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  • 1
    In: Journal of Modern Oncology, Consilium Medicum, Vol. 24, No. 1 ( 2022-04-30), p. 80-88
    Abstract: Aim. To assess effectiveness and safety of Extimia BIOCAD (INN: empegfilgrastim) used to decrease the rate and duration of neutropenia, the rate of febrile neutropenia and infections that manifest in febrile neutropenia in patients with lymphoproliferative diseases who receive myelosuppressive therapy. Materials and methods. The paper presents the results of the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study of effectiveness and safety of Extimia BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases who receive cytotoxic therapy. The second stage of the interim analysis describes patient characteristics, therapy used in 221 patients with morphologically confirmed lymphoma who received one or more cycles of chemotherapy as part of LEGERITY study. The endpoints of interest included the rate of Grade 3/4 neutropenia in patients, after the first cycle of any therapy line; the rate of febrile neutropenia; the rate of Grade 3/4 infectious complications; the rate of antibacterial therapy prescriptions; and the assessment of the relative dose-intensity of received chemotherapy. Additionally, the incidence rate of all adverse drug reactions (ADRs) was assessed in patients who received at least one dose of the study drug; the incidence rate of all serious ADRs was assessed in patients who received at least one dose of the study drug; the incidence rate of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Grade 3/4 ADRs in patients who received at least one dose of the study drug; the rate of study drug discontinuations due to ADRs was also assessed. Results. As of the second interim analysis, LEGERITY included 221 patients with various indolent and aggressive lymphomas. Median age of the patients was 53 years (1982). A group of older patients (over 60 years of age) accounted for 34% of the study population. Patients received 1 injection of Extimia per chemotherapy cycle. Grade 3/4 neutropenia was registered in 6.7% (n=14) patients. Overall, all-grade neutropenia was reported in 21.4% (n=44) patients. Febrile neutropenia was reported in 2.9% cases. Severe infections and the use of antimicrobials were reported in no patients throughout the CT period and after each cycle of therapy. Most commonly reported adverse reactions included mild-to-moderate ossalgias (6.8%) and myalgias, back pain, and arthralgias (3.2%), that did not require pharmaceutical therapy. One (0.5%) patient had a severe adverse drug reaction a CTCAE 5.0 Grade 4 hypotension episode. Conclusion. Interim analysis results support high effectiveness and safety of the Russian original pegylated granulocyte colony-stimulating factor of empegfilgrastim (Extimia) in patients both with indolent and aggressive lymphomas. Real world evidence demonstrates a favourable safety and tolerability profile of empegfilgrastim in all age groups, including in the aging population. As of the moment of the interim analysis publication, the study is ongoing. Final conclusions on the safety and effectiveness of empegfilgrastim (Extimia) are to be drawn upon the study completion.
    Type of Medium: Online Resource
    ISSN: 1815-1442 , 1815-1434
    Language: Unknown
    Publisher: Consilium Medicum
    Publication Date: 2022
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  • 2
    In: I.P. Pavlov Russian Medical Biological Herald, ECO-Vector LLC, Vol. 28, No. 1 ( 2020-04-09), p. 44-56
    Abstract: Aim. To study the prevalence of carriage of polymorphic allele variants of genes of blood coagulation factors in oncological patients. Materials and Methods. 213 Patients with morphologically confirmed oncological diseases were examined. Samples of genomic DNA of peripheral blood of the patients were examined. Using polymerase chain reaction (PCR), polymorphic sites of genes of hemostatic system were studied in real time: F2 (G20210А, rs1799963), F5 (G1691A, rs6025), F7 (G10976A, rs6046), F13 (G226A, rs5985), FGB G(-455)A (rs1800790), ITGA2-2 (C807T, rs1126643), ITGB3-b (Т1565С, rs5918), PAI-1 4G(-675)5G, rs1799889). Results. The prevalence of carriage of alternative allele of F2 (G20210А) polymorphic locus in the studied group was 1.6%, of F5 (G1691A) 3.5%, of F7 (G10976A) 13.4%, of F13 (G226A) 28.2%, of FGB G(-455)A 24.9%, of ITGA2-2 (C807T) 41.5%, of ITGB3-b (Т1565С) 15.5%, of PAI-1 4G(-675)5G 56.6%. A statistically significant increase in the frequency of risk alleles of F5 G1691A (р=0.0169), F13 G226A (р=0.0007), FGB G(-455)A (р0.0001) and ITGA2-2 C807T (р=0.0201) polymorphic loci was found in oncological patients as compared to the general population. In the same loci, except ITGA2-2 (C807T), statistically significant differences in the frequency of alternative alleles were found in different localizations of the oncological process. In 92.0% of patients, SNR combination was determined in different components of hemostatic system. Conclusion. Taking into account a high frequency of identification of risk alleles in all components of hemostatic system, it is reasonable to carry out additional research to determine the necessity of addition of antiaggregants to antithrombotic therapy in oncological patients.
    Type of Medium: Online Resource
    ISSN: 2500-2546 , 0204-3475
    URL: Issue
    Language: Unknown
    Publisher: ECO-Vector LLC
    Publication Date: 2020
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  • 3
    Online Resource
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    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. e19500-e19500
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e19500-e19500
    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
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e19511-e19511
    Abstract: 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.
    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: 2017
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e20086-e20086
    Abstract: 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±0.06×10 12 /L with B19V and 4.57±0.08×10 12 /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±3.44×10 9 /L, after CT – 10.6±2.7×10 9 /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.
    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: 2020
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e19510-e19510
    Abstract: 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.
    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: 2017
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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. 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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  • 8
    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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    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. 40, No. 16_suppl ( 2022-06-01), p. e18055-e18055
    Abstract: e18055 Background: Epstein-Barr virus (EBV) is associated with the development of various cancers, including nasopharyngeal carcinoma (NPC), gastric cancer, and lymphomas. The use of EBV serological markers in screening and monitoring of NPC has been shown to be valuable. The significance of serological markers in the diagnosis of other head and neck cancers is poorly described. The aim of this study was to analyze the serological profiles of EBV infection in patients with head and neck tumors. Methods: The main group included 24 patients with laryngeal cancer (n = 12) and oral mucosa cancer (n = 12). Keratinizing squamous cell carcinoma was registered in 22 (91.7%) patients, and adenoid cystic cancer in 2 (8.3%) patients. The control group included 44 lymphoma patients. Antibodies to EBV proteins were determined in the blood serum by ELISA and Western blot (WB) tests. Results: ELISA detected antibodies of the A, M and/or G classes against various EBV proteins in 100% of patients in the main group and 97.7% of controls. IgA VCA in patients with head and neck cancer were determined 2.7 times more often (50% vs 18.2%, p = 0.034) than in patients with lymphomas, IgG EA - 2.1 times more often (58.3% vs 27.3%, p = 0.049), and the complex of acute infection markers (IgA VCA, IgM VCA, IgG EA in various combinations) was determined 2.0 times more often (66.7% vs 34.1%, p = 0.045). Atypical profile (only VCA IgG+) was determined only in patients with lymphomas (4.5%). The profile characteristic of immunosuppression (IgG VCA+, IgG EA+, NA IgG±) was determined 1.8 times more often in patients with head and neck cancer than in patients with lymphomas (25% vs 13.6%, p 〉 0.05). According to WB tests, patients of the main group more often demonstrated IgM EBNA-1p79 (16.7%), VCA p65 (16.7) and p22 (16.7%), while controls – VCA p22 (27.8%), EA-R p93 (16.7%) and VCA p33 (16.7%). IgG in the main group was more often determined to EBNA-1 p79 (91.7%), VCA p22 (91.7%) and VCA p33 (66.7%), in the control group to VCA p40 (87.5%), EBNA-1 p79 (75%) and VCA p22 (62.5%). Statistically significant differences were found only for VCA p42 (0% in the experimental group and 37.5% in controls, p = 0.049), VCA p40 (25% and 87.5%, p = 0.009) and p27 (0% and 37.5%, p = 0.049). EA-D p45 was determined only in patients with lymphoma. Conclusions: The vast majority of patients in both groups were previously infected with EBV. Serological profiles of EBV infection in patients with head and neck cancer and lymphomas were significantly different. Markers of acute infection were more often determined in patients with head and neck cancer; the range of individual proteins in the main group was narrower than in the control group. The biological meaning of the differences in the detection rates of antibodies to individual EBV proteins in patients of the two groups remains to be elucidated.
    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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  • 10
    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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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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