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Browsing by Author "Tomin, Dragica (6603497854)"

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    Acute myocardial infarction during induction chemotherapy for acute MLL t(4;11) leukemia with lineage switch and extreme leukocytosis
    (2015)
    Čolović, Nataša (6701607753)
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    Bogdanović, Andrija (6603686934)
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    Virijević, Marijana (36969618100)
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    Vidović, Ana (6701313789)
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    Tomin, Dragica (6603497854)
    Introduction In patients with acute leukemias hemorrhage is the most frequent problem. Vein thrombotic events may appear rarely but arterial thromboses are exceptionally rare. We present a patient with acute leukemia and bilateral deep leg vein thrombosis who developed an acute myocardial infarction (AMI) during induction chemotherapy. The etiology and treatment of AMI in patients with acute leukemia, which is a rare occurrence, is discussed. Case Outline In April of 2012 a 37-year-old male presented with bilateral deep leg vein thrombosis and malaise. Laboratory data were as follows: Hb 118 g/L, WBC 354.109/L (with 91% blasts in differential leukocyte count), platelets 60.109/L. Bone marrow aspirate and immunophenotype revealed the presence of acute lymphoblastic leukemia. Cytogenetic analysis was as follows: 46,XY,t(4;11)(q21:q23) [2]/62-82,XY,t(4;11)[18]. Molecular analysis showed MLL-AF4 rearrangement. The patient was on low molecular weight heparin and combined chemotherapy according to protocol HyperCVAD. On day 10 after chemotherapy he got chest pain. Three days later AMI was diagnosed (creatine kinase 66 U/L, CK-MB 13U/L, troponin 1.19 μg/L). Electrocardiogram showed the ST elevation in leads D1, D2, aVL, V5 and V6 and “micro q” in D1. On echocardiography, hypokinesia of the left ventricle and ejection fraction of 39% was found. After recovering from AMI and restoring left ventricle ejection fraction to 59%, second course of HyperCVAD was given. The control bone marrow aspirate showed 88% of blasts but with monoblastic appearance. Flow cytometry confirmed a lineage switch from lymphoblasts to monoblasts. In further course of the disease he was treated with a variety of chemotherapeutic combinations without achieving remission. Eventually, palliative chemotherapy was administered to reduce the bulk of blasts. He died five months after the initial diagnosis. Conclusion AMI in young adults with acute leukemia is a very rare complication which may occur in patients with very high white blood cell count in addition with presence of a CD56 adhesion molecule and other concomitant thrombophilic factors. The treatment of AMI in patients with acute leukemias should include antiplatelet and anticoagulant therapy, even with more aggressive methods depending on patient’s age and clinical risk assessment. © 2015, Serbia Medical Society. All rights reserved.
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    Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom
    (2020)
    Janic, Dragana (15729368500)
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    Peric, Jelena (57402912400)
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    Karan-Djurasevic, Teodora (14035922800)
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    Kostic, Tatjana (57190702347)
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    Marjanovic, Irena (57189225697)
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    Stanic, Bojana (14026123900)
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    Pejanovic, Nadja (23486435300)
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    Dokmanovic, Lidija (15729287100)
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    Lazic, Jelena (7004184322)
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    Krstovski, Nada (24724852600)
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    Virijevic, Marijana (36969618100)
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    Tomin, Dragica (6603497854)
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    Vidovic, Ana (6701313789)
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    Suvajdzic Vukovic, Nada (7003417452)
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    Pavlovic, Sonja (7006514877)
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    Tosic, Natasa (15729686900)
    Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL). We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes. We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation. Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease. © 2019 Dragana Janic, Jelena Peric, Teodora Karan-Djurasevic, Tatjana Kostic, Irena Marjanovic, Bojana Stanic, Nadja Pejanovic, Lidija Dokmanovic, Jelena Lazic, Nada Krstovski, Marijana Virijevic, Dragica Tomin, Ana Vidovic, Nada Suvajdzic Vukovic, Sonja Pavlovic, Natasa Tosic, published by Sciendo.
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    Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom
    (2020)
    Janic, Dragana (15729368500)
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    Peric, Jelena (57402912400)
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    Karan-Djurasevic, Teodora (14035922800)
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    Kostic, Tatjana (57190702347)
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    Marjanovic, Irena (57189225697)
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    Stanic, Bojana (14026123900)
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    Pejanovic, Nadja (23486435300)
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    Dokmanovic, Lidija (15729287100)
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    Lazic, Jelena (7004184322)
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    Krstovski, Nada (24724852600)
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    Virijevic, Marijana (36969618100)
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    Tomin, Dragica (6603497854)
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    Vidovic, Ana (6701313789)
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    Suvajdzic Vukovic, Nada (7003417452)
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    Pavlovic, Sonja (7006514877)
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    Tosic, Natasa (15729686900)
    Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL). We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes. We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation. Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease. © 2019 Dragana Janic, Jelena Peric, Teodora Karan-Djurasevic, Tatjana Kostic, Irena Marjanovic, Bojana Stanic, Nadja Pejanovic, Lidija Dokmanovic, Jelena Lazic, Nada Krstovski, Marijana Virijevic, Dragica Tomin, Ana Vidovic, Nada Suvajdzic Vukovic, Sonja Pavlovic, Natasa Tosic, published by Sciendo.
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    Clinical significance of genetic aberrations in secondary acute myeloid leukemia
    (2012)
    Milosevic, Jelena D. (57210734797)
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    Puda, Ana (54785191600)
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    Malcovati, Luca (6602486656)
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    Berg, Tiina (23488040400)
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    Hofbauer, Michael (55330363600)
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    Stukalov, Alexey (24766530300)
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    Klampfl, Thorsten (36570502300)
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    Harutyunyan, Ashot S. (36570218100)
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    Gisslinger, Heinz (7005768562)
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    Gisslinger, Bettina (6507974358)
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    Burjanivova, Tatiana (13605242300)
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    Rumi, Elisa (6602625071)
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    Pietra, Daniela (35562732200)
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    Elena, Chiara (15049389800)
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    Vannucchi, Alessandro M. (7005217248)
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    Doubek, Michael (7003925108)
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    Dvorakova, Dana (57190091364)
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    Robesova, Blanka (35176411600)
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    Wieser, Rotraud (7005738645)
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    Koller, Elisabeth (7006030226)
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    Suvajdzic, Nada (7003417452)
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    Tomin, Dragica (6603497854)
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    Tosic, Natasa (15729686900)
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    Colinge, Jacques (7005700195)
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    Racil, Zdenek (6507522751)
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    Steurer, Michael (35206859600)
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    Pavlovic, Sonja (7006514877)
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    Cazzola, Mario (34667651300)
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    Kralovics, Robert (6602709918)
    The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% ± 9.4% vs. 35.4% ± 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.33-5.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms. © 2012 Wiley Periodicals, Inc.
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    Dipeptidyl peptidase IV: Serum activity and expression on lymphocytes in different hematological malignancies
    (2013)
    Matić, Ivana Z. (36572349500)
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    Dordević, Milica (43760989500)
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    Dordić, Marija (57193949676)
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    Grozdanić, Nada (55318801700)
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    Damjanović, Ana (7004519598)
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    Kolundžija, Branka (55319359400)
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    Vidović, Ana (6701313789)
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    Bila, Jelena (57208312102)
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    Ristić, Slobodan (35300292100)
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    Mihaljević, Biljana (6701325767)
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    Tomin, Dragica (6603497854)
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    Milanović, Nenad (6603846814)
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    Ristić, Dušan (8869432800)
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    Purić, Mila (55920136000)
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    Gavrilović, Dušica (8849698200)
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    Cordero, Oscar J. (7004437937)
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    Juranić, Zorica D. (7003932917)
    The aim of this research was to determine the serum dipeptidyl peptidase IV (DPPIV) activity as well as the percentages of CD26 + lymphocytes and CD26 + overall white blood cells in patients with hematological malignancies: non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), leukemia, plasmacytoma and multiple myeloma, and in healthy individuals. Data from our study showed significantly decreased serum DPPIV activity and a significant decrease in the percentage of: CD26 + lymphocytes, CD26 + overall white blood cells and lymphocytes in patients with NHL in comparison to healthy controls. Patients with leukemia had a statistically significant lower activity of DPPIV in serum and significant decrease in the percentage of CD26 + lymphocytes in relation to healthy controls. Furthermore, significantly decreased DPPIV serum activity associated with a significantly reduced percentage of CD26 + overall white blood cells and percentage of lymphocytes was found in patients with multiple myeloma when compared to the healthy control group. The obtained results indicate that immune disturbances that can occur in hematological malignancies might be related to the decreased expression and activity of CD26/DPPIV that we observed. © 2013 Informa UK, Ltd.
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    Dipeptidyl peptidase IV: Serum activity and expression on lymphocytes in different hematological malignancies
    (2013)
    Matić, Ivana Z. (36572349500)
    ;
    Dordević, Milica (43760989500)
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    Dordić, Marija (57193949676)
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    Grozdanić, Nada (55318801700)
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    Damjanović, Ana (7004519598)
    ;
    Kolundžija, Branka (55319359400)
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    Vidović, Ana (6701313789)
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    Bila, Jelena (57208312102)
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    Ristić, Slobodan (35300292100)
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    Mihaljević, Biljana (6701325767)
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    Tomin, Dragica (6603497854)
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    Milanović, Nenad (6603846814)
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    Ristić, Dušan (8869432800)
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    Purić, Mila (55920136000)
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    Gavrilović, Dušica (8849698200)
    ;
    Cordero, Oscar J. (7004437937)
    ;
    Juranić, Zorica D. (7003932917)
    The aim of this research was to determine the serum dipeptidyl peptidase IV (DPPIV) activity as well as the percentages of CD26 + lymphocytes and CD26 + overall white blood cells in patients with hematological malignancies: non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), leukemia, plasmacytoma and multiple myeloma, and in healthy individuals. Data from our study showed significantly decreased serum DPPIV activity and a significant decrease in the percentage of: CD26 + lymphocytes, CD26 + overall white blood cells and lymphocytes in patients with NHL in comparison to healthy controls. Patients with leukemia had a statistically significant lower activity of DPPIV in serum and significant decrease in the percentage of CD26 + lymphocytes in relation to healthy controls. Furthermore, significantly decreased DPPIV serum activity associated with a significantly reduced percentage of CD26 + overall white blood cells and percentage of lymphocytes was found in patients with multiple myeloma when compared to the healthy control group. The obtained results indicate that immune disturbances that can occur in hematological malignancies might be related to the decreased expression and activity of CD26/DPPIV that we observed. © 2013 Informa UK, Ltd.
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    Favorable outcome of hepatosplenic candidiasis in a patient with acute leukemia
    (2015)
    Čolović, Nataša (6701607753)
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    Arsenijević, Valentina Arsić (6507940363)
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    Suvajdžić, Nada (7003417452)
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    Djunić, Irena (23396871100)
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    Tomin, Dragica (6603497854)
    Introduction Acute leukemias treatment requires strong chemotherapy. Patients that develop bone marrow aplasia become immunocompromised, thus becoming liable to bacterial and fungal infections. Fungal infections caused by Candida are frequent. Hepatosplenic candidiasis (HSC) is a frequent consequence of invasive candidiasis which is clinically presented with prolonged febrility unresponsive to antibiotics. Case Outline A 53-year-old patient with acute myeloid leukemia was submitted to standard chemotherapy “3+7” regimen (daunoblastine 80 mg i.v. on days 1 to 3, cytarabine 2×170 mg i.v. during 7 days) and achieved complete remission. However, during remission he developed febrility unresponsive to antibiotics. Computerised tomography (CT) of the abdomen showed multiple hypodense lesions within the liver and spleen. Haemocultures on fungi were negative. However, seroconversion of biomarkers for invasive fungal infection (IFI) (Candida and Aspergillus antigen/Ag and antibody/Ab) indicated possible HSC. Only high positivity of anti-Candida IgG antibodies, positivity of mannan and CT finding we regarded sufficient for the diagnosis and antimycotic therapy. Three months of treatment with different antimycotics were necessary for complete disappearance of both clinical symptoms and CT findings. Conclusion In patients with prolonged febrile neutropenia IFI has to be strongly suspected. If imaging techniques show multiple hypodense lesions within liver and spleen, HSC has to be taken seriously into consideration. We believe that, along with CT finding, positive laboratory Candida biomarkers (mannan and IgG antibodies) should be considered sufficient for “probable HSC” and commencement of antifungal therapy, which must be long enough, i.e. until complete disappearance of clinical symptoms and CT findings are achieved. © 2015, Serbia Medical Society.
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    Hypercalcemia with multiple osteolytic lesions and increased circulating tumor necrosis factor in an adult patient with B-cell acute lymphoblastic leukemia
    (2016)
    Virijević, Marijana (36969618100)
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    Vidović, Ana (6701313789)
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    Čolović, Nataša (6701607753)
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    Djunić, Irena (23396871100)
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    Mitrović, Mirjana (54972086700)
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    Suvajdžić-Vuković, Nada (7003417452)
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    Tomin, Dragica (6603497854)
    Introduction Acute lymphoblastic leukemia (ALL) is very rarely presented with diffuse osteolytic lesions and hypercalcemia. Case Outline We report a 28-year-old male with the B-cell ALL who presented with extensive osteolytic lesions, bone pain, hepatosplenomegaly, and pancytopenia without circulating blasts in peripheral blood. An increased serum level of tumor necrosis factor (TNF-α) was registered while the levels of IL-1α and IL-1β were normal. The patient failed to achieve remission on two induction regimens but achieved one after the successful allogeneic stem cell transplantation, which lasted for six months, after which he developed a relapse and died. Conclusion The presented case may serve as a clinical demonstration of possible involvement of TNF-α as a pathogenic factor in the evolution of osteolytic lesions that are occasionally observed in patients with ALL. This might have relevance in the management of such patients as chemotherapy alone may not represent the beneficial option in this clinical context. © 2016, Serbia Medical Society. All rights reserved.
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    Incidence and mortality patterns of acute myeloid leukemia in Belgrade, Serbia (1999-2013)
    (2018)
    Maksimovic, Natasa (12772951900)
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    Zaric, Milica (56786047800)
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    Gazibara, Tatjana (36494484100)
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    Trajkovic, Goran (9739203200)
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    Maric, Gorica (56433592800)
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    Miljus, Dragan (24169622800)
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    Vukovic, Nada Suvajdzic (36446767400)
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    Tomin, Dragica (6603497854)
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    Virijevic, Marijana (36969618100)
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    Tepavcevic, Darija Kisic (57218390033)
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    Pekmezovic, Tatjana (7003989932)
    Introduction: To assess incidence and mortality trends of acute myeloid leukemia (AML) in Belgrade (Serbia) in a 15-year period (from 1999 to 2013). Material and Methods: Data were obtained from the Cancer Registry of Serbia, Institute of Public Health of Serbia. Standardized incidence and mortality rates per 100,000 inhabitants were calculated by direct standardization method using World Standard Population. Analysis of raw data indicated single-digit numbers per year and per 5-year age cohorts. Therefore, we merged years of diagnosis to three-year intervals, creating so-called “moving averages”. We also merged study population to 10-year age cohorts. Results: Both incidence and mortality rates increased with age, i.e., the lowest rates were observed in the youngest age groups and the highest rates were observed in oldest age groups. In all age groups, except the youngest (15-24 years), AML incidence was statistically significantly higher in men compared with women. Average age-adjusted incidence was 2.73/100,000 (95% confidence interval (CI) 2.28-3.71). Average age-adjusted mortality was 1.81/100,000 (95% CI 1.30-2.26). Overall, there were no significant changes in incidence trend. Age-adjusted incidence rates had increasing tendency among men aged 65-74 years (B = 0.80, standard error (SE) = 0.11; p = 0.005) and in total population aged 65-74 years (B = 0.41, SE = 0.09; p = 0.023). Increasing tendency in incidence of AML among women was observed in age group >75 years (B = 0.63, SE = 0.14; p = 0.019). No changes of mortality trend were observed. Conclusion: There was no significant change in trends of AML from 1999 to 2013 in the population of Belgrade. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
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    Induction chemotherapy versus palliative treatment for acute myeloid leukemia in a consecutive cohort of elderly patients
    (2012)
    Colovic, Milica (21639151700)
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    Colovic, Natasa (6701607753)
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    Radojkovic, Milica (57197430605)
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    Stanisavljevic, Dejana (23566969700)
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    Kraguljac, Nada (6602690529)
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    Jankovic, Gradimir (7005387173)
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    Tomin, Dragica (6603497854)
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    Suvajdzic, Nada (7003417452)
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    Vidovic, Ana (6701313789)
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    Atkinson, Henry Dushan (7101883648)
    A retrospective survey of 210 consecutive patients aged ≥65 years (median age 69 years, range 65- 88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/ 172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p00.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p00.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p00.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p00.000, CI 95 % 2.209-3.458), absence of splenomegaly (p00.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p0 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p00.000), the ECOG PS (p00.045) and the ECOG PS (p00.000), and HCT-CI (p00.000) in the NIC group of elderly patients. The present study suggests that a subgroup of elderly patients with both ECOG PS and HCT-CI≤2 at presentation may be eligible for intensive induction chemotherapy. © 2012 Springer-Verlag.
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    International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation ≥6: A new predictor of hemorrhagic early death in acute promyelocytic leukemia
    (2013)
    Mitrovic, Mirjana (54972086700)
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    Suvajdzic, Nada (7003417452)
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    Bogdanovic, Andrija (6603686934)
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    Kurtovic, Nada Kraguljac (36195445000)
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    Sretenovic, Aleksandra (24170024700)
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    Elezovic, Ivo (12782840600)
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    Tomin, Dragica (6603497854)
    High-hemorrhagic early death (ED) rate is a major impediment in the managing of acute promyelocytic leukemia (APL). In our group of 56 newly diagnosed APL patients, ED occurred in 12 subjects, due to endocranial bleeding (8/12), differentiation syndrome (2/12), or infection (2/12). Predictors of hemorrhagic ED were as follows: white blood cells count ≥20 × 10 9/L (P = 0.002337), Eastern cooperative oncology group performance status ≥3 (P = 0.00173), fibrinogen level <2 g/L (P = 0.004907), prothrombin time <50% (P = 0.0124), and International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation (ISTH DIC score) ≥6 (P = 0.00741). Multivariate analysis indicated ISTH DIC score ≥6 to be the most significant predictor for hemorrhagic ED (P = 0.008). The main finding of this study is that simple coagulation-related tests, performed on hospital admission and combined in the ISTH DIC score, might help to identify patients at high risk for fatal bleeding needing more aggressive supportive measures. © 2013 Springer Science+Business Media New York.
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    International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation ≥6: A new predictor of hemorrhagic early death in acute promyelocytic leukemia
    (2013)
    Mitrovic, Mirjana (54972086700)
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    Suvajdzic, Nada (7003417452)
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    Bogdanovic, Andrija (6603686934)
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    Kurtovic, Nada Kraguljac (36195445000)
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    Sretenovic, Aleksandra (24170024700)
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    Elezovic, Ivo (12782840600)
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    Tomin, Dragica (6603497854)
    High-hemorrhagic early death (ED) rate is a major impediment in the managing of acute promyelocytic leukemia (APL). In our group of 56 newly diagnosed APL patients, ED occurred in 12 subjects, due to endocranial bleeding (8/12), differentiation syndrome (2/12), or infection (2/12). Predictors of hemorrhagic ED were as follows: white blood cells count ≥20 × 10 9/L (P = 0.002337), Eastern cooperative oncology group performance status ≥3 (P = 0.00173), fibrinogen level <2 g/L (P = 0.004907), prothrombin time <50% (P = 0.0124), and International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation (ISTH DIC score) ≥6 (P = 0.00741). Multivariate analysis indicated ISTH DIC score ≥6 to be the most significant predictor for hemorrhagic ED (P = 0.008). The main finding of this study is that simple coagulation-related tests, performed on hospital admission and combined in the ISTH DIC score, might help to identify patients at high risk for fatal bleeding needing more aggressive supportive measures. © 2013 Springer Science+Business Media New York.
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    Mucormycosis of the paranasal sinuses in a patient with acute myeloid leukemia
    (2016)
    Čolović, Nataša (6701607753)
    ;
    Arsić-Arsenijević, Valentina (6507940363)
    ;
    Barać, Aleksandra (55550748700)
    ;
    Suvajdžić, Nada (7003417452)
    ;
    Leković, Danijela (36659562000)
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    Tomin, Dragica (6603497854)
    Introduction Invasive fungal infection is among the leading causes of morbidity, mortality, and economic burden for patients with acute leukemia after induction of chemotherapy. In the past few decades, the incidence of invasive fungal infection has increased dramatically. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. Mucorales). Neutropenic patients are at a high risk of developing an invasive mucormycosis with fulminant course and high mortality rate (35–100%). Case Outline We are presenting the case of a 72-year-old male with an acute monoblastic leukemia. The patient was treated during five days with hydroxycarbamide 2 × 500 mg/day, followed by cytarabine 2 × 20 mg/sc over the next 10 days. He developed febrile neutropenia, headache, and edema of the right orbital region of the face. Computed tomography of the sinuses revealed shadow in sinuses with thickening of mucosa of the right paranasal sinuses. Lavage and aspirate from the sinuses revealed Rhizopus oryzae. Mucormycosis was successfully treated with amphotericin B (5 mg/kg/day) followed by ketoconazole (400 mg/day). Two months later the patient died from primary disease. Conclusion In patients with acute leukemia who developed aplasia, febrile neutropenia, and pain in paranasal sinuses, fungal infection should be taken into consideration. New and non-invasive methods for taking samples from sinuses should be standardized in order to establish an early and accurate diagnosis of mucormycosis with the source in paranasal sinuses, and to start early treatment by a proper antifungal drug. Clear communication between physician and mycologist is critical to ensure proper and timely sampling of lavage and aspirate from sinuses and correct specimen processing when mucormycosis is suspected clinically. ©2016, Serbia Medical Society. All rights reserved.
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    Peripartum cardiomyopathy in a patient treated for acute myeloid leukemia
    (2016)
    Čolović, Nataša (6701607753)
    ;
    Seferović, Petar (6603594879)
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    Plećić, Miroslava (57188634991)
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    Vidović, Ana (6701313789)
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    Suvajdžić, Nada (7003417452)
    ;
    Tomin, Dragica (6603497854)
    Introduction Peripartum cardiomyopathy usually presents with systolic heart failure during the last months of pregnancy and up to five months postpartum. The disease is rare and can be fatal. Case Outline We report a 30-year-old female who was diagnosed with acute myeloid leukemia, with maturation and cytogenetic finding of t(8;21)(q22;q22),del(9)(q22) in January 2004. She was treated with chemotherapy and achieved complete remission that lasts to date. She became pregnant and delivered a healthy newborn with caesarean section in 2009. Seven months later, she again became pregnant and delivered the second child with caesarean section in January 2011. Seven days after delivery she developed symptoms and signs of heart failure. Electrocardiogram showed sinus rhythm, low voltage and negative T-waves in inferior and lateral leads. Echocardiography revealed global left ventricular dysfunction with ejection fraction of 15%, with mobile thrombotic mass of 12 mm attached to the left ventricle wall. She was treated with both unfractionated and low-molecular heparin, diuretics, cardiotonics, and beta-blockers. Within six following weeks left ventricle systolic function improved up to 25–30%. The full clinical recovery was achieved in September 2013, resulting in absence of heart failure and left ventricular ejection fraction of 54%. Conclusion Peripartum cardiomyopathy is a rare condition. The cause of cardiomyopathy is unknown, but it is believed that it could be triggered by various conditions and risk factors. Although the patient was treated with cardiotoxic drugs (doxorubicin and mitoxantrone) in permitted doses, they could have been contributory factors of myocardial damage. Close monitoring of cardiac function in the peripartal period might be beneficial in patients treated with cardiotoxic drugs. © 2016, Serbia Medical Society. All rights reserved.
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    Pretreatment risk factors and importance of comorbidity for overall survival, complete remission, and early death in patients with acute myeloid leukemia
    (2012)
    Djunic, Irena (23396871100)
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    Virijevic, Marijana (36969618100)
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    Novkovic, Aleksandra (36969484900)
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    Djurasinovic, Vladislava (35172762900)
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    Colovic, Natasa (6701607753)
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    Vidovic, Ana (6701313789)
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    Suvajdzic-Vukovic, Nada (7003417452)
    ;
    Tomin, Dragica (6603497854)
    The objective of this single-center study was to determine the pretreatment risk factors and influence of comorbidity on outcome in patients with acute myeloid leukemia (AML). The research involved 145 patients with AML during a 58-month follow-up period. The results suggest that the most significant predictor of poor overall survival (OS) is an adverse karyotype (P = 0.007), while for poor rate of complete remission (CR) it is age ≥55 years, and for early death the most significant predictor is comorbidity, as scored by the Hematopoetic Cell Transplantation Comorbidity Index (HCT-CI), P = 0.001. When we divided the patients into two groups: aged ≥55 years and aged <55 years, these predictors differed. In the group aged ≥55 years the most significant predictor of OS (P = 0.013) and for early death (P = 0.003) was HCT-CI (P = 0.013), while in the younger group it was karyotype (P < 0.001). The most significant predictor of CR in the elderly was increased serum lactate dehydrogenase (LDH) level (P = 0.045). In the younger patients, the most significant predictor of CR was leukocytosis (P = 0.001) and for early death it was infection as the comorbidity (P = 0.007). We point out the importance of comorbidity for OS and early death, as well as the impact of infection in patients with AML. © W.S. Maney & Son Ltd 2012.
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    Prognostic impact of NPM1 mutations in serbian adult patients with acute myeloid leukemia
    (2012)
    Kuzmanovic, Milos (6602721300)
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    Tosic, Natasa (15729686900)
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    Colovic, Natasa (6701607753)
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    Karan-Djurasevic, Teodora (14035922800)
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    Spasovski, Vesna (26655022200)
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    Radmilovic, Milena (56554098500)
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    Nikcevic, Gordana (6602344117)
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    Suvajdzic-Vukovic, Nada (7003417452)
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    Tomin, Dragica (6603497854)
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    Vidovic, Ana (6701313789)
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    Virijevic, Marijana (36969618100)
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    Pavlovic, Sonja (7006514877)
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    Colovic, Milica (21639151700)
    Based on current findings, the presence of NPM1 mutations in acute myeloid leukemia (AML) patients is associated with an increased probability of complete remission (CR) and better overall survival (OS). We determined the incidence and prognostic relevance of NPM1 mutations, their association with FLT3 and IDH mutations, and other clinical characteristics in Serbian adult AML patients. Samples from 111 adult de novo AML patients, including 73 AML cases with a normal karyotype (NK-AML), were studied. NPM1, FLT3, and IDH mutations were detected by PCR and direct sequencing. NPM1 mutations were detected in 22.5% of patients. The presence of NPM1 mutations predicted a low CR rate and shorter OS. NPM1 mutations showed an association with both FLT3 and IDH mutations. Survival analysis based on NPM1/FLT3 mutational status revealed a lower OS for NPM1 +/FLT3- compared to the NPM1-/FLT3- group in NK-AML patients. The lack of impact or unfavorable prognostic effect of NPM1 mutations found in this study can be assigned to a small cohort of analyzed AML patients, as can the presence of FLT3 and IDH mutations or other genetic lesions that cooperate with NPM1 mutations influencing prognosis. Copyright © 2012 S. Karger AG, Basel.
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    Prognostic risk score for the survival of elderly patients with acute myeloid leukaemia comprising comorbidities
    (2013)
    Djunic, Irena (23396871100)
    ;
    Suvajdzic-Vukovic, Nada (7003417452)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Novkovic, Aleksandra (36969484900)
    ;
    Colovic, Natasa (6701607753)
    ;
    Vidovic, Ana (6701313789)
    ;
    Tomin, Dragica (6603497854)
    Using various risk factor scores, we aimed to identify a subset of elderly patients with acute myeloid leukaemia (AML) for whom it was possible to assess the prognosis. We also aimed to develop a novel prognostic score system. This single centre study involved 102 patients of ≥60 years of age with non-promyelocytic AML. The adverse cytogenetic risk group appeared as the most significant independent prognostic factor for overall survival (OS). Our prognostic scoring system was developed after analysing prognostic risk factors and was applied for patients with favourable and intermediate (I and II) cytogenetic risk groups: age <65 years of age, normal lactate dehydrogenase (LDH) and a comorbidity score obtained applying the haematopoietic cell transplantation-specific comorbidity index (HCT-CI) < 3 = 0 points, in which age ≥65 years = 1 point and an elevated LDH score and HCT-CI ≥3 = 2 points. According to this prognostic model, patients without adverse cytogenetics were classified into three risk groups: favourable = 0-2 points, intermediate = 3-4 points and poor = > 4 points. The OS between these groups was highly significant (p < 0.001). The prognostic model developed in this study may refine the prognosis procedure of elderly AML patients without an adverse karyotype regarding OS, thereby guiding the treatment approach. © 2012 Springer Science+Business Media New York.
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    Prognostic risk score for the survival of elderly patients with acute myeloid leukaemia comprising comorbidities
    (2013)
    Djunic, Irena (23396871100)
    ;
    Suvajdzic-Vukovic, Nada (7003417452)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Novkovic, Aleksandra (36969484900)
    ;
    Colovic, Natasa (6701607753)
    ;
    Vidovic, Ana (6701313789)
    ;
    Tomin, Dragica (6603497854)
    Using various risk factor scores, we aimed to identify a subset of elderly patients with acute myeloid leukaemia (AML) for whom it was possible to assess the prognosis. We also aimed to develop a novel prognostic score system. This single centre study involved 102 patients of ≥60 years of age with non-promyelocytic AML. The adverse cytogenetic risk group appeared as the most significant independent prognostic factor for overall survival (OS). Our prognostic scoring system was developed after analysing prognostic risk factors and was applied for patients with favourable and intermediate (I and II) cytogenetic risk groups: age <65 years of age, normal lactate dehydrogenase (LDH) and a comorbidity score obtained applying the haematopoietic cell transplantation-specific comorbidity index (HCT-CI) < 3 = 0 points, in which age ≥65 years = 1 point and an elevated LDH score and HCT-CI ≥3 = 2 points. According to this prognostic model, patients without adverse cytogenetics were classified into three risk groups: favourable = 0-2 points, intermediate = 3-4 points and poor = > 4 points. The OS between these groups was highly significant (p < 0.001). The prognostic model developed in this study may refine the prognosis procedure of elderly AML patients without an adverse karyotype regarding OS, thereby guiding the treatment approach. © 2012 Springer Science+Business Media New York.
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    Prognostic significance of CD56 antigen expression in patients with acute myeloid leukemia
    (2012)
    Djunic, Irena (23396871100)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Djurasinovic, Vladislava (35172762900)
    ;
    Novkovic, Aleksandra (36969484900)
    ;
    Colovic, Natasa (6701607753)
    ;
    Kraguljac-Kurtovic, Nada (37037758700)
    ;
    Vidovic, Ana (6701313789)
    ;
    Suvajdzic-Vukovic, Nada (7003417452)
    ;
    Tomin, Dragica (6603497854)
    The aims of this study were to investigate the frequency and prognostic relevance of CD56 expression in patients with acute myeloid leukemia (AML) and to compare the importance of CD56 expression with standard prognostic factors, such as age, leukocytosis, cytogenetic abnormalities and performance status. We analyzed the data of 184 newly diagnosed patients with non-promyelocytic AML and a follow-up of 36 months. The median patient age was 58 years, with a range of 18-79. CD56+ antigen was recorded in 40 patients (21.7%). CD56 + was the most significant risk factor for OS: P = 0.05. The most significant factor for a poor rate of CR was age ≥ 55 years (P = 0.001). CD56 positivity had no significant influence on CR rate, but it was the most significant risk factor for disease-free survival (P = 0.005). The CD56 antigen is an independent prognostic risk factor, and its presence should be measured regularly for a better prognostic assessment of patients with AML. Copyright © Springer Science+Business Media, LLC 2011.
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    Prognostic significance of CD56 antigen expression in patients with acute myeloid leukemia
    (2012)
    Djunic, Irena (23396871100)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Djurasinovic, Vladislava (35172762900)
    ;
    Novkovic, Aleksandra (36969484900)
    ;
    Colovic, Natasa (6701607753)
    ;
    Kraguljac-Kurtovic, Nada (37037758700)
    ;
    Vidovic, Ana (6701313789)
    ;
    Suvajdzic-Vukovic, Nada (7003417452)
    ;
    Tomin, Dragica (6603497854)
    The aims of this study were to investigate the frequency and prognostic relevance of CD56 expression in patients with acute myeloid leukemia (AML) and to compare the importance of CD56 expression with standard prognostic factors, such as age, leukocytosis, cytogenetic abnormalities and performance status. We analyzed the data of 184 newly diagnosed patients with non-promyelocytic AML and a follow-up of 36 months. The median patient age was 58 years, with a range of 18-79. CD56+ antigen was recorded in 40 patients (21.7%). CD56 + was the most significant risk factor for OS: P = 0.05. The most significant factor for a poor rate of CR was age ≥ 55 years (P = 0.001). CD56 positivity had no significant influence on CR rate, but it was the most significant risk factor for disease-free survival (P = 0.005). The CD56 antigen is an independent prognostic risk factor, and its presence should be measured regularly for a better prognostic assessment of patients with AML. Copyright © Springer Science+Business Media, LLC 2011.
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