing of GSAP. Additionally, a detailed case study involving battery prognostics demonstrates its use.

  11. Transplante de célula-tronco hematopoética para síndrome mielodisplásica Bone marrow transplantation in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Daniel G. Tabak

    2010-05-01

    Full Text Available As síndromes mielodisplásicas (SMD constituem um grupo de doenças hematológicas caracterizadas por citopenias crônicas, associadas a uma maturação celular anormal. A melhor forma de classificação atual destas patologias é o International Prognostic Scoring System (IPSS, que se baseia no grau de citopenia, número de mieloblastos na medula óssea e alterações citogenéticas. Há quatro estágios: baixo risco, riscos intermediário-1 e 2 e alto risco. Um grupo destes pacientes pode ser curado com o transplante de células-tronco hematopoéticas (TCTH. Esta forma de tratamento pode ser considerada para pacientes com idade inferior a 60 anos, que possuam um doador familiar HLA-idêntico. A opção por esta modalidade terapêutica depende de alguns critérios, que incluem o IPSS, o risco de progressão de doença, o risco de infecção e o estado geral do paciente. O TCTH autólogo pode ser considerado em pacientes que alcancem uma remissão completa citogenética e que não disponham de doador HLAidêntico. Em pacientes não candidatos ao TCTH mieloablativo, uma possibilidade é o transplante com regimes de intensidade reduzida. Estudos recentes têm demonstrado resultados favoráveis com esta opção terapêutica, pois, apesar do alto rico de recaída, as taxas de mortalidade associada ao procedimento são menores. Os pacientes com SMD devem ser dispostos em ensaios clínicos que considerem as comorbidades, DECH e riscos de recaída.The myelodysplastic syndrome (MDS encompasses a series of hematological conditions characterized by chronic cytopenias with abnormal cellular maturation. Based on the cytopenias, number of blast cells in bone marrow and cytogenetic abnormalities, MDS may be best classified by the International Prognostic Scoring System (IPSS in four groups: low risk, intermediate 1, intermediate 2 risks and high risk. A subset of patients can be cured following allogeneic hematopoietic stem cell transplantation (SCT. This

  12. Clinico-haematological characteristics in Pakistani patients of primary myelodysplastic syndrome according to World Health Organization classification.

    Science.gov (United States)

    Ehsan, Ayesha; Aziz, Mona

    2010-04-01

    To assess the applicability of WHO classification on a cohort of Pakistani myelodysplastic syndrome (MDS) patients, and determine their epidemiological and clinico-pathological features. Case series. Haematology Department, Shaikh Zayed Hospital, Lahore, from April 2004 to March 2006. Forty six patients of primary MDS diagnosed by World Health Organization (WHO) criteria were included in the study by nonprobability purposive sampling. The cohort was classified accordingly and the epidemiological, clinical and haematological parametres were assessed. Descriptive statistics were used to describe the data. Forty six patients (28 males and 18 females) of primary MDS were included in the study. The mean age was 46.21 years. According to the WHO classification, 12 cases of refractory anaemia, 24 cases of refractory cytopenia with multi lineage dysplasia, 1 case of refractory cytopenia with multi lineage dysplasia and ring sideroblasts, 3 cases of MDS unclassified and 3 cases each of refractory anaemia with excess of blasts I and II were diagnosed. Symptomatic anaemia was seen in 37 cases and pancytopenia was documented in 33 cases. Dyserythropoiesis affected 41 cases. Grade III reticulosis was seen in 7 cases. ALIP was present in 13 cases. MDS presented at a young age. Refractory cytopenia with multi lineage dysplasia was the dominant disease category. Further studies are suggested for identifying the cytogenetic abnormalities and del 5q- category.

  13. Durable Hematological and Major Cytogenetic Response in a Patient with Isolated 20q Deletion Myelodysplastic Syndrome Treated with Lenalidomide

    Directory of Open Access Journals (Sweden)

    Bagi Jana

    2014-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a clonal bone marrow disorder characterized by ineffective hematopoiesis. It is characterized by peripheral blood cytopenia and significant risk of progression to acute myeloid leukemia result. Deletion of the long arm of chromosome 20 (20q deletion is present in 3–7% of patients with MDS. Lenalidomide is an immunomodulatory agent with antiangiogenic activity. It is FDA approved for the treatment of anemia in patients with low or int-1 risk MDS with chromosome 5q deletion with or without additional cytogenetic abnormalities. Study of lenalidomide in patients with MDS without 5q deletion but other karyotypic abnormalities demonstrated meaningful activity in transfusion dependent patients; however, response of patients with isolated 20q deletion to lenalidomide is not known. We are reporting a patient with 20q deletion MDS treated with lenalidomide after he failed to respond to azacytidine; to our knowledge this is the first report of a patient with isolated 20q deletion treated with lenalidomide.

  14. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.

    Science.gov (United States)

    Kirschbaum, Mark; Gojo, Ivana; Goldberg, Stuart L; Bredeson, Christopher; Kujawski, Lisa A; Yang, Allen; Marks, Peter; Frankel, Paul; Sun, Xing; Tosolini, Alessandra; Eid, Joseph E; Lubiniecki, Gregory M; Issa, Jean-Pierre

    2014-10-01

    Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) may respond to treatment with epigenetic-modifying agents. Histone deacetylase inhibitors may synergize with hypomethylating agents. This phase 1 dose-escalation study was designed to determine the maximum tolerated dose, recommended phase 2 dose, safety and tolerability of vorinostat plus decitabine in patients with relapsed/refractory AML, newly-diagnosed AML, or intermediate- to high-grade MDS. Thirty-four patients received concurrent therapy with decitabine plus vorinostat and 37 received sequential therapy with decitabine followed by vorinostat. Twenty-nine patients had relapsed/refractory AML, 31 had untreated AML and 11 had MDS. The target maximum administered dose (MAD) of decitabine 20 mg/m(2) daily for 5 d plus vorinostat 400 mg/d for 14 d was achieved for concurrent and sequential schedules, with one dose-limiting toxicity (Grade 3 QTc prolongation) reported in the sequential arm. Common toxicities were haematological and gastrointestinal. Responses were observed more frequently at the MAD on the concurrent schedule compared with the sequential schedule in untreated AML (46% vs. 14%), relapsed/refractory AML (15% vs. 0%) and MDS (60% vs. 0%). Decitabine plus vorinostat given concurrently or sequentially appears to be safe and well-tolerated. Concurrent therapy shows promising clinical activity in AML or MDS, warranting further investigation. © 2014 John Wiley & Sons Ltd.

  15. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J

    2014-01-01

    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...

  16. In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome. A magnetic resonance imaging study

    DEFF Research Database (Denmark)

    Jensen, K E; Nielsen, H; Thomsen, C

    1989-01-01

    Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow...

  17. Cytogenetic prognostication within medulloblastoma subgroups.

    Science.gov (United States)

    Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

    2014-03-20

    Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

  18. Cytogenetic Prognostication Within Medulloblastoma Subgroups

    Science.gov (United States)

    Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

    2014-01-01

    Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

  19. [Marked hemosiderosis in myelodysplastic syndrome].

    Science.gov (United States)

    Klinz, C

    1999-01-29

    A 68-year-old man was admitted because of symptoms of lumbar pain. He was known to have chronic anemia with ring sideroblasts and diabetes melitus and to be in heart failure. Three months before he had been given 7 units of red cell concentrate. On admission the outstanding features were brown discoloration of the skin, absent body hair, tachycardia, hepatomegaly and small testicles. He had a normocytic anemia, hyperglycemia and raised transaminases, hypogonadism and vitamin D3 deficiency. The serum levels of iron, transferrin saturation and feritin were markedly elevated. Liver iron content/g dried liver was 4.2 g (by biomagnetometer). Radiology of the lumbar vertebrae showed osteoporosis and sonography confirmed hepatomegaly. The known myelodysplastic syndrome (MDS) had fed to secondary hemosiderosis with heart failure, liver involvement, diabetes mellitus, hypogonadism and osteoporosis. Symptomatic treatment was unsuccessfully complemented by desferoxamine (up to 4 g/12 h) to release iron. But very good iron excretion was then achieved with deferiprone (3 x 1 g/d). The patient later died of the sequelae of hemosiderosis. Even when they have not required transfusions, patients with long-standing MDS should be examined regularly for the possible development of secondary hemosiderosis so that iron-chelating agents can be administered as needed.

  20. Allogeneic stem cell transplantation for myelodysplastic syndromes: critical for cure?

    Science.gov (United States)

    de Witte, Theo

    2011-06-01

    Allogeneic stem cell transplantation (SCT) is the treatment of choice for young patients (age ≤ 55 years) with myelodysplastic syndromes (MDS) characterized by poor-risk or intermediate-risk cytogenetics, who have a histocompatible related or unrelated donor. For patients who lack an human leukocyte antigen-compatible donor, autologous SCT, or chemotherapy may be good alternatives for those with MDS and with good-risk cytogenetic characteristics. Iron toxicity is an underestimated cause of hematopoietic stem cell transplantation (HSCT) treatment-related mortality. The pathogenesis, diagnosis, and monitoring of iron-induced organ damage are currently topics of investigation. Prospective studies on the prevention or treatment of iron toxicity before HSCT and/or after HSCT are necessary. Copyright © 2011. Published by Elsevier Inc.

  1. Self-reported sleep disturbance and survival in myelodysplastic syndromes.

    Science.gov (United States)

    Luskin, Marlise R; Cronin, Angel M; Owens, Robert L; DeAngelo, Daniel J; Stone, Richard M; Wadleigh, Martha; Steensma, David P; Abel, Gregory A

    2017-05-01

    Neither the prevalence of sleep disturbance nor its association with fatigue and overall survival (OS) are well understood for patients with myelodysplastic syndromes (MDS). New patients at our institution (n = 251; 2006-2014) completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, which includes questions about sleep and fatigue. Fifty-three per cent reported at least 'a little' trouble sleeping. In multivariable models, anaemia and sleep disturbance were associated with fatigue (both P < 0·001). Additionally, in separate models, sleep disturbance (P = 0·002) and fatigue (P = 0·04) both predicted OS. Our data suggest that improving sleep quality may impact MDS-related fatigue and OS. © 2017 John Wiley & Sons Ltd.

  2. Differences in the distribution of subtypes according to the WHO classification 2008 between Japanese and German patients with refractory anemia according to the FAB classification in myelodysplastic syndromes.

    Science.gov (United States)

    Matsuda, Akira; Germing, Ulrich; Jinnai, Itsuro; Araseki, Kayano; Kuendgen, Andrea; Strupp, Corinna; Iwanaga, Masako; Miyazaki, Yasushi; Hata, Tomoko; Bessho, Masami; Gattermann, Norbert; Tomonaga, Masao

    2010-08-01

    We reported the different clinical features between Japanese and German refractory anemia (RA) patients in FAB classification. We re-analyzed the clinical features by WHO classification revised in 2008. The frequencies of refractory cytopenia with unilineage dysplasia (RCUD) and myelodysplastic syndrome-unclassified (MDS-U) with pancytopenia in Japanese patients were higher than in German patients (p<0.001). Refractory cytopenia with multilineage dysplasia patients showed the most unfavorable prognosis in both countries. The higher frequencies of MDS-U with pancytopenia and RCUD in Japanese patients may influence the different clinical characteristics between Japanese and German FAB-RA patients. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Bonou, Alexandra

    2012-01-01

    The core of the EU FP7 funded project W2Plastic is development of a magnetic density separation (MDS) of polyolefines in order to improve the sorting efficiency of these polymer types in different waste fractions. As