Faculty of Medicine

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    Preliminary results of introducing the method multiparameter flow cytometry in patients with acute leukemia in Republic of Macedonia
    (ID Design 2012/DOOEL Skopje, 2008-12-05)
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    Hadzi-Pecova, Liljana
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    Abstract Background. In this paper we present the initial results of introducing the method of multiparameter flow cytometry (MPF) in patients with acute leukemia in the Republic of Macedonia. Aim. The aim of our study is to improve the diagnosis and management of acute leukemia, to establish the correct lineage assignment of the blast cells and to select effective treatment strategy for each single acute leukemia patient. Material and methods. A total of 44 adult (>15 years) patients (from initially 45 tested) with acute leukemia who were consecutively admitted at the Clinic of Hematology-Skopje from January through June 2008, were enrolled in this study. The MPF was introduced for the first time in the Republic of Macedonia and was performed at the Institute for Immunobiology and Human Genetics, Faculty of Medicine-Skopje. Results. Our results showed that morphology and cytochemistry established lineage in 39 of patients, but not in 5 cases that presented as acute leukemia, of which 4 were assigned as myeloid and in one nonhematopoietic malignancy was indicated. Furthermore immunophenotyping change the lineage assigned based on morphology and cytochemistry in one case from lymphoid to myeloid. Results from our study showed that routine immunophenotyping improved the diagnosis in 6 (13.3%) cases. The exact lineage assignment of the blasts cells guides to implementation of specific molecular analyses in some subtypes of acute leukemia and their further definition, which is essential for more appropriate single patient therapeutic decisions. Conclusion. Our data support routine implementation of MPF in the diagnostic evaluation of acute leukemia.
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    Minimal screening analysis based algorithm for diagnosis and clinical stratification of patients with acute myeloid leukaemia (AML): single centre experience
    (Macedonian Academy of Sciences and Arts, 2012-07)
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    Ivanovski, Martin
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    Hadzi-Pecova, Liljana
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    Dukovski, Dushko
    A b s t r a c t: In this paper we present our results from a study designed in order to establish and standardize a diagnostic algorithm for acute myeloid leukaemia (AML) in the Republic of Macedonia. A total of 146 consecutive adult patients (> 15 years) were enrolled in the study. First, we determined the correct lineage assignment of the blast cells and evaluated the incidence of the favourable PML/RARα, AML1/ETO, CBFβ/MYH11 genetic markers among the AML cases. Additionally, the obtained results were correlated with patients’ age, comorbidities, and performance status, and each single AML patient was stratified to effective treatment strategy. Our results showed that morphology and cytochemistry established a lineage in 132 (89.1%) of the patients, but not in 16 cases that presented as acute leukaemia, of which 7 were assigned as myeloid, and in two a non-haematopoietic malignancy was indicated with immunophenotyping. Mulitparameter flow cytometry immunophenotyping also changed the assigned lineage based on morphology and cytochemistry in 5 (3.3%) of the patients from lymphoid to myeloid and improved diagnosis in 21 (14.1%) cases. By using a reverse transcriptase-polymerase chain reaction (RT-PCR) essay 28 (23.1%) patients were classified in the prognostically favourable AML genetic group; 8 patients expressed the fusion transcript PML/RARα, 5 AML1/ETO and 15 CBFβ/MYH11. Moreover, analyses of the age, performance status and comorbidities further stratified an additional 12.5% of the patients to a different risk-adapted therapy. The applied minimal screening-analysis-based diagnostic algorithm enabled improved and more precise diagnosis and clinical stratification in 37.2 % of AML patients from our study group.
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    A Case Report of Aggressive Adult Neuroblastoma Mimicking Acute Leukemia with Fulminant Course and Fatal Outcome
    (American Society of Hematology, 2008-11-16)
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    Ivanovski, Martin
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    <jats:title>Abstract</jats:title> <jats:p>Neuroblastoma is an embryonic neoplasm of the sympathetic nervous system derived from the primitive neural crest cells. It is the second most common extra cranial malignant tumor of childhood and the most common solid tumor of infancy, comprising 8 to 10 percents of pediatric cancers. Forty percent of patients who present with clinical symptoms at diagnosis are under 1 year of age, and less than 5% with clinical symptoms are over the age of 10 years. The tumor very rarely occurs in adult patient (defined as 20 years of age and older) and usually has an indolent course with poor survival. Up until June 2008, no more than 65 neuroblastomas in adults had been reported in the literature. Majority of the reports describe an indolent and longer course of the disease among adults with different biological characteristics when compared to children, but ultimately poor outcome regardless of the initial stage of the disease. Here, we report a case of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome. The patient, a previously healthy 38 years old Caucasian male, presented at our department with a 4 months history of hip pain, headaches, malaise, weakness, persistent diarrhea, poor appetite and weight loss. On admission he was febrile, prostrated, pale, fixed in bed. His abdomen was distended with present bowel movements. The liver and spleen were 3 cm and 5 cm below the costal margins respectively. No abdominal mass was palpable. Neurological examination showed right Horner’s syndrome, reduction of the superficial sensitivity on the Th1 and Th2 level and loss of the tendon-muscle reflexes of the lower limbs. He had paraplegia, indicating possible spinal cord compression. The complete blood counts revealed pancytopenia and presence of 11 % peculiar circulating blastoid cells. The LDH was 3552U/l. Under suspicion of acute leukemia bone marrow aspirate and biopsy was performed. Immunophenotyping of the bone marrow mononuclear cells showed presence of around 50% CD45negative, CD56 and CD9 positive cells, indicating a possible involvement of the bone marrow with neuroblastoma. A routine second opinion from a reference pathologist was also interpreted as neuroblastoma and confirmed with positive immunohistochemical staining for NSE, chromogranin, synaptophysin and negative for LCA. A work-up for neuroblastoma was done and investigations confirmed disseminated stage 4 neuroblastoma. In spite of the appropriate treatment with intensive chemotherapy regimen, the patient failed to improve and died of progressive disease. Our case report illustrate the usefulness of including CD56 marker in flow-cytometry acute leukemia assays, especially in cases when CD45 expression is absent, as initial screening tool for recognizing cases of neroblastoma which simulate acute leukemia.</jats:p>