B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are considered as laboratory markers of inflammation. They can be potentially useful in predicting the course of multiple neoplasms including selected hematological cancers. The aim of the study was to assess the value of NLR and PLR in predicting the effects of therapy and prognosis in multiple myeloma patients treated with thalidomide-based regimen. The study group consisted of 100 patients treated with the first line CTD (cyclophosphamide, thalidomide, and dexamethasone) chemotherapy. The NLR and PLR were calculated before treatment. High NLR was observed in patients with higher stage of the disease, with poor performance status, hypercalcemia, and high CRP. High PLR was associated with low BMI and high CRP. In patients with high NLR, significantly shorter PFS was observed (17 vs. 26 months, p = 0.0405). In addition, high values of NLR and PLR were associated with significantly shorter OS (38 vs. 79 months, p = 0.0010; 40 vs. 78 months, p = 0.0058). Summarizing, NLR and PLR have a significant independent prognostic value for multiple myeloma patients. Furthermore, the NLR can be a predictive marker for the outcome of thalidomide-based chemotherapy.

The recently discovered JAK2 V617F point mutation, found in 50-60% of ET patients, has been reported to be associated with a higher risk of thrombotic events. In this study, we explored if JAK2 V617F mutation, or coexisting thrombophilic and hemostatic risk factors, contributed to these complications. We examined 32 patients with ET, and looked for pathogenetic JAK2 V617F mutation and prothrombotic genes mutations: factor V Leiden, prothrombin and MTHFR. We also evaluated plasma levels of fibrinogen, factors VIII and XII, AT, protein C, protein S and serum level of homocysteine. Urokinase concentration was assessed in patients' plasma as well as platelet lysates. There was no difference in the number of thrombotic complications between ET patients with and without JAK2 mutation. However, we found a number of thrombophilic and hemostatic risk factors that could contribute to thrombotic complications in ET patients. (Folia Histochemica et

The pathogenesis of Buerger' disease (thrombangiitis obliterans; TAO) remains unknown, although a strong association with tobacco use has been established. Blood coagulation and fibrinolytic factors as well as selected clinical chemistry parameters have been evaluated in 37 patients with Buerger's disease. Median levels of prothrombotic factors were higher in patients with TAO than in healthy control: annexin V (P < 0.0003), factor VII (P < 0.0001), factor VIII (P < 0.0000001), factor XI (P < 0.000003), homocysteine (P < 0.014) and fibrinogen (P = 0.00007). Patients with Buerger's disease also showed higher median plasma levels of urokinase type plasminogen activator (uPA) (P < 0.000004), its receptor (uPAR) (P < 0.0008) and uPA complex with plasminogen activator inhibitor 1 (uPA-PAI-1) P < 0.000006). In contrast, plasma concentrations of apolipoprotein A and folic acid were lower in patients with TAO than in control (P < 0.004 and P < 0.0006; respectively). Higher plasminogen (P < 0.05) and cholesterol (P < 0.003), as well as lower folic acid (P < .0.05) levels were noted in the smokers group than in nonsmoking patients. We found higher plasminogen (P < 0.05), factor VII (P < 0.05), total lipids (P < 0.003), cholesterol (P < 0.05) and triglycerides (P < 0.002) levels in patients requiring surgical treatment for limb-threatening ischaemia than the patients treated only conservatively. These findings suggest an important role of haemostatic risk factors in the pathogenesis of Buerger's disease, with special regard to hyperhomocysteinemia that might be aggravated by low serum folic acid level. In patients with aggressive clinical course, disturbances in serum lipids were more pronounced. Further studies are warranted to establish whether diet supplementation of folic acid as well as normalization of lipids balance might influence the clinical course of TAO.

The paper presents a study on the changes in cognitive functioning in patients undergoing chemotherapy with diagnosed multiple myeloma (MM). The aim of the study was to answer the following two main research questions: Does the treatment stage differentiate the functioning of cognitive processes in patients with diagnosed MM and to what extent? Is it possible to treat biological factors (TNF-α, IL-6, IL-10, and BDNF) as predictors of patients’ cognitive functioning? The patients were examined twice, before the treatment and after 4–6 cycles of chemotherapy. Selected neuropsychological research methods as well as experimental and clinical trials were employed to diagnose the patients’ general cognitive state, attention, memory, and executive functions. The level of biological factors was assessed with the ELISA test. The results show that the patients’ cognitive functioning was worse before the treatment than during the cytostatic therapy. It was also possible to predict the cognitive state of patients suffering from multiple myeloma based on a selected biological parameter (neurotrophin BDNF).

Buerger’s disease or thrombangiitis obliterans (TAO) is non artherosclerotic vascular disease that most commonly affects the small and medium-sized peripheral arteries and veins. Although a strong association with tobacco use has been established, the cause of the disease remains unknown. Possible pathogenic factors include autoimmune phenomena, haemostatic factors abnormalities and hyperhomocystynemia, however their role still remains controversial. In this study we investigated the role of blood coagulation and fibrinolytic factors abnormalities in the development of TAO. We assessed plasma activity of factor VII (FVII) factor VIII (FVIII), factor IX (FIX), plasminogen (PLG), urokinase type plasminogen activator (uPA) and its receptor (uPAR), uPA complex with plasminogen activator inhibitor 1 (uPA-PAI-1), anexin V, apolipoprotein A (ApoA), homocysteine, folic acid and serum lipids profile. Blood samples were collected from 37 patients with TAO (8 female and 29 male) with median age 39.5 years (ranging from 20 to 50 years). In patients with Buerger’s disease there were significantly higher levels of prothrombotic factors as compared to healthy control: anexin V (8.27±6.28 ng/ml vs 2.93±2.06 ng/ml, p=0.0003), FIX (109.72±30.05% vs 78.54±12.28%, p=0.000003), FVII (123.28±30.10% vs 104.36±43.38%, p=0.0001), FVIII (119.85±44.39% vs 60.19±20.77%, p=0.0000001), homocysteine (11.53±2.88 μmol/l vs 9.86±2.20 μmol/l, p=0.01) and fibrinogen (5.06±1.94mg/dL vs 3.31±1.03mg/dL, p=0.00007). Mean uPA, uPAR and uPA/PAI-1 complex plasma levels were also higher in patients with Buerger’s disease than in healthy control: 1067.07±264.97pg/mL vs 979.01±170.93pg/mL, p=0.0008; 1798.22±438.43pg/mL vs 1348.20±194.95pg/mL, p=0.000004; 303.60±288.16pg/mL vs 110.17±166.71pg/mL, p=0.000006, respectively. In contrast, plasma concentrations of ApoA and folic acid were significantly lower in patients with TAO compared to healthy control: 135.30±18.77pg/dL vs 156.46±19.97pg/dL, p=0.004 and 4.82±2.35mg/dL vs 6.84±2.70mg/dL, p=0.0006; res. Moreover there was a significant correlation between prothrombotic factors plasma levels: FIX and plasminogen (R=0.44) as well as between FVII and uPA-PAI complex (R=0.52). We found significant differences concerning studied parameters between smoking and non-smoking patients with TAO: i.e. significantly higher level of PLG (120.66±14.33pg/mL vs 108.07±17.97pg/mL, p=0.03), total cholesterol (198.36±43.95mg/dL vs 178.64±44.93mg/dL, p=0.001) and triglycerides (161.36±117.47mg/dL vs 103.50±63.20mg/dL, p=0.04), as well as lower plasma levels of folic acid (4.43±2.31mg/dL vs 5.59±2.39mg/dL, p=0.02) in smokers group. Coffee use correlated only with increased homocysteine plasma level (12.31±2.70 vs 9.96±2.68, p=0.04). In 72.2% of TAO patients, surgery was required due to aggressive disease. In this group, we found higher level of plasminogen (119.78±15.34pg/mL vs 105.12±16.35pg/mL, p= 0.04), FVII (128.50±28.90% vs 109.70±30.70%, p=0.03), total lipids (692.49±186,33mg/dL vs 514.00±96.30mg/dL, p=0,002), cholesterol 201.73±42.63mg/dL vs 162.00±38.46mg/dL, p=0.02) and triglycerides (163.62±110.70mg/dL vs 74.50±27.09mg/dL, p=0.001) as compared to the patients treated only conservatively. Our results indicate an important role of hemostatic risk factors in pathogenesis of Buerger’s disease with special regard to increased plasma concentration of homocysteine that was proved to cause lesions of blood vessels endothelium. Decreased serum level of folic acid that was found in TAO patients may contribute to hyperhomocysteinemia. Patients with aggressive clinical course of TAO, requiring surgical treatment had more disturbances in serum lipids. These findings suggest that diet supplementation of folic acid as well as normalization of lipids balance might influence clinical course of TAO.

Introductionκ and λ serum free light chains (sFLCs) are produced during physiological lymphopoesis by plasmocytes and B lymphocytes in a constant ratio related to heavy chains. The measurement of sFLC plays an important role in the diagnosis and monitoring of patients with multiple myeloma (MM). The first reports suggested that sFLC disturbances might have prognostic value also in patients with chronic lymphocytic leukemia (CLL). Aim of the study: The aim of the study was to evaluate the relationship between sFLC concentration and recognized prognostic factors and clinical course of CLL. Materials and methods: The sFLC concentration was measured using a latex-enhanced immunoassay in 59 patients with newly diagnosed CLL. The relationship between sFLC concentration and time to start of the treatment (TFT), the response rate to therapy (ORR) and overall survival (OS) was assessed.ResultsA significant correlation was found between sFLC κ concentration and the clinical stage of leukemia according to Rai classification, β-2 microglobulin concentration, LDH activity, CD38 expression, as well as between sFLC λlevel and β-2 microglobulin concentration and platelet count (PLT ). There was also a correlation between the values of summated κ and λ and the clinical stage of disease according to Rai classification, β-2 microglobulin concentration, CD38 expression, white blood cells count (WBC), lymphocyte count (ALC) and hemoglobin (Hgb) concentration. The κ/λ ratio (FCLR) values were significantly different in the CD38+ and CD38- population.SummarySimple and reproducible clonality index, which constitutes the sFLC concentration assessment, can be an attractive, potential prognostic marker in patients with CLL, however further studies are needed on a larger group of patients especially in relation to the predictive value of sFLC.

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