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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19554-e19554
    Abstract: 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 m 2 (normal levels); group 2 (n = 8) - GFR 59.57±12.04 mL/min/1.73m 2 (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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e20027-e20027
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15009-e15009
    Abstract: e15009 Background: Multiple myeloma (MM) is a B-cell malignancy resulting from the abnormal proliferation of neoplastic plasma cells that produce monoclonal immunoglobulin (Ig). The high variability of the course of this disease, its genetic clonal heterogeneity, is due to chromosomal deletions, chromosomal hyperploidy involving an odd number of chromosomes, as well as genetic aberrations, such as rearrangement of the Ig heavy chain gene loci. Since the available biomarkers do not take into account this feature of MM, there is a need to develop more advanced biomarkers that will more accurately predict the course of the disease and response to treatment. Methods: The collection of MM samples included biological samples obtained from patients over 18 years of age with a diagnosis of MM, who received treatment in the National Medical Research Center of Oncology since 2019. Only patients who signed an informed consent for the use of their biomaterial for scientific purposes were included in the project. The material was collected according to the developed algorithm of clinical information and biological material collection, sample preparation, quality control and storage in the cryostorage of the National Medical Research Centre for Oncology of the Ministry of Health of Russia (Rostov-on-Don). Results: As of December 23, 2021, collection consists of 387 samples of whole blood, serum, plasma and mononuclear cells obtained from 42 MM patients of both sexes, whose average age was 59.7 ± 1.49 (±SD) years. Each patient was assigned a unique identification number. Freezing of the obtained samples occurred in accordance with the low-temperature storage protocol. Registration, accounting and certification of the material were carried out in a specialized database for recording and storing information about biological samples. Conclusions: The identification of MM biomarkers is important for increasing the sensitivity of molecular monitoring, which makes it possible to stratify patients into risk groups for early relapses and treatment resistance development. Thanks to the accumulated experience, the Biobank of the National Medical Research Centre for Oncology of the Ministry of Health of Russia serves as a valuable resource for providing research in the development of new predictive molecular markers.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19520-e19520
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19559-e19559
    Abstract: e19559 Background: About 30-40% of patients with diffuse large B-cell lymphoma (DLBCL) do not respond to treatment, they subsequently relapse or remain refractory, so the search for predictive factors for the treatment effectiveness is relevant. TGF-β is a pleiotropic regulator of many pathophysiological processes, including carcinogenesis and immune responses, and its signals are initiated via its binding with proteins, including TGF-β receptor type 1 and type 2 (TGFBR2). The purpose of this study was to analyze the TGFβ1 and TGFBR2 blood levels and their ratio in patients with DLBCL depending on the treatment efficacy. Methods: The study included 63 patients (32 men and 31 women aged 23-88 years, median age 55.6 years) diagnosed with DLBCL. Blood levels of TGFβ1 and TGFBR2 were determined by ELISA before and after treatment. Stage I DLBCL was registered in 6 (9.5%) patients, stage II in 25 (39.7%), stage III in 5 (7.9%), stage IV in 27 (42.9%). All patients received standard treatment with R-CHOP, R-CHOEP, R-EPOCH. Direct results of the treatment were assessed by Cheson’s criteria. By their response to the therapy, patients were divided into 3 groups: group 1 (25.4%) – relapsed disease, group 2 (25.4%) – refractory disease, and group 3 (49.2%) – remission. A group of healthy donors included 20 men and women. All patients gave their informed consent to the study. Results: Blood levels of TGF-β1 in all patients before the treatment were higher than in donors by 2.1 times, and after the treatment by 2.4, 1.9 and 1.9 times, respectively, in groups 1, 2 and 3. The values between the groups did not differ significantly. Levels of TGFBR2, on the contrary, were lower in patients before treatment than in donors by 3 times, and after treatment by 3.5 in group 1, by 4 times in group 2, and similar to the norm in group 3. The TGFβ1/TGFBR2 ratios in patients before treatment were 6.1 times higher than the norm. After treatment, the ratio in patients of groups 1 and 2 were 8.6 and 7.2 times higher than in healthy donors. The ratio in patients of group 3 was 2.3 times higher than in healthy donors, and the value differed significantly from the values in groups 1 (3.8 times lower) and 2 (3.2 times lower). Conclusions: Monitoring the TGFβ1/TGFBR2 ratio in DLBCL patients before and during the treatment will allow promptly determination of adverse outcomes and changing the treatment regimen.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e19572-e19572
    Abstract: e19572 Background: The development of lymphomas is accompanied by disorders in the structural and functional organization of the immune system leading to immune deficiency. Such patients are at greater risk of severe SARS-CoV infection. Our purpose was to assess the parameters of cellular immunity in patients with lymphomas with a history of multi-course chemotherapy, therapy with anti-CD20+ antibodies and PCR-confirmed COVID19. Methods: The study included 12 adult patients with lymphoproliferative diseases (non-Hodgkin's large B-cell lymphomas (NHL) - 7, Hodgkin's lymphomas (HL) - 5) with a history of PCR-confirmed COVID-19. All patients underwent 4 to 6 chemotherapy cycles. The relative numbers of the main populations of leukocytes, T- and B-lymphocytes, as well as subpopulations of T-lymphocytes, were assessed in the whole blood collected in K2EDTA anticoagulant using the BD FACSCanto II flow cytometer with a panel of antibodies according to the manufacturer's instructions (Becton Dickinson, USA). Results: Patients with HL showed a number of changes in the parameters of cellular immunity. The content of total lymphocytes and monocytes was reduced in comparison with patients with NHL by 34% and 56%, respectively: 14.3 (11; 17) vs. 21.7 (15.2; 32), and 6.0 (4.8; 7.1) vs. 13.5 (12.9; 13.7), respectively. An increase in granulocytes by 30% was revealed in patients with HL. No differences were found in the content of both general and main populations (CD3+, CD3+CD4+, CD3+CD8+, central and effector memory cells). However, the content of naive CD3+CD4+ and CD3+CD8+ lymphocytes in patients with HL increased by 43% and 62%, respectively. While the number of CD3+CD4-CD8- lymphocytes was 47% lower, the number of CD3+CD4+CD8+, on the contrary, exceeded the values in patients with NHL by 4.6 times. Patients with HL also showed a tendency towards a decrease in the number of NK and NKT-lymphocytes. Conclusions: The increased levels of naive lymphocytes and both populations of memory cells and a sharp increase in double-negative T-lymphocytes and B-lymphocytes in patients with HL could indicate certain characteristics of the disease course affected by COVID-19. The data require additional research and can be used to assess the condition of patients and to predict the therapy efficacy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19564-e19564
    Abstract: e19564 Background: Patients with non-Hodgkin's lymphomas (NHL) develop abnormalities in the structural and functional organization of the immune system leading to immune deficiency. Chemotherapy (CT) in patients after SARS-CoV infection is associated with a more severe disease course affecting the treatment results. The cytokine-producing activity (CPA) of blood cells is poorly studied, while it determines the effectiveness of antitumor and anti-infective functions of the immune system. The purpose of this study was to evaluate CPA of peripheral blood mononuclear cells in patients receiving treatment for NHL after COVID-19. Methods: The study included 8 patients with large B-cell NHL with PCR-confirmed COVID-19 infection in past medical history. All patients received from 3 to 4 chemotherapy cycles. K2EDTA blood samples obtained before and after 3-4 CT cycles were divided into 2 parts after dilution with a sterile nutrient medium solution: part 1, to assess spontaneous CPA; part 2, with addition of a sterile mitogen (phytohemagglutinin 4 μg, concanavalin A 4 μg, and lipopolysaccharide 2 μg) to assess stimulated CPA. The samples were incubated for 24 hours at 37 0 C, and the levels of IL-1β, IL-6, IL-8, IL-10, IL-18, IL-4, IL-2, TNF- α, INF-ɣ, INF-α were determined in the obtained plasma. The stimulation coefficient (SC) was calculated as the ratio of stimulated CPA to spontaneous CPA. Results: 3-4 CT cycles in patients after COVID-19 was accompanied by an elevation of spontaneous CPA of the blood cells IL-6, INF-ɣ, TNF-α, IL-8, compared to the initial levels, by 678%, 127%, 64% and 57%, respectively. The ability of cells to spontaneous production of IL-10 and INF-α decreased by 30% and 100%. The mitogen-induced CPA of mononuclear cells in relation to IL-10, IL-6, IL-2, IL-1β and INF-α increased by 300%, 130%, 92%, 52% and 52%, respectively. Stimulated CPA in relation to INF-ɣ decreased by 21% compared to initial levels. As a result of the revealed CPA changes, SC in NHL patients after COVID-19 receiving CT increased, compared to the initial levels, by 465%, 92% and 48% respectively for IL-10, IL-2, IL-1β, as well as the appearing ability to INF-α production. SC for IL-6, INF-ɣ, TNF-α, and IL-8 decreased by 70%, 66%, 33% and 27% respectively. Conclusions: Certain features of spontaneous and mitogen-activated CPA of blood mononuclear cells were revealed in NHL patients after COVID-19, indicating a change in the functional activity of immune cells which could affect the development of the disease and the effectiveness of the therapy. The data obtained require additional studies and can be used to assess the condition of patients, as well as to predict the therapy efficacy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19560-e19560
    Abstract: e19560 Background: Diffuse large B-cell lymphoma (DLBCL) represents about 30-40% of all cases of non-Hodgkin lymphoma. The addition of rituximab to standard chemotherapy significantly improves survival, yet 30% of advanced-stage patients relapse. The International Prognostic Index (IPI) is used to evaluate the prognosis, but it cannot always accurately predict the outcome of therapy. The neutrophil-to-lymphocyte ratio (NLR) has recently been recognized as a prognostic factor in various types of solid tumors. The purpose of this study was to assess the prognostic value of NLR in DLBCL patients. Methods: Patients with DLBCL (n = 47) were recruited, including 31 patients in remission and 16 patients with relapsed DLBCL. All patients received 6-8 cycles of R-CHOP. Clinical parameters were studied, including IPI and complete blood count before treatment and after each chemotherapy cycle. Results: IPI predicted unfavorable outcome in 3 (18.75%) patients with relapses, and favorable outcome and high treatment efficacy in 13 (81.25%) patients. Among patients in remission, IPI predicted unfavorable outcome in 2 (6.5%) patients and favorable outcome in 29 (93.5%) patients. NLR calculation showed 100% low treatment efficacy for patients with relapses (NLR =4.1±0.51). At the same time, NLR predicted favorable outcome in 22 (70.96%) patients in remission (NLR =1.9±0.20), and relapses in 9 (29.04%) patients (NLR =4.83±0.55). 7 (22.6%) of the patients at risk developed relapses within 6-10 months after good treatment effects. Conclusions: Thus, NLR can be used as a prognostic factor in patients with DLBCL.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e19501-e19501
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e14018-e14018
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
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