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e19520 Background: The purpose of this study was to compare morphological and immunophenotypic characteristics of the tumor population of B-lymphocytes with varying restrictions of immunoglobulin light chains in patients with chronic lymphocytic leukemia (CLL). Methods: We examined 30 patients with CLL (median age 64.9±8.6 years). All patients underwent CBC+DIFF blood tests (Sysmex XE 2100, Japan), morphological examinations (BioVision; Micros, Austria), and immunophenotyping (IPT) by multicolor flow cytometry (Navios 10/3, Beckman Coulter, USA) of the bone marrow and venous blood. According to the IPT results, the patients were divided into: group 1 - 22 patients (73.3%) with tumor cells expressing kappa immunoglobulin light chains, and group 2 - 8 patients (26.7%) with lambda immunoglobulin light chains. Statistical processing of results was performed in the STATISTICA 13.0 program. Results: Morphological tests revealed differences between tumor populations of B lymphocytes. In group 1, the tumor population was represented by small cells of the same type with scanty, often unvisible cytoplasm and nuclei with a lumpy chromatin structure, without distinct nucleoli. In group 2, the sizes of cells varied from small to large, with abundant cytoplasm, round or folded nuclei, smoothed chromatin structure and 1-2 nucleoli. Prolymphocytes were observed among tumor cells (8.1±1.7% of WBC). IPT also revealed differences in tumor clones: morphological uniformity of tumor cells in group 1 was observed in the distribution of tumor cells reflected in low parameters of light scattering on the diagram: location to the left along the FSC axis - from 200 to 400 units and below along the SSC axis - from 10 to 160 units. In group 2, the lymphoid zone was heterogeneous and stretched on the plot: location to the right along the FSC axis - from 200 to 1000 units and higher along the SSC axis - from 10 to 400 units, closer to the monocyte zone, which indicated morphological polymorphism of tumor cells. The expression of CD45 also differed: in group 1, the expression was higher and tumor B lymphocytes were higher by fluorescence intensity on a dot plot on the CD45 / SSC scale in the second half of the third decade and in the fourth decade - to the right compared with group 2, where aberrant B lymphocytes were in the third decade and more to the left. The CD45 expression allowed defining differentiation of the tumor clone: the population in group 1 was represented by mature cells, and in group 2 by less mature and/or intermediate forms. There were no significant differences in the expression of other markers. The revealed differences were typical of both the peripheral blood and bone marrow. Conclusions: The study established morphological and immunophenotypic differences between tumor clones of B lymphocytes expressing either kappa or lambda immunoglobulin light chains in patients with CLL.

e19554 Background: The purpose of this study was to assess NT-proBNP as a marker of renal dysfunction in patients with diffuse large B-cell lymphoma receiving immune polychemotherapy. Methods: The study involved 24 patients aged 23-69 years (median 57 years) with a primary diagnosis of diffuse large B-cell lymphoma (DLBCL). The renal status was assessed by the blood serum levels of creatinine, urea, NT-proBNP (Vitros 5600, USA), sodium (Cobas b221, Switzerland) with the calculation of the glomerular filtration rate (GFR) according to the CKD-EPI formula, as well as urine levels of albumin (Cobas Integra 400 plus, Switzerland). The tests were conducted before and 48 hours after induction immune polychemotherapy (R-CHOP). Statistical evaluation of results was made using the Statistica 13.0 program. Results: The patients were divided into 2 groups depending on the GFR levels before the start of therapy: group 1 (n = 16) - GFR 108.04±13.9 mL/min/1.73 m2 (normal levels); group 2 (n = 8) - GFR 59.57±12.04 mL/min/1.73m2 (reduced levels). The studied parameters in group 1 were within the reference values before treatment: NT-proBNP 109.38±13.6 pg/mL, creatinine 72.67±7.96 μmol/L, urea 5.39±0.99 mmol/L, albumin in urine 4.34±0.51 mg/L. After 48 hours, a moderate increase in NT-proBNP up to 207.5±48.2 pg/mL (p > 0.05) was observed, without significant changes in other parameters. In group 2, a pronounced increase in NT-proBNP was observed initially: 694±206.47 pg/mL, which was 5.6 times higher than the upper limit of the reference interval (p < 0.001) and 6.4 times higher than the levels in group 1 (p < 0.001), together with a significant increase in urine levels of albumin - 43.93±12.03 mg/L. Creatinine (80.67±4.35 μmol/L) and urea (6.4±1.41 mmol/L) remained within the reference range. After 48 hours, NT-proBNP increased by 3.8 times, reaching 2675±602.4 pg/mL (p < 0.001), which was accompanied by an increase in urine albumin - 57.8±8.86 mg/L and serum creatinine – 102.2±5.37 μmol/L in comparison with the initial levels. The levels of urea remained unchanged (6.6±0.43 mmol/L). The sodium levels did not differ significantly between the groups and was 141.65±2.24 mmol/L in group 1 and 140.85±3.4 mmol/L in group 2 and did not change over time. According to the results, patients with an initially decreased GFR demonstrated an increase in the levels of NT-proBNP and albumin in the urine even before the start of polychemotherapy. Conclusions: NT-proBNP can be considered an early marker of renal dysfunction in patients with diffuse large B-cell lymphoma.

e20086 Background: The purpose of the study was to analyze changes in the erythron peripheral component during chemotherapy for malignant lymphomas in patients infected with parvovirus B19 (B19V). Methods: The study included 34 patients with lymphomas (48.7±4.3 years). B19V infection was determined by the presence of IgM/IgG antibodies to B19V in blood serum and DNA in blood plasma and bone marrow before chemotherapy (CT). Parameters of the erythron peripheral component - RBC, HGB, MCW, MCH, MCHC, RDW, PLT, RET (#), IRF, LFR, MFR, HFR (%), and myelogram were evaluated before and after CT (Sysmex XE 2100, Japan). Results: 82.5% of patients had IgG to B19V, including IgM in 11.8%. B19V DNA was detected in 23.4% of patients: in the bone marrow and blood in 11.7%, only in the bone marrow in 11.7%. The range of viral load in the bone marrow was 1435-79573 IU/ml, in the blood 2-349 IU/ml. RBC in all patients before CT was within the reference range, with a tendency to decrease in the group with B19V: 4.01±0.06×1012/L with B19V and 4.57±0.08×1012/L without B19V. Levels of HGB before CT were respectively 112±1.26 g/L and 116±1.26 g/L, decreasing after CT by 1.5 and 1.3 times (p < 0.05) depending on the viral load. MCV, MCH and MCHC varied: 78.6 – 84.8 fl, 24.9 – 28.0 pg and 314–330 g/L in the group with B19V, and 89.7–91.3 fl, 29.5–29.8 pg and 324–337 g/L, respectively, in the group without B19V, which indicates the development of hypochromic microcytic anemia. RET levels before CT in the group with B19V were 38.3±3.44×109/L, after CT – 10.6±2.7×109/L, being lower than in the group without B19V by 1.8 and 3.8 times (p < 0.001), respectively. IRF, MFR and HFR in patients with B19V before CT were 10.6±2.23%, 9.5±1.54% and 1.1±0.022%, being lower than in non-infected patients by 1.6, 1.3 and 3.6 times, respectively. After CT, the downward trend in the proportion of young fractions continued. The noted changes in the erythron peripheral unit indicated inhibition of erythropoiesis, more pronounced in patients with B19V, and were consistent with the myelogram data. Conclusions: The development of anemia without the expected increase in RET, and in particular immature forms - IRF, MFR, HFR - in patients with lymphomas and B19V infection indicates inhibition of erythropoiesis. Early manifestation of these changes allows for timely treatment correction.

e13510 Background: The high rates of mortality from venous thromboembolism (VTE) in neurooncological patients determine the relevance of the topic. The risk of VTE in patients with glioma reaches 36% during the treatment period, 16.1% during the first 6 months and increases by 3 times after tumor biopsy. The aim of this study was to evaluate the efficacy and safety of VTE treatment with fondaparinux after surgical interventions for brain tumors. Methods: The study included 32 cancer patients aged from 27 to 76 years (mean 56.5 years) in the acute period of VTE, the first month after craniotomy. Creatinine clearance below 30 ml/min, active bleeding, thrombocytopenia below 50x109/l were exclusion criteria. Glioma was diagnosed in 15 patients (46.9%), metastasis - 9 (28.1%), and meningioma - 8 patients (25%). Radical interventions were performed in 12 (37.5%) cases, palliative - 20 (62.5%). In 81.2% of cases (26 patients) deep vein thrombosis of lower extremities (DVT) was detected, 3 patients (9.4%) had combination with pulmonary embolism. VTE developed in the postoperative period with radiotherapy in 9 cases (32%), dexamethasone - 13 (40.6%). Surgical treatment of DVT was performed in 8 patients (thrombectomy, plication of the femoral vein). Segmental deep vein thrombosis of the lower leg was detected in 14 (43.8%) cases. Results: The efficiency of anticoagulant therapy was assessed by a decrease of thrombinemia markers (fibrinogen, SFMC and D-dimer). After a week of anticoagulant therapy, a significant reduction in the level of D-dimer was observed. However, the decline in fibrinogen and SFMC was statistically insignificant. VTE therapy was performed with fondaparinux in a therapeutic dose from 10 days to 1 month, followed by a transition to oral anticoagulants. There was no hospital mortality. Hematuria developed in one case (3.1%), and was managed conservatively. There were no hemorrhagic complications in the operative intervention zone. Two patients (6.25%) had a recurrence of VTE during the period of radiation therapy. Conclusions: An integrated approach to the treatment of VTE in patients undergoing craniotomy provides a low incidence of recurrent VTE and major bleeding.

e14506Background: The purpose of the study was to assess changes in biochemical markers of cardiotoxicity in anthracycline chemotherapy for breast cancer. Methods: The study included 30 pts (32-72 ...

e14505Background: We monitored some biochemical parameters to assess hepatotoxicity of anthracycline chemotherapy in patients with breast cancer. Methods: The study included 30 patients (32-72 year...

e17505Background: The purpose of the study was to determine the VEGF-A expression in patients with cervical cancer to assess its prognostic value. Methods: The study included 82 patients (23-70 yea...

e24327Background: The purpose of the study was to analyze the phenotypic profile of erythrocytes in Rhesus and Kell systems in patients with malignant and benign tumors. Methods: Phenotyping of ery...

e14508Background: We monitored the level of methotrexate and some laboratory parameters in patients with osteosarcoma to evaluate the toxicity of high-dosage EURAMOS chemotherapy. Methods: The stud...

e17019 Background: The purpose of the study was to analyze hormonal disorders in tissues of histologically unchanged ovaries of patients with cervical cancer infected with HPV/Chlamydia trachomatis. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4), steroid-binding globulin (SBG) and prolactin (PRL) by the ELISA in intact ovaries of 25 patients aged 53.4±3.2 years with cervical cancer T1b-2aN0M0. HPV presence was determined by Е7 protein expression, Chlamydia trachomatis (Ch. tr.) – by IgG and IgА to Ch. tr. and antigen/DNA by ELISA and Real-time PCR. Tissues of intact ovaries obtained during hysterectomy from 22 non-infected women of similar age with endometrial cancer T1N0M0 were used as the control. Results: The data demonstrated a sharp decrease in E2 level by 9.3 times and increase in E1 by 2.3 times in intact ovaries of cervical cancer patients infected with HPV and Ch. tr., compared with the values in controls. Changes were noted in the balance between some estrogen fractions: E1 percentage increased by 5 times, E3 – by 2.4 times and E2 percentage decreased by 4 times. Androgenic status in intact ovaries in cervical cancer was characterized with increased levels of T (by 5.1 times) and fT (by 1.6 times). We noted an increase in SBG concentration by more than 3 times in response to the release of androgens registered in ovarian tissue, as well as significant (by 4.4 times) increase in PRL and decrease in P4 by 1.5 times compared with non-infected tissues. Estrogens to P4 ratio in co-infected patients reduced by 1.6 times, while the PRL to P4 ratio increased by 6.4 times, mainly due to disorders in hormone-producing ovarian function. Conclusions: The development of malignant process in the cervix in a combined HPV and Chlamydia trachomatis infection is accompanied by disorders of the endocrine status in tissues of intact ovaries and shows the undeniable role of consequences of HPV/Chlamydia trachomatis coinfection in this process.

e22007 Background: The purpose of the study was to analyze phenotypic characteristics of red blood cells by the AVBO, Rh and Kell systems in children with cancer. Methods: ABO and Rh blood groups were determined and erythrocyte antigens (D, С, с, Сw, Е, е, К, k) were typed (AutoVue Innova, USA) in blood samples of 114 children with solid tumors. Results: ABO blood groups distribution was as follows: A(II) > O(I) > B(III) > AB(IV) with A(II) prevalence. Rh(D)-positive phenotype was observed in 82 (71.9%) patients of 114: 47 (57.3%) boys and 35 (42.6%) girls. 32 (28.1%) patients of 114 were Rh(D)-negative: 15 (46.8%) boys and 17 (53.1%) girls. Only 8 (7%) children were Kell-positive, which was similar to the antigen prevalence in European population. 4 erythrocyte phenotypes were the most frequent in Rh(D)-positive patients: СсDееK− (34.1%), ССDееK− (22.0%), ccDEeK− (13.4%) and СсDЕеK− (11.0%). I.e., more than a half of children with oncopathologies (56.1%) had Kell-negative phenotypes, СсDееK− and ССDееK−. 86.4% of Rh(D)-positive patients had homozygous combinations of Rhesus antigens causing transfusion reactions - СС, сc, ЕЕ and ее. 18 (22.0%) of Rh(D)-positive patients were homozygous for the C antigen and 64 (78.0%), i.e. every third patient, had the c antigen. Children with the C antigen may be sensitized to the c antigen through blood transfusion with subsequent development of hemolytic complications. The K (Cellano) antigen was found in all children, and 93% of them had kk phenotype and 7% - Kk. The Сw (Willis) antigen was revealed only in 5 (6.0%) Rh(D)-positive patients with rare phenotypes - CwCceeK-, CwccEeK-, CwCcEEK-, CwCcEeK-. Matching a donor for patients with one of these phenotypes could pose a problem. Conclusions: Studying phenotypic characteristics of red blood cells is necessary for providing a successful blood transfusion, especially in children Kell-positive for the K antigen, in children homozygous for the C antigen with ССDееК- phenotype and in children with the Сw antigen and СwСсееК-, СwссЕеК-, СwСсЕЕК- and СwСсЕеК- phenotypes.

e19511 Background: Our purpose was to analyze levels and types of paraprotein in polychemotherapy combined with selective plasma exchange in patients with multiple myeloma. Methods: Blood levels of paraprotein (PP) were studied by capillary electrophoresis (Helena Bioscience V8), and content of plasma cells was determined in the bone marrow of 16 patients (main group) with multiple myeloma (MM) during polychemotherapy (PCT) plus selective plasma exchange (SPE). 14 patients receiving standard PCT were the controls. Results: MM patients in both groups were characterized with the presence of PP in the blood serum with the M-peak in the gamma-globulin zone. Only heavy IgG chains were found, bound to lambda (λ) light chains in 48% and to cappa (κ) light chains in 57.15%. The initial PP level in MM-IgGλ was 91.01±0.79 g/L and was 2.4 times higher than in MM-IgGκ (38.3±0.34 g/L). Significant differences in were found in PP reduction rate and intensity depending on the treatment. PP in the main group reduced by 42.4% after course1, by 41.4% after course 2, by 52.2% after course 3 and by 24% after course 4; in the control group – by 17.2%, 19.3%, 27.9% and 47.3%, respectively. PP levels decreased by 87.4% and 74.6% by the end of the treatment, respectively. The data were confirmed by a decrease in plasma cell content in the bone marrow of patients: up to 1.2% in the main group and 6.2% in the controls. Response to treatment in the main group was registered at the early stages of therapy, and at the late stages in the control group. Treatment effect was associated with the type of secreted PP. In MM-IgGκ, PP levels in the main group decreased by 59.7% after course 1, by 40.6% more after course 2 and by 51.9% after course 3; in MM-IgGλ – by 25.1%, 42.1% and 52.5%, respectively. Treatment effect was noted earlier and PP reduction was more intensive in MM-IgGκ than in MM-IgGλ. PP levels decreased by the end of the treatment by 85.4% in MM-IgGκ and by 73% in MM-IgGλ. Similar changes were observed in the control group. Conclusions: Increased rates and intensiveness of paraprotein reduction reflect effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma. Patients with MM-IgGκ are more sensitive to the therapy.

e17020 Background: The role of Chlamydia trachomatis (Ch. tr.) in development of cervical neoplasia is widely discussed. However, molecular mechanisms of Ch. tr. contribution to carcinogenesis are poorly studied. The purpose of the study was to analyze degrees of DNA damage in blood leucocytes in patients with cervical cancer with Ch. tr. infection and in non-infected patients and healthy women. Methods: DNA damage was assessed by the comet assay, the alkaline single-cell gel electrophoresis (20 min, 300 mA, 20 V, 2 V/cm, 4°C) allowing detection of DNA base modifications leading to alkali-labile sites. The preparations were stained with ethidium bromide solution and microscoped (Axio Imager M2, Zeiss) at the excitation wavelength 520 nm and emission wavelength 640 nm. 200 cells were analyzed in each preparation. Percentage of DNAs in the comet tail (T%DNA) was used as an indicator of DNA damage. DNA damage was assessed in 14 patients with cervical cancer and in 13 healthy women. The data were analyzed using Exsel and Statistika 6.0 programs and Mann-Whitney U test and Student's t-test. Results: Mean T%DNA in 8 cervical cancer patients non-infected with Ch. tr. was 4.35±0.63, being significantly (р=0.012580) higher (by 53.7%) than in women without oncopathology (2.83±0.20). The value in infected patients was 10.44±0.11 which was significantly higher than in non-infected patients (by 2.4 times, р=0.000056) and in healthy women (by 3.7 times, р=0.000000). Thus, presence of Ch. tr. was associated with more than 2 times increase in DNA damage in cervical cancer patients. The results are consistent with previously reported data of cell culture studies according to which chlamydia causes histone modification and DNA double strand breaks [Chumduri C. et al., 2013]. Conclusions: The results confirm the role of chlamydia infection in DNA damage in blood cells in cervical cancer patients which promotes malignant development in organs of the female reproductive system.

e17579 Background: Our purpose was to evaluate changes in blood parameters in patients with laryngeal squamous cell carcinoma (LSCC) during polychemotherapy (PCT) with cetuximab. Methods: Levels of white blood cells (WBC), immature granulocytes (IG) and neutrophils (Ne), as well as levels of C-reactive protein (CRP), lactate dehydrogenase (LDH) and creatinine were studied in the blood of 20 patients with stage I-III LSCC before therapy with cetuximab/cisplatin+5-fluorouracil and on days 2, 9 and 16 of the therapy. The control group (21 patients) received similar PCT without cetuximab. Treatment was assessed using the RECIST criteria. Results: Partial response was observed in 16 (80%) patients of the main group and in 5 (23.8%) controls, stabilization - 4 (20%) and 12 (57.4%), respectively, progression – in 4 (19%) patients of the control group. Patients of the main group with treatment effect showed WBC increase by 2 times after every cetuximab injection (days 2, 9, 16) compared with the initial levels due to Ne and IG increase by 2.7 and 4 times, respectively. WBC and IG levels measured on days 2, 9 and 16 were 13.40±2.86×109/L, 13.52±1.88×109/L, 12.25±2.08×109/L and 0.044±0.021×109/L, 0.056±0.015×109/L, 0.060±0.008×109/L, respectively (p < 0.001). A transient increase in the indexes was replaced by their decrease to the initial values, with the values similar to the reference ones by the end of the treatment. At the same time, we observed decrease in CRP and creatinine levels up to the reference levels (7.69±3.28 mg/L and 74.75±6.54 umol/L, respectively); LDH did not increase. Stabilization was characterized by unchanged WBC levels, positive dynamics of IG and slow decline of CRP level exceeding the reference one (10.0 mg/L) by the treatment end. Reduction of WBC and increase in IG and CRP levels were noted in the controls regardless of the PCT results which could be explained by severity of intoxication syndrome, partially due to the disease and partially due to PCT toxicity. Conclusions: A dual transient increase in WBC and IG levels, reduction of CRP and creatinine during the treatment and unchanged LDH indicate minimization of myelotoxic and general toxic effects of PCT in combination with cetuximab.

e19510 Background: The purpose of the study was to analyze changes in reticulocytic indices and their role in assessing the effectiveness of erythropoiesis in patients with multiple myeloma. Methods: Thestudy included 10 patients with primary multiple myeloma (MM) and 16 patients with recurrent MM, stage II-III. Parameters of the peripheral blood were studied: Hb, RBC, MCV, MCH, RBC-He (red cell hemoglobin content), RET (number and percentage), IRF (immature reticulocyte fraction), high (HFR), median (MFR) and low (LFR) fluorescence reticulocytes, RET-He (reticulocyte hemoglobin content), RPI (reticulocyte production index). Results: Anemia was found in21 (80.8%) patients before treatment: grade I in 30.8%, II in 46.1%, III in 3.8%; normocytic hypochromic anemia – 6, normocytic normochromic – 15. Anemia detection rate in primary MM was 60.0%, recurrent – 93.7%. RET levels in grade I-II anemia were close to the norm, but IRF was increased due to MFR increase by 3.7 times and HFR – by 4.7 times. Grade III anemia: RET number decreased by 1.6 times due to IRF reduction by 2 times, in particular MFR and HFR fractions. As a result, RET-He was decreased to varying degrees in all cases. Patients with complete or partial remission showed no significant changes in erythrocyte parameters, but had RET level increased by 2.5 times, IRF – by 9 times due to MFR increase by 6.5 times and HFR by 30.8 times, RPI - by 2.0 times. The data showed the effectiveness of erythropoiesis during anticancer therapy. We did not observe signs of increasing anemia syndrome in patients with stabilization or patients resistant to treatment, as well as in patients with initial grade III anemia. Hb, RBC, RET and RPI were unchanged, but the ratio of fractions changed: the number of mature ones - LFR increased by 1.4 times and young ones - HFR decreased by 2.5 times, RBC-He were increased and RET-He doubled compared to the levels before treatment, which indicated the activation of processes of erythrokaryocyte hemoglobinization. Conclusions: RET, IRF, RET-He and RPI indices adequately reflect the process of recovery of erythropoiesis and its effectiveness in real time which is extremely important in tumor therapy monitoring.

e17018 Background: The purpose of the study was to analyze the effect of HPV/Chlamydia trachomatis co-infection on the hormonal status of tumor and visually unchanged cervical tissues in cervical cancer patients. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4) and prolactin (PRL) by the ELISA in tumors and visually unchanged cervical tissues of 49 patients with cervical cancer T1b-2aN0M0 with endophytic (25 patients) and exophytic (24 patients) patterns of tumor growth. 13 patients with endophytic tumors and 12 patients with exophytic ones were infected with HPV and Сhlamydia trachomatis (Ch.tr.). HPV infection was determined by Е7 protein expression, Ch.tr. – by IgG and IgА and antigen/DNA in ELISA and PCR. Intact cervical tissues obtained during hysterectomy from 22 non-infected women with endometrial cancer were used as the control. Results: Tumor tissues of the cervix without infection demonstrated increased levels of all sex steroids: estrogens by 3 times, androgens by 3.1 times and progestins by 1.8 times. Co-infected tissues were characterized by the sex-steroid imbalance. We observed reduced coefficients of estrogens to T and fT by 1.6 and 6 times, respectively, compared to intact tissues (most significant in a tumor with endophytic growth pattern) and an increase in the estrogens to P4 ratio by 1.5 times – only in endophytic growth pattern. Androgenic status in co-infected tumor tissues increased by 1.7 in endophytic and by 3.1 times in exophytic growth pattern. PRL level was increased only in co-infected tumors (by 2.5 times). Unchanged co-infected tissues, unlike non-infected samples, showed E2 increase by 2.6 times in exophytic and by 1.5 times in endophytic growth pattern, T increase by 1.6 times only in endophytic tumors and P4 decrease by 1.5 times and PRL increase by 1.8 times regardless the tumor growth pattern. Conclusions: Hormonal profile of both tumor and unchanged cervical tissues was dependent on HPV/Ch. tr. co-infection and tumor growth patterns. The changes could result from HPV and Ch. tr. interaction triggering malignant processes.