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Background: Plerixafor is a bicyclam molecule with the ability to reversibly bind to receptor CXCR-4 thus leading to an increased release of stem cells (SC) into the circulation. This study aims to evaluate the efficacy of G-CSF plus plerixafor versus G-CSF alone mobilizing regimens on the basis of CD34+ cell yield and engraftment kinetics following hematopoietic SC transplants. Methods: The study incorporated 173 patients with plasma cell neoplasms (PCN), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), undergoing mobilization and following autologous SC-transplant. For patients with mobilization failure and those predicted to be at risk of harvesting inadequate CD34+ yields (poor-responders), plerixafor was administered. Data was collected and compared in relation to the harvesting protocols used, cell quantification, cell-engraftment potential and overall clinical outcome. Results: A total of 101 patients received plerixafor (58.4 %) and the median CD34+increase was 312 %. Chemotherapy-mobilized PCN-patients required less plerixafor administration (p = 0.01), no difference was observed in lymphoma groups (p = 0.46). The median CD34+cell yield was 7.8 × 106/kg bm. Patients requiring plerixafor achieved lower, but still comparable cell yields. Total cell dose infused was in correlation with engraftment kinetics. Patients requiring plerixafor had delayed platelet engraftment (p = 0.029). Conclusions: Adequately selected plerixafor administration reduces ''mobilization-related-failure'' rate and assure a high-level cell dose for SC transplants, with superior ''therapeutic-potential'' and safety profile. The mobilization strategy that incorporates ''just-in-time'' plerixafor administration, also leads to a reduction of hospitalization days and healthcare resource utilization. For definitive conclusions, further controlled/larger clinical trials concerning correlation of CD34+ cell count/yield, with hematopoietic reconstitution are required.

Abstract Background Although cytomegalovirus (CMV) is not considered tumorigenic, there is evidence for its oncomodulatory effects and association with hematological neoplasms. Conversely, a number of experimental and clinical studies suggest its putative anti-tumour effect. We investigated the potential connection between chronic CMV infection in patients with B-lymphocyte (B-cell) malignancies in a retrospective single-center study and extracted relevant data on CMV prevalences and the incidences of B-cell cancers the world over. Methods In the clinical single-center study, prevalence of chronic CMV infection was compared between patients with B-cell leukemia/lymphoma and the healthy controls. Also, global data on CMV seroprevalences and the corresponding country-specific incidences of B- lineage neoplasms worldwide were investigated for potential correlations. Results Significantly higher CMV seropositivity was observed in control subjects than in patients with B-cell malignancies (p = 0.035). Moreover, an unexpected seroepidemiological evidence of highly significant inverse relationship between country-specific CMV prevalence and the annual incidence of B-cell neoplasms was noted across the populations worldwide (ρ = −0.625, p 70 countries disclosed a link between CMV and B-cell neoplasms. Our evidence hints at an antagonistic effect of chronic CMV infection against B-lymphoproliferation.

Up to 60% of patients with aggressive B-cell lymphoma who receive chimeric antigen receptor (CAR) T-cell therapy experience treatment failure and subsequently have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a potentially curative approach for patients in this situation. Induction of a deep response prior to alloHSCT is crucial for long-term outcomes, but the optimal bridging strategy following relapse after CAR T-cell therapy has not yet been established. Polatuzumab vedotin, an antibody drug conjugate targeting CD79b, is a novel treatment option for use in combination with rituximab and bendamustine (Pola-BR) in relapsed or refractory disease. Patients: We report two heavily pretreated patients with primary refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) respectively who relapsed after therapy with CAR T-cells with both nodal and extranodal manifestations of the disease. After application of three courses of Pola-BR both patients achieved a complete metabolic remission. Both patients underwent alloHSCT from a human leukocyte antigen (HLA)-mismatched donor following conditioning with busulfan and fludarabine and are disease free 362 days and 195 days after alloHSCT respectively. We conclude that Pola-BR can be an effective bridging therapy before alloHSCT of patients relapsing after CAR T-cell therapy. Further studies will be necessary to define the depth and durability of remission of this salvage regimen before alloHSCT.

In the last twenty years, many companies have realized that the demands of the global market, including more demanding and receptive customers, have set new standards for production flexibility. Gradual reduction of mass production, characteristic of a large number of companies, has opened space for the introduction of a new system which focuses exclusively on the customer. The customer-oriented system was created with the idea that process optimization would lead to the production of a relatively cheap product, delivered on time and with the best possible quality. Such a system is achieved by applying the Lean Six Sigma concept. The aim of this paper is to identify all of the defects that occur as losses and complicate the process of production in order to achieve the Lean Six Sigma level in the Shinwon Company. The original data from the Shinwon company were identified, collected and analyzed, using the methods and tools of the Lean Six Sigma concept (Process Mapping, 5S audit, Pareto diagram, Ishikawa diagram, Seven basic wastes and SPC analysis), in order to present the effectiveness of the quality management system and to evaluate the possibility of its continuous improvement.

This paper presents a methodology for applying the Lean Six Sigma method on the educational process. After defining defects that have negative influence on the final quality evaluation of higher education and how these defects can be remedied, the Pareto analysis is done, and that is used for establishing a vital minority of the exams that are critical for examination of faculty. The next step is the Statistical Process Control (SPC) analysis that is performed on the exams that are classified as vital minority in Pareto analysis. Ishikawa diagram shows a relation between considered consequence (small number of passed exams) and all factors that influence this consequence. Based on the results of implementation of the Lean Six Sigma method in the educational process and implementation of all suggested improvements, the comparative overview of Pareto analysis is given for 2009/2010 and 2012/2013 academic year at the Faculty of Mechanical Engineering, University of Niš.

The most commonly used central units in the district heating system are most certainly hot water boilers. Experience in exploitation as well as their former development have given rise to new demands and possibilities of using hot water boilers for achieving a more efficient utilization of fuel. Yet, the current trend is not only for an efficient operation in terms of energy efficiency of primary fuel, but it also comprises many strict requirements when it comes to a cost-effective, reliable and safe operation. A mathematical - empirical model of the hot water boiler during the start-up process is presented in this paper. The dynamic behavior of the object will be discussed in the start-up regime because it represents one of the most critical transient regimes during the operation.

Abstract Background Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. Objectives This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. Methods We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. Results Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077–2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4–4.96), international normalized ratio (OR 0.21, 95% CI: 0.05–0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53–0.94), and intensive therapy (OR 2.05, 95% CI: 1.07–3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. Conclusion We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis.

Introduction: Cytomegalovirus (CMV) infection is a major clinical issue after allogeneic hematopoietic stem cell transplantation (HSCT). The CMV envelope glycoproteins are key in viral pathogenesis; the glycoprotein B (gB) encoded by the UL55 gene might be an important determinant of viral virulence and disease severity marker in patients treated with allogeneic HSCT. Our aim was to investigate the molecular diversity of CMV gB and inquire into the associations between UL55 gene variations and clinical manifestations in adult patients treated with allogeneic HSCT. Results: The most prevalent genotypes were gB1 and gB4 (11/27, 40.7%). Patients with genotype gB1 infection had earlier platelet engraftment (p < 0.033) and less frequent minimal/measurable residual disease post HSCT than those without this genotype. Patients with gB4 glycoprotein infection had a significantly lower CD4+/CD8+ ratio at D90 (p < 0.026). Interestingly, patients with gB5 glycoprotein infection had shorter overall survival from base condition diagnosis (p < 0.042), as well as shorter overall survival after HSCT (p < 0.036). Acute GvHD was noted more frequently in those with mixed-genotype infection (p = 0.047). Material and Methods: The study included fifty-nine adult patients treated with allogeneic HSCT. Peripheral venous blood was sampled typically per week, with detection of CMV performed by quantitative real-time PCR. Multiplex nested PCR was used to determine specific gB genotypes, which were then statistically compared vis-à-vis specific clinical variables. Conclusions: Our study points to variations in the viral UL55 locus imparting both beneficial (earlier platelet engraftment, less frequent MRD post HSCT) and adverse effects (shorter overall survival, more frequent acute GvHD, less frequent 100% chimerism at day 90) to the transplanted host. Comprehensive molecular investigations are necessary to validate this apparent duality, as the potential benefits of CMV could perhaps be utilized for the benefit of the patient in the future.

The oncogenicity of the human cytomegalovirus (CMV) is currently being widely debated. Most recently, mounting clinical evidence suggests an anti-cancer effect via CMV-induced T cell-mediated tumor destruction. However, the data were mostly obtained from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. Our study examined the correlation between country-specific CMV seroprevalence (across 73 countries) and the age-standardized incidence rate (of 34 invasive tumors). The populations studied were stratified according to decadal age periods as the immunologic effects of CMV seropositivity may depend upon age at initial infection. The International Agency for Research on Cancer of the World Health Organization (IARC WHO) database was used. The multivariate linear regression analysis revealed a worldwide inverse correlation between CMV seroprevalence and the incidences of 62.8% tumors. Notably, this inverse link persists for all cancers combined (Spearman’s ρ = −0.732, p < 0.001; β = −0.482, p < 0.001, adjusted R2 = 0.737). An antithetical and significant correlation was also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this oncopreventive phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, additionally supporting the idea of a common underlying mechanism—CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, in-depth investigation of host–virus interactions is still warranted.

Interprofessional cooperation and teamwork among health professionals in the health care system are crucial for improving patient satisfaction and quality of health services. The aim of the research is to examine the satisfaction of patients with interpersonal cooperation and health services provided at the level of primary and secondary health care. The research was done as a cross-sectional study and was conducted at the Niksic General Hospital and two health centers in Podgorica. The sample consisted of 154 respondents, both sexes. The research used a questionnaire for health care users designed for the purposes of this research. The questionnaire consists of a general and a specific part. Descriptive statistics measures and x2 test were used for statistical data processing. The results of the research show that there is a statistically significant correlation between gender and patient satisfaction with services χ² (2, N = 154) = 104.117, p = 0.000, as well as between age and patient satisfaction with services χ² (6, N = 154) = 139.294, p = 0.000. Understanding interpersonal cooperation is important for improving the efficiency of health care, its organization and customer satisfaction.

Background/Aim. Autologous stem cell transplants (ASCTs) improve the rate of overall survival (OS) in patients with hematological malignancies such as multiple myeloma (MM) after induction chemotherapy, aggressive non-Hodgkin's lymphomas (NHL), and relapsed, chemotherapy- sensitive Hodgkin's lymphoma (HL). The study aim was to evaluate influence of applied CD34+ cell quantity on clinical outcome, as well as early post-transplant and overall survival (OS) of HL and MM patients following ASCT. Methods. This study included a total of 210 patients (90 HL/120 MM) who underwent ASCT. Stem cell (SC) mobilization was accomplished by granulocyte-colony stimulating factor (G-CSF) 10-16 µg/kg body mass (bm) following chemotherapy. For proven poor mobilizers, mobilization with G-CSF (16 µg/kgbm) and Plerixafor (24 or 48 mg) was performed. To our best knowledge, it was the first usage of the Plerixafor in our country in the ASCT-setting. Harvesting was initiated merely at "cut-off-value" of CD34+ cells = 20 × 106/L in peripheral blood with "target-dose" of CD34+ cells = 5 × 106/kgbm in harvest. The CD34+ cell count and viability was determined using flow cytometry. Results. The majority of HL patients (76.7%) were infused with > 5.0 × 106/kgbm CD34+ cells, while 68.3% of MM patients were treated by approximately 4.0-5.4 × 106/kgbm CD34+ dose, respectively. Beneficial response (complete/partial remission) was achieved in 83.3% (HL) and 94.2% (MM) patients. Among parameters that influenced survival of HL patients with positive response to the therapy, multivariate analysis (pre-ASCT performance status, CD34+ cell quantity applied, rapid hematopoietic, i.e. lymphocyte and platelet recovery) indicated that higher CD34+ cell dose used, along with pre-ASCT performance status correlated with superior event-free survival (EFS) and OS following ASCT. In MM patients, multivariate analysis (renal impairment, infused CD34+ cell quantity, early platelet recovery) indicated that the number of CD34+ cells infused was the most important parameter that influenced both EFS and OS after ASCT. Conclusion. Data obtained in this study undoubtedly confirmed that CD34+ cell dose applied is an independent factor that may contribute to superior clinical outcome and OS of HL and MM patients following ASCT. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplant with high-dose chemotherapy is considered to be an effective treatment strategy for outcome improvement in lymphoma patients, especially those with refractory and relapsed disease. Despite the feasibility and efficacy of autologous stem cell transplant, patients with lymphoma still face the risk for relapse, mostly patients who have adverse prognostic features. Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant is recognized as the most effective strategy for relapsed or refractory Hodgkin lymphoma or aggressive non-Hodgkin lymphoma improving their response rate. First line therapy is ABVD (Hodgkin lymphoma patients), R-CHOP or R-CHOP-like regimens while salvage regimens such as DHAP, ESHAP, ICE represent the standard of care for relapsed/refractory lymphoma patients. Before autologous stem cell transplant, standard condition regimens are BEAM or CBM [ABSTRACT FROM AUTHOR]

Hepatitis-associated aplastic anemia occurs in up to 10% of all aplastic anemia cases. Syngeneic bone marrow transplantation is rare in patients with severe aplastic anemia and usually requires pre-transplant conditioning to provide engraftment. We report on a 29-year-old male patient with hepatitis-associated severe aplastic anemia who had a series of severe infectious conditions before transplantation, including tracheal inflammation. Life-threatening bleeding, which developed after bronchoscopy, was successfully treated with activated recombinant factor VII and platelet transfusions. Syngeneic peripheral blood stem cell transplantation using immunosuppressive treatment with antithymocyte globulin and cyclosporin A without high-dose pre-transplant conditioning was performed, followed by complete hematologic and hepatic recovery.

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.

Introduction. Limited efficacy of standard chemotherapy initiated the introduction of high-dose therapy followed by autologous stem cell transplantation in the treatment of patients with multiple myeloma. The aim of the study was to analyse results of treatment with high-dose therapy followed by autologous stem cell transplantation in 110 newly diagnosed multiple myeloma patients during the period May 2015 - January 2016. Material and Methods. Patient group consisted of 51 female and 59 male patients with average age of 57 years. Most of the patients were diagnosed with IgG myeloma (58.2%) and clinical stage III (74.5%, Salmon&Durie). Renal impairment initially existed in 26 patients. By 2008, patients were treated with 4-6 cycles of induction chemotherapy according to the protocol VAD (33 patients, 30%); and afterward according to the CTD protocol (72 patients, 65.5%). Mobilization of the stem cell was performed according to the protocol CAD followed by granulocyte colony-stimulating factor 5-10 pg/kg body weight/day starting on day 9, until the apheresis around day 14 of mobilization (± 1-2 days). Within 4-8 weeks after mobilization, HDT with Melphalan 200 mg/m2 accompanied with autologous stem cell transplantation was performed. Results. Applied induction treatment resulted in the achievement of at least partial remission in 80% patients. The average number of CD34+ in the product of apheresis was 8.1x106/kgBW, while during HDT with autologous stem cell transplantation, median was 4x106/kg body weight CD34+ cells. Average recovery was registered around +15 days after autologous stem cell transplantation, characterized by a minimal number of febrile days (median 2 days, range 0-10 days). In 95% patients, partial remission was recorded +100 days after autologous stem cell transplantation with average duration of 45 months, and achievement of complete remission in 29% pts with median overall survival of 100 months. This treatment approach resulted in overall survival longer than 45 months in more than 90% patients. The factors found to affect the duration of remission and overall survival are: ISS score >2. Conclusion. High-dose therapy followed by autologous stem cell transplantation is an efficient and safe treatment approach to multiple myeloma patients. Along with biological characteristics of the disease, complete remission achievement after such treatment is of essential significance for the course and outcome of multiple myeloma patients. [ABSTRACT FROM AUTHOR]