REVIEW OF THE NATURE OF ANTI/INFLAMMATORY AND PRO-INFLAMMATORY CYTOKINE REGULATION IN DIFFERENT PERIODS OF PLASMA CELL MYELOMA NATURAL HISTORY IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / АНАЛІЗ ХАРАКТЕРУ РЕГУЛЯЦІЇ ПРОТИЗАПАЛЬНИХ І ПРОЗАПАЛЬНИХ ЦИТОКІНІВ НА РІЗНИХ ЕТАПАХ ПЕРЕБІГУ ПЛАЗМОКЛІТИННОЇ МІЄЛОМИ У ХВОРИХ, ЯКІ ПОСТРАЖДАЛИ ВНАСЛІДОК АВАРІЇ НА ЧОРНОБИЛЬСЬКІЙ АЕС.

OBJECTIVE: identify the nature of anti-inflammatory and pro-inflammatory cytokine regulation in different periods of plasma cell myeloma (PCM) natural history with evaluation of its role as a prognostic criterion for the disease course in the Chornobyl NPP (ChNPP) accident survivors. MATERIALS AND METHODS: Levels of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines both with their relationship were studied in the stage I-II and stage III PCM patients (n = 74) in different periods of the disease natural history i.e. remission/stabilization and progression. Study groups included the ChNPP accident survivors (n = 35) and non-irradiated subjects (n = 39). Immunoenzymatic method was applied using the Vector-Best CJSC commercial kits. RESULTS: There was a unidirectional increase in the levels of IL-6, TNF-α, and IL-10 in irradiated persons, and an elevation of IL-6 and TNF-α concentration but with a decreased level of IL-10 in non-irradiated subjects compared to control at the time of PCM diagnosis. Period of the disease remission/stabilization in PCM stage I-II patients featured a decrease in IL-6 concentration regardless of the exposure to ionizing radiation, while TNF-α content remained at the level of the control group. There was a significant increase in IL-6 concentration in both study groups during the disease relapse, while TNF-α level remained unchanged compared to stabilization phase of the disease. According to the obtained data a certain contribution of radiation exposure to the PCM pathogenesis as a possible predictor of the exacerbated disease course cannon be excluded. CONCLUSION: Determining the serum level of pro-inflammatory and anti-inflammatory cytokines (IL-6, TNF-α and IL-10 respectively) provides advancement in assessment of the PCM course and predict the effectiveness of administration of therapy protocols.

COMPLEX ANALYSIS OF THE ROLE OF CYTOKINE GENE POLYMORPHISMS AS PROGNOSTIC FACTOR OF THE RISK OF PLASMA CELL MYELOMA IN PERSONS SUFFERED AFTER THE CHORNOBYL NPP ACCIDENT. / KOMPLEKSNYI ANALIZ ROLI POLIMORFIZMU GENIV TsYTOKINIV IaK PROGNOSTYChNOGO ChYNNYKA RYZYKU PLAZMOKLITYNNOÏ MIIeLOMY U OSIB, POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChORNOBYL'S'KII AES.

OBJECTIVE: to provide a comparative characterization of the prevalence of polymorphic variants of cytokine genes in plasma cell myeloma (PCM) patients suffered after the Chornobyl disaster and patients who were in contact with ionizing radiation within the natural radiation background, based on comparison with population controls to determine their contribution as genetic markers of disease risk. MATERIALS AND METHODS: Molecular genetic studies of polymorphism of cytokine genes (TNF-α, TGF-ß1, IL-6, IL-10, IFN-γ) and complex frequency analysis of occurrence in three-, four-, and five-locus combinations of their allelic variants as prognostic markers of the risks of plasma cell myeloma was carried out in 102 patients - 56 victims of the Chornobyl nuclear power plant accident and 46 patients irradiated within the limits of the natural radiation background, in comparison with the control group (364 practically healthy people, residents of the Central geno-geographical region of Ukraine). RESULTS: The same probable increase in the prevalence of the TGF-ß genotype codon10 T/T of the TGF-ß1 gene was established in the groups of patients irradiated after the Chornobyl NPP accident and non-irradiated patients. In patients with plasma cell myeloma a protective effect for IL-10 -1082 A/G and an association with the risk of disease occurrence for IL-10 -1082 G/G were determined. CONCLUSION: Probable difference in the frequency of the TGF-ß1 genotype codon10 T/T of the TGF-ß1 gene in the observed groups relative to the control group provides grounds for considering this single-nucleotide polymorphism of the TGF-ß1 gene as an immunogenetic factor of predisposition to the development of PCM independent of exogenous factors. The study of the contribution of multigene combinations of «gene-gene¼ interaction indicates their role in the mechanisms of plasma cell myeloma occurrence and confirms the presence of an additive interaction.

EFFICIENCY OF BONE MARROW PRECURSOR CELL COLONY-FORMING AS A PREDICTOR OF DISEASE COURSE IN PLASMA CELL MYELOMA PATIENTS WITH A HISTORY OF RADIATION EXPOSURE. / EFEKTYVNIST' KOLONIIeUTVORENNIa KLITYN-POPEREDNYKIV KISTKOVOGO MOZKU, IaK PROGNOSTYChNYI FAKTOR PEREBIGU PLAZMOKLITYNNOÏ MIIeLOMY U OSIB Z RADIATsIINYM ANAMNEZOM.

OBJECTIVE: Assessment of role of the bone marrow colony-forming efficiency in plasma cell myeloma patients at different stages of treatment as a prognostic criterion for the disease course. MATERIALS AND METHODS: The colony forming efficiency (CFE) was assayed in stage I-II plasma cell myeloma (PCM)patients (n = 37) aged 42-73, namely in patients survived after the Chornobyl NPP accident (n = 21) and persons notexposed to ionizing radiation (n = 16). There were 11 males exposed to ionizing radiation and having got stage I PCM,9 males and 3 females exposed and having got stage II PCM, 3 males and 3 females not exposed and having got stageI PCM, 6 males and 2 females not exposed and having got stage II PCM. Healthy persons (n = 20) were included in thecontrol group. RESULTS: Number of the bone marrow (BM) granulocyte-macrophage colony-forming units (CFU-GM) in both exposedand not exposed PCM patients depended on a disease stage. CFU-GM was (16.7 ± 1.2) in the stage I PCM patients vs.(11.1 ± 1.1) in the stage II PCM ones both being lower (p < 0.05) compared to control (64.5 ± 2.2). Changes in cluster formation were similar, i.e. (37.7 ± 1.6) and (19.4 ± 1.3) correspondingly in the stage I and stage II PCM patients.Respective values in control were (89.8 ± 3.6). The CFE in stage I and stage II PCM patients at the time of diagnosiswas lower (5.7 ± 1.5 and 2.4 ± 1.1 respectively) vs. control (39.5 ± 1.51, p < 0.05), but has increased in remission upto (29. 6 ± 1.8) and (13.8 ± 1.2) respectively. There was no difference at that between the irradiated and non-irradiated patients. Number of the fibroblast colony-forming units (CFU-F) in the stage I and stage II PCM patients duringdiagnosis, namely (43.9 ± 5.4) and (22.5 ± 3.7), was lower (p < 0.05) vs. control (110.5 ± 4.9). Upon reaching remission the CFU-F value increased significantly (p < 0.05), reaching (87.4 ± 4.2) and (55.6 ± 2.7) correspondingly in thestage I and stage II PCM patients. CONCLUSION: Dependence of the BM cell CFE on the stage of PCM and presence or absence of remission was established. Prognostic value of the CFE of BM CFU-GM in terms of life span of patients was shown (Ro Spearm = 0.39,p < 0.02), namely in case of CFE > 20 before the polychemotherapy administration the life span of PCM patients wassignificantly longer vs. cases of CFE < 20.

IMMUNOGENETIC AND PHARMACOCHEMICAL CHARACTERIZATION OF THE ABO SYSTEM GLYCOPROTEIN PROPERTIES AS CRITERIA OF INDIVIDUAL SENSITIVITY TO ANTITUMOR AGENT BORTEZOMIB IN THE PLASMA CELL MYELOMA PATIENTS. / IMUNOGENETYChNYY̆ TA FARMAKOKhIMIChNYY̆ ANALIZ VLASTYVOSTEY̆ GLIKOPROTEÏNIV SYSTEMY AVO IaK KRYTERIÏV INDYVIDUAL'NOÏ ChUTLYVOSTI ShchODO PROTYPUKhLYNNOGO PREPARATU BORTEZOMIBU U KhVORYKh NA PLAZMOKLITYNNU MIIeLOMU.

OBJECTIVE: Experimental study of the effect profile of bortezomib in the plasma cell myeloma (PCM) patients depend- ing on a specific phenotype carrier state and a pharmacochemical characteristics of ABO system glycoproteins. MATERIALS AND METHODS: The research was conducted on the 104 PCM patients, including the Chornobyl NPP acci- dent survivors (n = 49) and 65 study subjects in the comparison group. Immunogenetic criteria for positive response to the applied treatment protocols were issued according to the duration of remission, absence of infectious com- plications, and evidence of chronic renal failure as a disease complication. RESULTS: Possibility of glycoproteins A and B participation in the formation of human biological individuality at a level of protein-protein interaction with antineoplastic drug bortezomib, which is widely used in cancer management prac- tice, in particular in the PCM treatment is considered. The glycoprotein B was shown being a selective target for borte- zomib, slowing down the recognition and interaction of antigen B with monoclonal anti-B antibody, while the agglu- tination period lengthens at that by 66 %. Assumption that the formation of bortezomib complex with glycoprotein B provides a background for interaction with the key reaction of proteasome 26S inhibition, which to some extent con- tributes to the drug effect retardation was confirmed through the quantum-chemical calculations. Equilibrium is shift- ed toward the main reaction leading to a higher drug efficacy in patients with blood groups O (I) and A (II). CONCLUSIONS: Since the complexation occurs predominantly in alkaline medium the administration of drugs with alkaline reaction should be restricted for at least round the clock after administration of bortezomib according to its half-life in plasma in patients with B (III) blood group and chronic renal failure.

CLINICAL, HEMATOLOGICAL CHARACTERIZATION AND POLYMORPHISM OF ABO AND Rh BLOOD GROUP SYSTEMS IN PLASMA CELL MYELOMA PATIENTS. / KLINIKO-GEMATOLOGIChNA KhARAKTERYSTYKA TA POLIMORFIZM SYSTEM GRUP KROVI AVO TA Rh U KhVORYKh NA PLAZMOKLITYNNU MIIeLOMU.

Objective to study the peculiarities of clinical characteristics and polymorphism of ABO and Rh blood group systemsin relation to the natural history of plasma cell myeloma in the ChNPP accident survivors. MATERIALS AND METHODS: Peculiarities of the disease natural history were reviewed in the 111 plasma cell myeloma(PCM) patients receiving medical management at the Department of Radiation Oncohematology of the NRCRM dur-ing 2010-2017. Principal clinical and laboratory characteristics of PCM, namely the values/levels of LDH, ß2-mic-roglobulin, albumin, serum calcium, urea, creatinine and hemoglobin were assessed, taking into account the gender,radiation history (ChNPP accident clean-up workers, evacuees from areas of obligatory resettlement, inhabitants ofcontaminated territories, and the comparison group) and the PCM stage codenamed by Durie-Salmon et al. (1975)and the ISS (1985) classifications. Distribution of polymorphic variants on ABO and Rh blood systems was studiedin the 106 PCM patients. RESULTS: It was found that the level of ß2-micro-globulin and calcium was increased significantly in male (p = 0.02and p = 0.04, respectively), whereas serum urea content was elevated in female (p = 0.04) PCM patients featuring acompromised radiation anamnesis in comparison to non-irradiated patients. Some probable differences were foundfor urea level (F = 3.58, p = 0.05) and serum albumin (F = 4.00, p = 0.05) in the examined group of PCM patients.Probable (p < 0.05) incidence increase of the B phenotype was established as a predictor of complicated natural his-tory of PCM with abnormal genetic equilibrium resulted from the increased incidence of IB allele in chronic renal fail-ure (CRF) patients. Significant (p < 0.05) prolongation of the remission period upon a standard PCT application wasfound in PCM patients being the A phenotype carriers having a preserved gene and phenotypic equilibrium comparedwith carriers of O and B phenotypes. CONCLUSIONS: Clinical and hematological parameters are different in PCM patients survived after the ChNPP accidentand those with favorable radiation history. Distribution of polymorphic variants of ABO antigenic structures inpatients with complicated natural history of the disease is also different, that can be a background for predictingthe effectiveness of treatment. Further research is required in this field.

CASE OF DEVELOPMENT OF NON-HODGKIN'S MALIGNANT LYMPHOMA ON THE BACKGROUND OF CHRONIC MYELOID LEUKEMIA IN A PATIENT WHO SUFFERED OF THE CHORNOBYL ACCIDENT. / VYPADOK ROZVYTKU NEKhODZhKINS'KOÏ ZLOIaKISNOÏ LIMFOMY NA FONI KhRONIChNOÏ MIIeLOÏDNOÏ LEIKEMIÏ U PATsIIeNTKY, IaKA POSTRAZhDALA VNASLIDOK AVARIÏ NA ChAES.

In this paper, a clinical case of combination of chronic myeloid leukemia and T-lymphoblastic lymphoma is present-ed, which is currently a rather rare finding for a clinician. The diagnosis of T-lymphoblastic lymphoma is establishedafter 2 years from the verification of chronic myeloid leukemia. The course of diseases and approaches to treatmentare described.The pathogenetic relationship between myeloid and lymphoid diseases remains unclear and is likely to be the resultof several factors - radiation, chemical and, consequently, genetic disorders.