Stojanovikj, Aleksandar

Preferred name

Official Name

Stojanovikj, Aleksandar

Main Affiliation

aleksandar.stojanovikj@medf.ukim.edu.mk

Now showing 1 - 10 of 10

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Correlation of Somatic Mutations and Clinical Characteristics at Presentation in Patients with Essential Thrombocytemia
(American Society of Hematology, 2014-12-06)
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Popova-Simjanovska, Marija
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Ivanovski, Martin
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<jats:title>Abstract</jats:title> <jats:p>Background</jats:p> <jats:p>Most patients with essential thromocythemia (ET) have somatic mutations in janus kinase 2 (JAK2), calreticulin (CALR) and thrombopoietin receptor (MPL) genes. The clinical correlates at the presentation of patients with different mutations has not been established as yet.</jats:p> <jats:p>Materials and methods</jats:p> <jats:p>We evaluated the clinical, laboratory, and molecular features of 150 consecutive patients (93 females/57 males; average age 59,0+/- 14,2 years) with ET who were diagnosed at the University Clinic for Hematology in Skopje based on the revised WHO criteria. DNA from all patients was isolated from peripheral blood obtained at diagnosis using Qiagene DNA exctraction kit. The presence of JAK2V617F mutation was evaluated with fluorescent allele specific PCR/capillary electrophoresis. The CALR exon 9 insertions or deletions were initially detected with a fluorescent PCR/capillary electrophoresis and characterized with Sanger sequencing. The presence of mutations in exon 10 of the MPL gene was analyzed with direct sequencing of PCR amplified fragments. Informant consent was obtained from all participants. Statistical analysis was performed by Wilcoxon rank- sum test.</jats:p> <jats:p>Results</jats:p> <jats:p>The basic hematological parameters at diagnosis for all patients were as follows; Plt = 962.1x109 ±351,2 x109/L; Hb = 126,8 ±39,2 g/L; Le = 10,2x103 ±4,2 x103/µL. No correlation was found between any of these parameters and age at diagnosis or sex of the patients. JAK2V617F, CALR and MPL mutations were found in 89 (59.3%), 42 (28%) and 2 (1.3%) patients, respectively, while 17 (11.4%) patients did not have a mutation in the 3 evaluated genes (triple negative). Twelve different mutations were found in CALR gene, the most common being 52-bp deletion (c.1092_1143del) and 5-bp insertions (c.1154_1155insTTGTC) which were present in 11 (26,2%) and 20 (47,6%) patients, respectively. Ten different mutations, including 6 insertions (c.1088insTTGTC; c.1088delinsTTTGTC; c.1113_1123delinsTTGT; c.1154delinsTATGTC; c.1126_1131delinsTGCGT; c.1154_1155insGTGTC) and 4 deletions (c.1092_1137del; c.1096_1129del; c.1089_1141del; c.1100_1145del), were detected in the other 11 patients with CALR mutation. The JAK2V617F mutation and triple negative status were more prevalent in female patients (67% and 68% respectively), while no sex preference was detected in patients with the CALR mutation. The average age of patients with JAK2V617F, CALR insertions, CALR deletions and triple negative status were 60,7±13,9, 54,5±12,9, 59,0±15,1 and 58,8+/-14,8 years, respectively. Patients with CALR mutation had a higher platelet count at the time of diagnosis (1134x109 ±372,9 x 109 /L) compared to both patients with mutated JAK2 (952 x109 ±335,6 x109/L) (P=0.047) and to triple negative patients (mean 886 x109/L±303,2 x109/L) (P=0.024). Patients who carried CALR insertions had higher platelet counts (1222,9 ±396,8 x109/L) than patients with CALR deletions (mean 956,8 ±287,8 x109/L ) (P=0.0405). White blood cells counts were the highest in patients with JAK2V617F mutation (mean 11.1±4,5x103/µL) compared to both CALR positive (mean 8,8±2,7x103/µL) and triple negative patients (mean 7,9±2,2x103/µL) (P=0.0049). No difference in Hb levels were present between patients with various mutations.</jats:p> <jats:p>Conclussion</jats:p> <jats:p>ET patients with CALR insertions present with higher platelet counts and at an earlier age than patients with JAK2V617F, CALR deletions or triple negative patients, which might translate to differences in prognosis in these groups of patients. Higher incidence of JAK2V617F mutation and triple negative status in female patients point to a common mechanism for predisposition to these conditions.</jats:p> <jats:sec> <jats:title>Disclosures</jats:title> <jats:p>No relevant conflicts of interest to declare.</jats:p> </jats:sec>
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Diversities of Calreticulin Gene Mutations in Macedonian Patients With Essential Thrombocythemia
(Elsevier BV, 2016-08)
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Ivanovski, Martin
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Acquired calreticulin (CALR) gene mutations are one of the molecular hallmarks of essential thrombocythemia (ET). It has been suggested that patients with ET with CALR mutations are associated with a distinct clinical phenotype.
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Laparoscopic versus open splenectomy: a single center eleven-year experience
(Sestre milosrdnice University Hospital Center, 2013-06)
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Rusiti, Kemal
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The 11-year experience with open (OS) and laparoscopic (LS) splenectomy at a single center is reported. A total of 201 splenectomies were performed and clinical and demographic data were retrospectively analyzed. Patients were classified according to the type of operation as LS or OS. The mean age of patients was 45.1 +/- 17.1, and 141 patients were male. Out of 43 LS, 40 were done for hematologic causes, and they had a significantly shorter hospital stay compared to OS for hematologic causes (6.87 +/- 2.2 vs. 9.84 +/- 2.9 days; p = 0.000003) and significantly less requirement for blood transfusion (26.2 +/- 93.4 vs. 132.4 +/- 252.3 mL; p = 0.0152). In the OS group, comparison of patients with trauma and those with hematologic causes showed that significantly more males underwent surgery for trauma causes (35 of 43 vs. 16 of 21), hospital stay was longer (18.9 +/- 27.4 vs. 9.8 +/- 2.9 days) and blood requirement higher (708.1 +/- 603.7 mL vs. 132.4 +/- 252.3 mL; p = 0.0004, p = 0.047 and p = 0.000001, respectively). Laparoscopic splenectomy is a safe procedure for spleen removal.
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Role of Prognostic Nomogram and Survival Index in Prognosis and the Outcome of Patients with Chronic Lymphocytic Leukemia - A Single Center Experience
(Longdom Group SA, 2018)
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Cevreska L
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Ivanovski M
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Popova-Labachevska M
Introduction: Chronic lymphocytic leukemia (CLL) in its clinical course is a heterogeneous clonal lymphoproliferative disease. Some patients live without the need for therapy for decades, while in others the clinical course is aggressive. Research focuses on the identification of biological factors that affect this heterogeneity. Clinical systems for division by stages Rai and Binet cannot identify whether the patient will have an indolent or progressive course of the disease. At Texas University, "MD Anderson Cancer Center" with statistical analysis, several independent features have been identified that predict the overall survival and a model composed of several independent parameters with which patients are divided into 3 risk groups has been created. A nomogramprognostic model has been created that estimates the mean survival and predicts a probable total of five and ten years of survival using the six variables. Aim of the study: Evaluation of the applicability of the prognostic index and nomogram in terms of overall survival, prognosis in patients with CLL diagnosed and treated at the University's clinic for hematology in a period of ten years. Material and methods: The study is set up retrospectively and includes 300 patients with CLL diagnosed and treated at the University Clinic of Hematology for a period of 10 years. The CLL diagnosis was made according to the recommendations of the CLL International Working Group (IWCLL). Clinical stratification was done as part of the prognostic index, and the nomogram was implemented according to the RAI system. With the help of the prognostic index, patients were stratified into three prognostic risk groups (low, intermediate, high risk), and according to the prognostic nomogram, the median survival and the probable five and ten years total survival were assessed. Results: The multivariate Cox Proportional model has confirmed ECOG and ALC that they affect the overall survival time. The estimated mean-median probability of 5-year survival according to the prognostic nomogram in patients with CLL is 77.5%, and the estimated Probability for 10-year survival according to the prognosis nomogram is 50.0%. Conclusion: The evaluation determined that the prognostic index and nomogram are reproducible in patients with CLL diagnosed and treated in R. Macedonia. Characteristics that predict total survival and survival without therapy have been identified.
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Influence of Prognostic Factors on OverallSurvival in Myelodysplastic Syndromes
(ScopeMed, 2014-10)
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Accurate prediction of a patient's prognosis is useful to define the risk posed by the disease. Age, gender, peripheral blood cytopenia, proportion of bone marrow (BM) blasts, performance status, comorbidities, transfusion dependence, specific karyotype abnormalities and molecular biomarkers can refine the prediction of prognosis in MDS.
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INFLUENCE OF PROGNOSTIC FACTORS ON OVERALL SURVIVAL IN MYELODYSPLASTIC SYNDROMES
(Turkish Society of Hematology, 2015)
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Background: Accurate prediction of a patient’s prognosis is useful to define the risk posed by the disease. Age, gender, peripheral blood cytopenias, proportion of bone marrow (BM) blasts, performance status, comorbidities, transfusion dependence, specific karyotype abnormalities and molecular biomarkers can refine the prediction of prognosis in MDS. Aim: to assess the influence of the some prognostic factors like age, gender, cytopenias, BM blast percentage, transfusion dependence, ferritin, hemoglobin (Hb), lactate dehydrogenase (LDH), albumin and specific karyotype abnormalities in myelodysplastic syndromes on overall survival (OS). Patients and Methods: we retrospectively analyzed the cohort of 108 patients diagnosed between 1.1.2011 and 31.12.2013 at the University Clinic of Hematology, Ss Cyril and Methodius University, Skopje, Macedonia. They were evaluated for clinical and hematologic features at diagnosis and at leukemic transformation. Results: in the study group 62 were man and 46 women. Male to female ratio was 1.35 to 1. The differences in OS between men and women were significant (p =.03015). The mean age at diagnosis was 66,6 years. According to the age OS was 16,4 months. FAB subtypes influenced OS significantly (p =.03015). OS inversely correlated with BM blast percentage (p=.02327). Cytopenias had no impact on OS (p=.33755). Hb as a whole and groups with different levels of Hb had no influence on OS (p =.12142) and (p=.07535), respectively. The group with ferritin <500 μg/L had better OS (p=.04720). Transfusion dependence, LDH and albumin had no impact on OS. Leukemic transformation was noticed in 10 (9,3%) patients. Mortality was 36,1%. Conclusion: gender, FAB subtypes, BM blast percentage and the serum levels of ferritin had an influence on OS, while age, hemoglobin level, transfusion dependence, LDH and albumin had no impact on OS.
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Adverse effects of thalidomide administration, in patients with myeloma multiplex?
(ScopeMed, 2014-04)
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Cevreska, Lidija
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Myeloma multiplex is defined by the presence of monoclonal plasma cell population in the bone marrow>10%,M protein in the serum and/or urine ,and clinical evidence of end organ damage like hypercalcemia ,renal failure, anemia, or bone lesions. In the most hematologic malignancies the role of induction treatment is to achieve complete remission (CR). Thalidomide became a new therapeutic approach but use of Thalidomide as a single agent or combination with steroids or chemotherapy is associated with several side effects like deep vein thrombosis (DVT), peripheral neuropathy (PN), constipation, somnolence, pyrexia, pain, fatigue osteonecrosis of jaw, and teratogenicity that is the most worrying adverse event. Risk of appearance of DVT increased if we use combination of Thalidomide plus Dexamethasone plus cytotoxic chemotherapy such Cyclophosphamide. >30% DVT usually occurs during the first months of treatment and is more frequent in newly diagnosed patients with a high tumor burden. The second side effect is peripheral neuropathy (PN) which occurs in 50% of patients with MM treated with Thalidomide plus Dexamethasone and chemotherapy.
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CHROMOSOMAL ABNORMALITIES IN PHILADELPHIA CHROMOSOME- NEGATIVE CELLS IN PATIENT WITH CHRONIC MYELOGENOUS LEUKEMIA TREATED WITH FIRST GENERATION TYROSINE KINASE INHIBITOR- SINGLE CENTER EXPERIENCE
(Radiance Research Academy, 2013-05-10)
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Dukovski, Dushko
Chronic myelogenous leukemia (CML) is characterized by the presence of a Bcr-Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib as a selective inhibitor of Bcr-Abl induces complete cytogenetic remission in the majority of patients with CML in chronic phase. Targeted therapy of CML with imatinib favors the manifestation of Ph-(negative) clone disorders in some patients. Facts indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of complete remission. We report a case of a patient with CML, in chronic phase treated with imatinib which induces the most common abnormality trisomy 8.
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Reproductive Issues in Long-Term Surviving Patients following Therapy for Hodgkin’s Disease in the Republic of North Macedonia: Risks of Infertility According to First-Line Treatment Regimens
(MDPI AG, 2022-03-28)
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Infertility as a consequence of therapy presents a high psychosocial burden for HL patients. In the cohort of our analyzed patients, within the post-ABVD surviving patients, alterations of the spermogram were documented in a total of 6.1% of the male patients and 5.4% of the female patients developed amenorrhea. On the other hand, within the subgroup of surviving patients following BEACOPP chemotherapy, 60% of the male patients manifested defects in their spermogram, and as high as 28.6% of the female survivors reported loss of their monthly cycle. It has been reported on several occasions that even prior to treatment, the sperm of HL patients manifests poorer quality characteristics when analyzed against control specimens from healthy male donors. The analyzed results in ABVD-treated male HL patients confirm ABVD to be a safe regimen for males of all age categories, as well as for female patients under the age of thirty. In women above the age of 30, the infertility risk rate is relatively low (14%), which leaves the decision of preserving fertility to themselves. For all BEACOPP-treated female, as well as male patients, a consult with a reproductive medicine specialist is warranted prior to therapy, due to the high infertility risk, and the final decision should be made on an individual basis.
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Immunoblastic morphology as a possible prognostic indicator for the outcome of the patients with diffuse large B cell lymphoma in era of the rituximab based treatment: single centre experience
(Medip Academy, 2013-05)
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Dukovski, Dushko
Recently the results from one large prospective study indicated that immunoblastic morphology and not immunohistohemical features predict the outcome of the Diffuse large B lymphoma (DLBL). In order to investigate the prediction value of the immunoblastic morphology (IB) as a possible prognostic indicator for the outcome of our DLBL patient treated with the Rituximab (R)-CHOP regimen we conducted a retrospective study. Our study enrolled 192 DLBL patients diagnosed and treated at the University Clinic of Hematology in the period between February 2002 and December 2007. They were all treated with R-CHOP regimen and the median follow-up of the patient was 36 months. We analyzed the biopsy samples immunohistochemically for markers of germinal center (BCL6), postgerminal center (MUM1) and apoptosis (BCL2).The patients were categorized as DLBL(132; 68.7%), IB(60; 31.2). The median overall survival time (OS) were 59.3 months in DLBL group and 42.2 months in IB group, and time to treatment (TT) were 56.8 and 30.6 months respectively for the IB group. The DLBL and IB groups were comparable regarding the age, gender distributions and all others already established prognostic parameters as performance status, advanced IPI, albumin level except for the low IPI 0-2 which was statistically associated with the DLBL group (p=.024). Our results did not show any statistical survival advantage and better outcome for the patient classified as DLBL when treated with R-CHOP and indicate that immunohistohemical markers do not really reflect the molecular diversity of the tumor. Our work shows that IB morphology is a major risk factor in DLBL patients treated with RCHOP. Therefore this morphology appears to capture some adverse molecular events that a currently hard to detect with routine diagnostic procedures.

Stojanovikj, Aleksandar

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