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    Milena Todorovic

    Conventional hematopoietic stem cell transplantation is a well-known treatment method for numerous acquired and congenital hematopoietic disorders, disorders of the immune system, as well as certain metabolic disorders. Stem cells (SCs)... more
    Conventional hematopoietic stem cell transplantation is a well-known treatment method for numerous acquired and congenital hematopoietic disorders, disorders of the immune system, as well as certain metabolic disorders. Stem cells (SCs) can be defined as cells capable of self-renewal with a high proliferative capacity and the potential to differentiate into functionally competent mature cells. Stem cells can be divided into embryonic SCs (ESCs) and tissue-specific or adult SCs - such as bone marrow (BM) stem cells, peripheral blood (PB) stem cells, and SCs derived from umbilical cord blood (UCB), as well as other non-hematopoietic or somatic SCs. SCs in adults are characteristically considered to be restricted in their regenerative and differentiative potential, while embryonic stem cells are 'true' totipotent/pluripotent cells, due to their ability to develop into endoderm, ectoderm, or mesoderm - all three embryonic tissue types in the human body. They are the most promisi...
    Stem cells (SC) are the unique and "key-cells" in the human body "working" as a source of producing a large number (proliferation) of mature (differentiation) cells inside different tissues ("cytopoiesis") -... more
    Stem cells (SC) are the unique and "key-cells" in the human body "working" as a source of producing a large number (proliferation) of mature (differentiation) cells inside different tissues ("cytopoiesis") - while at the same time maintaining the ability to "reproduce" themselves (self-renewal). These events are balanced by interactive signals from the extracellular matrix, as well as microenvironment provided by stromal cells. On the other hand, SC plasticity (so-called "inter-systemic plasticity") is the ability of the most "primitive" (immature) adult SCs to switch to novel identities. The phrase SC plasticity also involves phenotypic potential of these cells, broader than spectrum of phenotypes of differentiated cells in their original tissues. Recent increasing clinical use of cell-mediated therapeutic approaches has resulted in enlarged needs for both, higher quantity of SCs and improved operating procedures during ex...
    Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome
    Background/Aim. Stem cells (SCs) guarantee complete/longterm bone marrow (BM) repopulation after SC-transplants. The aim of the study was to evaluate absolute count of total SCs (determined by ISHAGE-sequential-gating protocol ? SCish)... more
    Background/Aim. Stem cells (SCs) guarantee complete/longterm bone marrow (BM) repopulation after SC-transplants. The aim of the study was to evaluate absolute count of total SCs (determined by ISHAGE-sequential-gating protocol ? SCish) and relative frequency of immature CD34+/CD90+ (CD90+SCish) subset in peripheral blood (PB) as predictive factors of mobilization and apheresis product (AP) quality. Methods. Mobilization included chemotherapy and granulocytegrowth- factor (G-CSF). Harvesting was performed by Spectra- Optia-IDL-system. The SCsish were determined as a constitutional part of CD34+ cells in the ?stem-cell-region? using FC- 500 flow-cytometer. In this study, the original ISHAGEsequential- gating protocol was modified by introduction of anti-CD90-PE monoclonal-antibody into the analysis of CD90 expression on SCish (CD90+SCish). The results were presented as a percentage of SCish per nucleated-cell count, absolute SCish count in ?L of the PB or the AP, percentage of the CD9...
    Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable... more
    Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6(+) protein expression into BCL-6(-) expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6(-) patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between ...
    Background/Aim. The use of peripheral blood as a source of hematopoietic stem cells (SCs) is progressively increasing and has nearly supplanted bone marrow transplantation. Interpatient variability in the degree and kinetics of SC... more
    Background/Aim. The use of peripheral blood as a source of hematopoietic stem cells (SCs) is progressively increasing and has nearly supplanted bone marrow transplantation. Interpatient variability in the degree and kinetics of SC mobilization into peripheral blood is an expected event after conventional chemotherapy-based treatment, followed by sequential administration of recombinant granulocyte-colony- stimulating factor (rHu-CSF). In this study, specific factors associated with the application of two different SC-harvesting approaches, including the use of large volume leukapheresis (LVL) vs. repetitive conventional apheresis (RCA), were analyzed. The basic goal of the study was to evaluate the influence of apheresis protocol (collection timing, processed blood volume and cell yield) upon the clinical outcome of transplantation. Methods. Results obtained by LVL (76 pts) and RCA (20 pts - control group) were compared. The SC mobilizing regimen used was cyclophosphamide (4-7 g/m2)...
    The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis has prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the... more
    The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis has prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the prognostic significance of ALC and AMC and to determine whether ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in DLBCL. We retrospectively analyzed the prognostic significance of ALC and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 DLBCL patients treated with R-CHOP. ROC analysis showed that optimal cut-off values of AMC and ALC/AMC ratio with the best sensitivity and specificity were 0.59×10(9)/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1×10(9)/L). Low ALC, high AMC, low ALC/AMC ratio and high ALC/AMC prognostic score were in significant association with lower rate of therapy response and survival. In contrast, these parameters were not in significant correlation with relapse rate. The patients with low ALC, "high" AMC, low ALC/AMC ratio and high ALC/AMC prognostic score at diagnosis had significantly shorter EFS and OS. In multivariate analysis all tested parameters (ALC, AMC, ALC/AMC prognostic score and ALC/AMC ratio) are independent risk factors along with "bulky" disease and IPI. All tested parameters (ALC, AMC, ALC/AMC score and ALC/AMC ratio) may be useful prognostic factors in DLBCL patients. ALC/AMC score has a slight advantage as it allows the classification of patients into three prognostic groups. Further studies are needed to determine which of these parameters has the highest predictive value.
    Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal B-cell tumors that generally follow an indolent course. The gastrointestinal tract is the most common site of MALT lymphoma, comprising 50% of all cases. The tissue lesions... more
    Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal B-cell tumors that generally follow an indolent course. The gastrointestinal tract is the most common site of MALT lymphoma, comprising 50% of all cases. The tissue lesions are often localized, have high therapeutic response rates with late relapses with a long overall survival (OS). The patients with non-gastric lesions may follow a different clinical course and many of them present with disseminated disease. This study reports a series of 51 patients with non-gastric MALT lymphoma. Twenty patients (39.2%) presented with disseminated disease, seven (13.7%) patients had two MALT mucosal sites involved and eight (15.7%) had involvement of three or more mucosal sites. At presentation, 17 (33.3%) patients had the lymph node and 12 (23.5%) the bone marrow involvement. Following various combinations of treatment, complete remission was achieved in 40 (81.6%), and partial remission in three of the 49 treated patients with no difference in response rates between different disease stages. Relapse occurred in 12/43 (27.9%) patients among whom eight (18.6%) recurred in the presenting organ system. Five patients (9.8%) died because of a rapid disease progression after a median follow-up of 56 months; two patients with primary lung lesions, 1 patient with secondary intestinal disease, and 2 patients suffered transformation to diffuse large B-cell lymphoma. No significant difference in survival was found between localized and disseminated disease (log rank 0.05, df = 1, P = 0.81). A patient age > or = 60 yr at diagnosis and presentation with the nodal disease were found to be statistically significant negative prognostic factors (P < 0.05). Median OS was not reached after 145 months of follow-up, with the estimated OS being 88% at 2 yr, and 78% at 5 yr.
    Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome
    In last several decades, we have seen great advance in all lymphoma treatment. The significant progress was made in treatment of many B-cell lymphomas with introduction of purine analogs like fludarabine, monoclonal antibodies like... more
    In last several decades, we have seen great advance in all lymphoma treatment. The significant progress was made in treatment of many B-cell lymphomas with introduction of purine analogs like fludarabine, monoclonal antibodies like rituximab, and high dose chemotherapy with autologous stem cell transplantation. That improved treatment of chronic lymphocytic leukemia, small lymphocytic, marginal zone, follicular or even diffuse large B-cell lymphoma. Unfortunately, this success was less prominent in entities like mantle cell NHL (MCL) and in T-cell NHL.
    The objective of this chapter is to provide a systematic overview of current knowledge regarding therapeutic apheresis—primarily therapeutic plateletapheresis (TP)—and to summarize evidence-based practical approaches related to... more
    The objective of this chapter is to provide a systematic overview of current knowledge regarding therapeutic apheresis—primarily therapeutic plateletapheresis (TP)—and to summarize evidence-based practical approaches related to cytapheresis treatment of “hyperthrombocytosis” or “extreme thrombocytosis” (ETC). Our results of platelet (Plt) quantitative/qualitative analyses and evaluation of efficacy of apheresis systems/devices—on the basis of Plt removal and in vivo Plt depletion—will be presented. Our preclinical researches confirmed that in Plt concentrates, the initial ratio of discoid shapes was 70%, spherical 20%, and less valuable (dendritic/balloonized) shapes 10%—with morphological score of platelets (MSP = 300–400). After storage, the ratio of discoid and spherical shapes was decreased, while the less valuable ones progressively increased (MSP = 200). Electron microscopy has shown discoid shapes with typical ultrastructural properties. Spherical shapes with reduced electron...
    Hematopoietic stem cells (SCs) are responsible for the production and replacement (proliferation) of an extensive quantity of functionally competent blood cells (differentiation) during the entire life, while simultaneously maintaining... more
    Hematopoietic stem cells (SCs) are responsible for the production and replacement (proliferation) of an extensive quantity of functionally competent blood cells (differentiation) during the entire life, while simultaneously maintaining the ability to reproduce themselves (self-renewal). A complex network of interactive substances and factors organize and protect the survival, maturation and multiplication of SCs. Hemobiological events in the bone marrow (BM) are synchronized and balanced by the extracellular matrix and microenvironment provided by stromal cells. These cells-including macrophages, fibroblasts, dendritic, endothelial and other cells-stimulate SCs by producing specific hematopoietic growth factors. Other cytokines secreted by stromal cells regulate the adhesion molecules positioned on SCs, allowing them to remain in the BM or migrate to an area where the respective cell type is needed. Thus, hematopoietic SCs could be defined as cells with high proliferative capacity a...
    Stem cells could be defined as cells capable for self-renewal with high proliferative capacity and extensive potential to differentiate into blood cells or some somatic cell types - ?plasticity? due to ?trans-differentiation? - such as... more
    Stem cells could be defined as cells capable for self-renewal with high proliferative capacity and extensive potential to differentiate into blood cells or some somatic cell types - ?plasticity? due to ?trans-differentiation? - such as osteocytes, chondrocytes, hepatocytes, myocytes, cardiomyocytes and even endothelial cells. Recent increasing clinical use of various cell-mediated therapeutic approaches has resulted in amplified needs for both stem cells and operating procedures to get a minimized cell damages during collection, purification and cryopreservation. The aim of cell harvesting procedures is to obtain the best stem cells yield, high purity and good viability/clonogenicity. The goal of optimized cryoinvestigation protocols is to minimize cell injuries during the freeze/thaw process (cryoinjury). Despite the fact that different stem cells collection protocols and cell freezing practice are already in routine use, a lot of questions related to the optimal blood stem cells h...
    Introduction. The most common causes of subocclusive disorders are the adhesion, Crohn's disease and small bowel neoplasms. Plasmablastic lymphoma (PBL) is an aggressive distinct subtype of diffuse large B-cell non-Hodgkin lymphoma... more
    Introduction. The most common causes of subocclusive disorders are the adhesion, Crohn's disease and small bowel neoplasms. Plasmablastic lymphoma (PBL) is an aggressive distinct subtype of diffuse large B-cell non-Hodgkin lymphoma initially reported in the oral cavity of the HIV infected individuals. Case report. We presented a male patient with PBL of the small intestine as a rare cause of intestinal subocclusion, without HIV infection and negative serology for hepatitis C, hepatitis B, and Epstein-Barr infection. A 73-year-old male was admitted to our Center due to the one-year history of abdominal pain, weigh loss, non-bloody diarrhea, night sweating and pruritus. The patient underwent the ileocolonoscopic examination with the accompanying biopsy specimens. The results, based on the histopathological and immunohistochemical pattern, confirmed a diagnosis of PBL. Following the chemotherapy treatment, our patient underwent the resection of ileum. The postoperative histopatholo...
    Background/Aim. Despite the introduction of new oral anticoagulants (dabigatran, rivoroxaban, apixaban), vitamin K antagonists (VKA), such as warfarin and acenocoumarol are still the most widely used oral anticoagulants for the treatment... more
    Background/Aim. Despite the introduction of new oral anticoagulants (dabigatran, rivoroxaban, apixaban), vitamin K antagonists (VKA), such as warfarin and acenocoumarol are still the most widely used oral anticoagulants for the treatment of non-valvular atrial fibrillation (NVAF). Time in therapeutic range (TTR) represents a measure of the quality of the anticoagulant effect of these drugs, and it is considered that the lower value of TTR is associated with the adverse effects of therapy. The study aim was to evaluate of the effectiveness of VKA therapy in patients with NVAF and to identify factors affecting the anticoagulation efficacy. Methods. A retrospective study was conducted on a population of 725 outpatients with NVAF, treated with VKA and followed in Blood Transfusion Institute of Nis from January to December 2017. Laboratory control of the INR was done from capillary blood of patients on Thrombotrack Solo (Axis Shield, Norway) and Thrombostat (Behnk Elektronik, Germany). Targeted therapeutic INR was between 2.0 and 3.0. For each patient we evaluated all available INR values to calculate the individual TTR according to the Rosendaal method. Results. The study included a total of 725 patients with NVAF which had 6105 INR measurements, what is 8.13±2.47 INR measurements per patient. The mean value of TTR and was 60.15±17.52%, but 49.72% of patients had a TTR less than 60%. Patients were at high risk of thrombosis in 6.15% of time (INR 4.5). The most significant independent factors affecting the quality of VKA therapy are gender, arterial hypertension, diabetes mellitus and the use of amiodarone and antiplatelet drugs (aspirin, clopidogrel). Conclusion. The TTR is undoubtedly useful indicator of the effectiveness of VKA treatment. The most important predictors of poorer efficacy of VKA therapy are arterial hypertension, diabetes mellitus, patints' gender and the use of amiodarone and antiplatelet (aspirin, clopidogrel) drugs. To improve the quality of VKA therapy, education of patient and better collaboration with them, as well as a successful teamwork with clinicians are also imperative.
    Background/Aim. Intravenous drug users (IDUs) are still a high risk-group for cross-reacting blood-borne infections, for vertical pathogen transmission as well as for potentially blood/plasma donation (especially as ?paid? donors). The... more
    Background/Aim. Intravenous drug users (IDUs) are still a high risk-group for cross-reacting blood-borne infections, for vertical pathogen transmission as well as for potentially blood/plasma donation (especially as ?paid? donors). The aim of our study was to establish the profile of opiate addict and prevalence of blood-borne pathogens ? Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV) among 99 patients on substitution therapy with methadone and buprenorphine from Sumadia District. Methods. The Treatment Demand Indicator (TDI) of Pompidou-questionnaire was used to assess the history of drug abuse and risk behavior. All blood samples were tested for HBV surface antigen (HBsAg), anti-HCV antibody (anti-HCV) and HIV antigen/antibody (HIVAg/ Ab) by Enzyme-Linked ImmunoSorbent Assay (ELISA) or Chemiluminescent Immuno-Assay (CIA). Investigations were also performed for HBV, HCV and HIV by molecular testing ? Polymerase Chain Reaction (PCR) method. R...
    Early detection of the platelet storage lesion is still a challenge in transfusion practice. Using flow cytometry, we evaluated the appearance of the storage lesion, based on the expression of platelet activation markers, in total... more
    Early detection of the platelet storage lesion is still a challenge in transfusion practice. Using flow cytometry, we evaluated the appearance of the storage lesion, based on the expression of platelet activation markers, in total platelets and platelet populations. Buffy-coat-derived platelet concentrates were stored under standard conditions for 5 days. The expression of activation antigens CD42b, CD36, CD62p and phosphatidylserine on total platelets and populations of small, medium-sized and large platelets was analysed by flow cytometry on storage days 1, 3 and 5. The activation/lesion on total platelets and each platelet population was detected on storage day 3, by the increased expression of CD36. On the same day, increased expression of CD42b and CD62p was detected, but only on large platelets. Small and medium-sized platelets had increased CD62p expression only on day 5. Externalisation of phosphatidylserine was not detected. Evaluation of the level of expression of various ...
    The syndrome of paraganglioma (PGL), somatostatinoma (SOM), and early childhood polycythemia in patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A) gene is described in only a few patients worldwide. The... more
    The syndrome of paraganglioma (PGL), somatostatinoma (SOM), and early childhood polycythemia in patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A) gene is described in only a few patients worldwide. The present study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings these experiences into perspective with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with secondary polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent, and metastatic in 100%, 100%, and 29% of all cases, and SOMs in 40%, 40%, and 60%, respectively. All PGLs were primarily norepinephrine producing. All patients had abnormal ophthalmologic findings...
    Background The influence of comorbidities in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has been modestly investigated. Different comorbidity scoring systems are available for cancer patients. Aims In order... more
    Background The influence of comorbidities in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has been modestly investigated. Different comorbidity scoring systems are available for cancer patients. Aims In order to evaluate the impact of comorbidities on the overall survival (OS) we have performed retrospective analyses of clinical records of the patients with DLBCL treated with R-CHOP, R-EPOCH and R-CVP protocol. The following comorbidity scores were used: Cumulative Illness Rating Scale (CIRS), Charlson Comorbidity Index (CCI), age adjusted CCI (aaCCI) and Hematopoietic-Cell-Transplantation Comorbidity Index (HCT-CI) Methods A total of 378 patients (195 female/183male) were included in the study. Median age was 58 years (range 18-80). Elderly population (70 years and older) represented 20.2% of analyzed group. According to the Ann Arbor classification, stage I, II, III and IV had 51patients (13.5%), 129 (34.1%), 72 (19%) and 129 (33.3%), respectively. Bulk...
    The aim of this study was to evaluate the prognostic significance of international prognostic index (IPI), mantle cell lymphoma IPI (MIPI), simplified MIPI (sMIPI), and MIPI biological (MIPIb), as well as their correlation with... more
    The aim of this study was to evaluate the prognostic significance of international prognostic index (IPI), mantle cell lymphoma IPI (MIPI), simplified MIPI (sMIPI), and MIPI biological (MIPIb), as well as their correlation with immunophenotype, clinical characteristics, and overall survival (OS), in a selected group of 54 patients with advanced-stage mantle cell lymphoma (MCL), treated uniformly with CHOP. Seventeen patients had IV clinical stage (CS), while other 37 had leukemic phase at presentation. Diffuse type of marrow infiltration was verified in 68.5% and nodular in remainder patients. Extranodal localization (25.9%) included bowel (20.4%), pleural effusion, sinus, and palpebral infiltration. All of analyzed patients expressed typical MCL immunophenotypic profile: CD19(+)CD20(+)CD22(+)CD5(+)Cyclin-D1(+)FMC7(+)CD79b(+)smIg(+)CD38(+/-)CD23(-)CD10(-). Median OS of the whole group was 23 months, without significant differences between IV CS and leukemic phase patients. Thirty-tw...
    Acquired haemophilia A is a rare autoimmune disorder caused by factor VIII (FVIII) inhibitors. Patients may present with catastrophic bleeding, despite having no prior history of bleeding disorders. Acquired haemophilia A is a rare... more
    Acquired haemophilia A is a rare autoimmune disorder caused by factor VIII (FVIII) inhibitors. Patients may present with catastrophic bleeding, despite having no prior history of bleeding disorders. Acquired haemophilia A is a rare complication of pregnancy, typically appearing in the postpartum period. The patients usually present with bleeding related to vaginal delivery or Caesarean section. Management includes control of haemorrhage and eradication of the FVIII inhibitor. Acquired haemophilia A was diagnosed in our patient after profuse vaginal bleeding related to vaginal delivery (FVIII level 2%; FVIII inhibitor titar 16 BJ). Red cell, fresh frozen plasma and cryoprecipitate transfusions, as well as vaginal packing were ineffective. The administration of recombinant activated factor VII (rFVIIa) (NovoSeven) proved effective in stopping the bleeding. To facilitate eradication of the inhibitor prednisone (30 mg orally/d) was added. After 3 weeks of treatment, the inhibitor FVIII ...
    Dear Sir, Toxic epidermal necrolysis (TEN) or Lyell’s syndrome is a life-threatening (up to 90% mortality rate), extensive cutaneous, drug-induced adverse event1. Similar skin damage/defects -but usually without a fatal outcome- are... more
    Dear Sir, Toxic epidermal necrolysis (TEN) or Lyell’s syndrome is a life-threatening (up to 90% mortality rate), extensive cutaneous, drug-induced adverse event1. Similar skin damage/defects -but usually without a fatal outcome- are observed following drug administration in Stevens-Johnson’s syndrome (SJS; milder form) and TEN/SJS (intermediate type). In these conditions the epidermis can be detached from the underlying structures (dermis) over the whole body surface. Mucous membranes may also be affected. The precise aetiopathogenesis of TEN is still unclear. Some toxic metabolites, inflammatory mediators or modifiers, as well as cytotoxic T lymphocytes, regulatory T cells and dermal dendrocytes could induce apoptosis or necrosis of epithelial cells1–3. The human leucocyte antigen (HLA) system also plays an important role in the pathogenesis of TEN, since some drugs may bind directly to the HLA-complex and create self-reactivity due to the drug-modified HLA-peptide repertoire. This event is mediated by cytotoxic T lymphocytes and/ or natural killer cells after their interaction with cells expressing the HLA-complex3. We report here the case of a 21-year old female with extensive erythema, necrosis, and exfoliating bullous detachment of the epidermis and mucous membranes (conjunctival, oral and genital; affected skin area=80%; Figure 1A and 1B). Initially, she had an influenza-like prodrome after taking ibuprofen to treat a headache and dysmenorrhea. She was admitted to the Clinic for Plastic Surgery of MMA (Belgrade, Serbia) and on presentation she was febrile (39.3 °C) with a characteristic positive Nikolsky’s sign. Laboratory analyses were as follows: haemoglobin, 121 g/L; white blood cell count, 6.77×109/L (neutrophils 80%, lymphocytes 25%, eosinophils 4%, monocytes 1%), platelet count, 466×109/L; elevated levels of C-reactive protein, aspartate aminotransferase and alanine aminotransferase (330 mg/L, 80 IU/L and 145 IU/L, respectively), and low concentrations of total proteins (50 g/L) and albumin (22 g/L). The results of coagulation studies and tests for viral infections were normal. Skin biopsy demonstrated prominent cell death with basal vacuolar changes and lymphocyte infiltrates, obscuring the dermo-epidermal junction (Figure 1C), which confirmed the clinical diagnosis of TEN. Figure 1 A) and B) Female patient with TEN: extensive erythema, necrosis, and critical muco-cutaneous lesions with intense exfoliation. C) Cell destruction with lymphocyte infiltrates and distraction of the dermo-epidermal junction. D) Therapeutic apheresis - ... The first-line treatment was immediate withdrawal of theculprit drug, elimination of the drug and its metabolites, and fluid resuscitation with crystalloid infusions (1 mL/kg of body weight per hour) via a central venous catheter, adjusted on the bases of the arterial blood pressure (>65 mmHg), central venous pressure (≤10 mmHg) and urine output (diuresis rate). The patient was isolated (using aseptic techniques and state) and local dermatological and ocular topical treatment were applied continuously. Nutrition was provided enterally via a nasogastric tube. In the early treatment of this patient, we performed our originally designed multimodal therapeutic apheresis -plasma exchange (PE) combined with leucapheresis- using COBE®-Spectra apheresis-sets (Terumo BCT, Lakewood, CO, USA) and a sterile connected multibag system. Multimodal therapeutic apheresis simultaneously provides rapid improvements in more than one blood abnormality and aids the patient’s recovery from a live-threatening emergency to a clinical condition with a potentially positive outcome4,5. The rationale for initial plasma exchange in this case was to eliminate/decrease the level of residual ibuprofen and its metabolites, critical cytokines (such as tumour necrosis factor-α, interferon-γ), and drug-induced inflammatory mediators (perforin, granzyme B released from cytotoxic T lymphocytes and granulysin secreted by cytotoxic T lymphocytes and natural killer cells) from the circulation (urgent plasma depuration). Plasma exchange was performed on three consecutive days by processing an average of 5900±952 mL of the patient’s whole blood. A total of 5.4-fold the plasma volume was exchanged and replaced by albumin in normal saline (Figure 1D). The basic goal of the leucapheresis-treatment was to reduce the circulating lymphocyte count in the patient’s blood to obtain an immunomodulatory effect. The patient’s subsequent systemic treatment included broad-spectrum antibiotics (chosen on the basis of the skin microbial findings), intravenous immunoglobulins (dose 1.0 g/kg of body weight per day for 3 consecutive days; infused over 6 hours) and corticosteroids (dose 0.5 mg/kg of body weight)1,2. This young female patient recovered completely after 1 month of intensive systemic and topical treatment. In conclusion, this multidisciplinary management -fluid resuscitation, urgent plasma depuration and…
    Background/Aim. Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established.... more
    Background/Aim. Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease - aGvHD) and delayed (chronic GvHD - cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS). Methods. We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML) - 39, acute lymphoblastic leukemia (ALL) - 47, chronic myeloid leukemia (CML) - 32, myelodysplastic syndrome (MDS) - 10, Hodgkin?s lymphoma ...
    Background/Aim. Introducing tyrosine kinase inhibitors (TKIs) has essentially changed curative approach, to be precise, clearly improved treatment efficacy for chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem... more
    Background/Aim. Introducing tyrosine kinase inhibitors (TKIs) has essentially changed curative approach, to be precise, clearly improved treatment efficacy for chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem cell transplant (SCT) in CML treatment - as a former "nearly monopolistic" therapeutic manner - is nowadays controversial. The objective of this retrospective study was to evaluate the results obtained in the treatment of CML patients, with a particular attempt to define parameters critical for clinical benefit and superior overall outcome following allogeneic SCT. Methods. A total of 32 CML patients (27 in chronic phase and 5 with advanced disease), with female/male ratio 11/21, aged from 9 to 54 (32 in average) years, underwent allogeneic SCTs (1993 to 2009). The initial treatment for 25 patients was interferon alpha (IFN-?) with or without ARA-C, and additional 7 patients with no response to imatinib mesylat (IM). The time from diagnosis...
    In engineering practice exergy can be used for technical and economic optimization of energy conversion processes. The problem of increasing energy consumption suggests that heating plants, i.e. hot water boilers, as energy suppliers for... more
    In engineering practice exergy can be used for technical and economic optimization of energy conversion processes. The problem of increasing energy consumption suggests that heating plants, i.e. hot water boilers, as energy suppliers for household heating should be subjected to exergy and energy analysis. Heating plants are typically designed to meet energy demands, without the distinguished difference between quality and quantity of the produced heat. In this paper, the energy and exergy analysis of a gas fired hot water boiler is conducted. Energy analysis gives only quantitative results, while exergy analysis provides an insight into the actually available useful energy with respect to the system environment. In this paper, a hot water boiler was decomposed into control volumes with respect to its functional components. Energy and exergy of the created physical model of the hot water boiler is performed and destruction of exergy and energy loss in each of the components is calcul...
    Based on the results of clinical trials, there is no global consensus on the optimal first-line therapy for patients with advanced Hodgkin lymphoma (HL) with both ABVD and BEACOPP currently being used. However, the results of clinical... more
    Based on the results of clinical trials, there is no global consensus on the optimal first-line therapy for patients with advanced Hodgkin lymphoma (HL) with both ABVD and BEACOPP currently being used. However, the results of clinical trials are usually better than those in daily practice. We thus describe here our experience on 314 advanced classical HL patients treated with ABVD at the Clinical Center of Serbia and associated centers between 1997 and 2008. The median follow-up for all patients was 91 months; the estimated 5-yr event-free survival was 62% and the 5-yr overall survival (OS) 76%. Multivariate Cox regression analysis revealed that patients with IPS ≥ 3 and extranodal disease involving more than one site have a poorer outcome. The data presented here show on overall improvement in outcome as compared to more previous data and illustrate the problems of treating advanced stage HL outside the setting of a clinical trial.
    Introduction. Special entities like solitary bone plasmocytoma (SBP) or extramedullary plasmacytoma (EMP) can be found in a less than 5% of patients with plasma cell disorders. EMP of the tongue represents very rare localization of the... more
    Introduction. Special entities like solitary bone plasmocytoma (SBP) or extramedullary plasmacytoma (EMP) can be found in a less than 5% of patients with plasma cell disorders. EMP of the tongue represents very rare localization of the head and neck plasmacytoma. Case report. We report a case of 78-years-old woman who developed EMP of the tongue base detected by the magnetic resonance imaging (MRI) of the head and neck region. Immunohistochemical profile of the tumor tissue biopsy (CD38, IgG, kappa positivity) indicated diagnosis of EMP. The diagnosis was established with additional staging which confirmed the absence of other manifestation of the disease. The patient was treated with 40 Gy of radiotherapy in 20 doses resulting in the achievement of the complete remission of the disease. This case was discussed with the reference to the literature. Conclusion. EMP of the tongue base is a very rare entity of plasma cell dyscrasias. Appropriate irradiation results in the achievement o...
    Primary testicular lymphoma (PTL) is a rare and highly aggressive extranodal... more
    Primary testicular lymphoma (PTL) is a rare and highly aggressive extranodal non-Hodgkin's lymphoma. We evaluated the clinical and histopathological features and outcomes of 10 PTL patients treated in the period of 2003-2013 with multimodal therapy (rituximab, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), intrathecal prophylaxis, irradiation of the contralateral testis) following orchiectomy. Complete remission was achieved in 8 patients after first-line therapy while 2 patients had disease progression. The median follow-up duration was 30 months (range 6-110 months). Relapse occurred in 3 patients. 1 patient relapsed in the contralateral testis, while the other 2 patients relapsed to the skin and the central nervous system (CNS), respectively. The time to relapse was 2, 8, and 9 months. Patients with disease progression and relapse received ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) as salvage treatment, except for 1 patient who was treated with palliative radiotherapy. After second-line therapy, only 1 patient had a short partial remission of 2 months. The median overall survival was 48 months, and the mean progression-free survival was 36 months (the median was not reached). We evaluated 10 patients with PTL treated with rituximab plus CHOP, prophylactic intrathecal chemotherapy, and prophylactic irradiation of the contralateral testis, resulting in good outcome and low incidence of relapse in the contralateral testis; however, the benefit of intrathecal chemotherapy is not yet confirmed.
    Background/Aim. Bacterial contamination of blood components, primarily platelet concentrates (PCs), has been identified as one of the most frequent infectious complications in transfusion practice. PC units have a high risk for bacterial... more
    Background/Aim. Bacterial contamination of blood components, primarily platelet concentrates (PCs), has been identified as one of the most frequent infectious complications in transfusion practice. PC units have a high risk for bacterial growth/multiplication due to their storage at ambient temperature (20 ? 2?C). Consequences of blood contamination could be effectively prevented or reduced by pathogen inactivation systems. The aim of this study was to determine the Mirasol pathogen reduction technology (PRT) system efficacy in PCs using an artificial bacteria-contamination model. Methods. According to the ABO blood groups, PC units (n = 216) were pooled into 54 pools (PC-Ps). PC-Ps were divided into three equal groups, with 18 units in each, designed for an artificial bacteria-contamination. Briefly, PC-Ps were contaminated by Staphylococcus epidermidis, Staphylococcus aureus or Escherichia coli in concentrations 102 to 107 colony forming units (CFU) per unit. Afterward, PC-Ps were...

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