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Introduction: This study aimed to measure serum levels of 12 selected parameters in patients with monoclonal gammopathy of undetermined significance (MGUS) and initial, asymptomatic phase of multiple myeloma (MM) to assess their potential benefit in differentiating both conditions., Patient Sample and Methodology: The analysed sample of 131 patients consisted of 62 patients with MGUS and 69 patients with MM fulfilling the criteria of the International Myeloma Working Group (IMWG). The following techniques were used to assess serum levels: quantitative immunoradiometry (bone-type alkaline phosphatase - bALP and insulin-like growth factor-1 - IGF-1), chemiluminescent enzyme immunochemical reaction (parathormone--PTH), quantitative sandwich enzyme immunoassay (osteopontin--OPN, endostatin (ES), macrophage inflammatory protein-1alpha/beta--MIP-1alpha/beta, angiogenin--ANG a IL-17). Pearson chi2 test and Mann-Whitney U-test were applied during the statistical analysis., Results: The analysis showed statistically significant differences in serum concentrations between MGUS and symptomatic form of MM (Durie-Salmon (D-S) stage 2-3) for: albumin, beta2-microglobulin (beta2-M) and OPN (p = 0.0001 and < 0.0001); osteocalcin for stage 2 (p = 0.006) and MIP-1alpha for stage 3 patients (p = 0.0002). Using the International Staging System (ISS), statistically significant differences between MGUS and all stages of MM (1-3) were identified for albumin and OPN (p = 0.003 and 0.001 and 0.00009, respectively), stages 2 and 3 for beta2-M and ES (p = 0.015 and 0.0001, respectively), stage 2 for ANG (p = 0.014) and stage 3 for MIP-1alpha (p = 0.00001). Statistically significant differences between MGUS and initial, asymptomatic phase of MM (D-S stage 1) was found only for bALP (p = 0.01) and for albumin (p = 0.004) and OPN (p = 0.003) when ISS was applied. Renal function impairment (D-S substage B) showed in comparison to MGUS significant elevation of serum levels of beta2-M (p < 0.0001), OC (p = 0.011), IGF-1 (p = 0.014), OPN (p = 0.003), ES (p = 0.0001), MIP-1alpha (p = 0.0004) and ANG (p = 0.005) and for albumin (p < 0.0001), beta2-M (p < 0.0001) and OPN (p < 0.0001) only when compared to substage A., Conclusion: Only albumin and OPN showed useful even though non-specific potential to differentiate MGUS from all ISS stages of MM, beta2-M and ES for ISS stages 2 and 3, the other parameters differed for stage 2 (ANG), stage 3 (MIP-1alpha) only and stage 1 (bALP), stage 2 (OC) and stage 3 (MIP-1alpha) when D-S stratification was applied.

Backgrounds: The aim of the study was to evaluate the serum levels of 18 selected parameters in monoclonal gammopathy of undetermined significance, and the initial, asymptomatic phase of multiple myeloma, also from the point of view of the potential contribution to the differentiation of these two units., Materials and Methods: The analyzed 119-patient group consisted of 59 individuals with monoclonal gammopathy of undetermined significance and 60 patients with multiple myeloma assessed at the time of diagnosis before the start of the treatment. For the evaluation of serum levels we used radioenzyme assay (thymidine kinase), immunoradiometry (IGF-1), enzyme immunoassay (osteocalcin, osteoprotegerin, ICTP), electrochemiluminiscence (PINP), quantitative sandwich enzyme immunoassay (MIP-1 alpha and MIP-1 beta, IL-17, osteopontin, HGF, VEGF, angiogenin, endostatin, syndecan-1/CD138), and for the assessment of serum levels of free light chains kappa and lambda, the Freelite system. Statistical evaluation was done using the Pearson chi-quadrat test and the U-test according to Mann-Whitney (p < 0.05)., Results: Statistically significant differences between monoclonal gammopathy of undetermined significance and multiple myeloma were found in the case of serum levels of thymidine kinase (0.0002), ICTP (0.001), MIP-1 alpha (0.002), osteopontin (<0.0001), HGF (< 0.0001), syndecan-1 (<0.0001), and the kappa/lambda ratio (0.0002), while lower significance was found in the case of angiogenin (0.031) and endostatin (0.011). Statistically non-significant differences between multiple myeloma and monoclonal gammopathy of undetermined significance were within the serum levels of IGF-1, osteocalcin, bALP, PINP, OPG, MIP-1 beta, IL-17, parathormon and VEGF., Conclusion: Statistical analysis revealed significant differences between monoclonal gammopathy of undetermined significance and multiple myeloma in 9 of the 18 evaluated parameters. However, due to the significant overlapping of the measured values, none of the parameters is unambiguously able to distinguish between the units. A certain contribution in the discrimination of multiple myeloma from monoclonal gammopathy of undetermined significance was found in markedly increased serum levels of thymidine kinase, MIP-1 alpha, osteopontin, HGF and significant pathology of the kappa/lambda index.

Background: The aim of the study was the evaluation of serum levels of 12 selected biomarkers in monoclonal gammopathy of undetermined significance (MGUS) and in initial, asyptomatic phase of multiple myeloma, especially from the view of potential differentiation of these conditions in clinical practice., Methods and Results: Analyzed group of 268 individuals consisted of 89 individuals with MGUS and 179 patients with MM examined in time of diagnosis before treatment initiation. For evaluation of serum levels were used following methods: radioenzymatic method (thymidinekinase), enzymatic immunoassay (beta2-M, IL-6R, ICAM-1, VCAM-1, ICTP, PINP and OPG) and quantitative sandwich enzymatic immunoassay (HGF, VEGF, syndecan-1/CD138 and Fas). Pearson's chi2-test and test according to Mann-Whitney were used for statistical evaluation (p < 0.05). Wide statistic differences in serum levels of analyzed markers in MGUS vs. MM were detected in case of beta2-M, TK, ICTP, OPG, HGF and syndecan-1 (p < 0.0001), lower differences in case of VCAM-1, PINP and VEGF (p = 0.003, 0.001 and 0.04), and without difference in case of Fas. Except for thymidinekinase (p = 0.014) and syndecan-1 (p = 0.001) was not detected statistically important contrast of measured values in MGUS individuals and in patients with initial, asymptomatic phase of MM (stage 1), but these markers cannot be used in clinical practice due to significant overlap of serum values. Continuous downgrade of serum values of VEGF due to degree of MM progression (stages 1-3 according to Durie-Salmon) was unexpected., Results: Although the significant differences in 9 of 12 evaluated serum levels of selected biomarkers in groups of MGUS and MM were seen, the results revealed that these markers are unprofitable to bring discriminatory potential capable of being used to distinguish between MGUS and initial, asymptomatic phase of MM.

Purpose of Study: The study focuses on evaluation of differences in serum levels of selected biological indicators in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), primarily from the viewpoint of potential asset to clinical practice., Patients and Methodology: The analyse set of 96 patients consisted of 30 individuals with MGUS and 66 patients with MM examined in the context of the disease diagnosis before therapy commencement. Serum levels of the assessed parameters were examined with the help of radio-enzymatic method (thymidinkinase), radioimmunoanalysis (beta2-micro-globulin, ICTP, PINP), enzymoimmunoessay method (sIL-6R, sVCAM-1, sICAM-1, sOPG and sRANKL) and the technique of quantitative sandwich enzymatic immunoessay (sHGF, sVEGF, bFGF, syndecan-1/CD138 and sFas). Statistical examination was performed by Pearson and Fischer test, chi2-test, or nonparametric U-test pursuant to Mann-Whitney (p < 0.05)., Results: Statistically significant differences were found between MGUS and MM in the case of serum level comparisons of sIL-6R (p = 0.02), ICTP (p = 0.001), sHGF (p = 0.001) and syndecan-1/sCD138 (p = 0.001), while no statistically significant differences were present in the case of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. During the analysis of frequency of occurrence of abnormal values in the MM and MGUS groups, significant differences were found not only in the case of standard parameters, such as beta2-microglobulin, thymidinkinase, creatinin and albumin, but also in the case of sIL-6R, ICTP, sHGF and syndecan-1, but not in comparisons of the levels of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. Attempts at examination of serum levels of sRANKL and soluble form of bFGF failed as too low values were measured., Conclusion: The analysis of behaviour of the 10 parameters, mostly intimately related to biological properties of clonal plasmatic cells or to changes of microclimate of bone marrow, effectively contributed to distinction between MGUS and MM only in the case of serum levels of sIL-6R, ICTP, sHGF and syndecan-l (sCD138), i.e. indicators with demonstrable relevance for MM prognosis assessment.

Bone marrow plasma cells from patients with multiple myeloma express monoclonal cytoplasmic immunoglobulin, strongly express CD38 and usually coexpress CD56 and CD54. The aim of this study was to learn the relationship between the number of CD38+CD56+ and CD38+CD54 positive cells in peripheral blood with the activity of multiple myeloma. We evaluated the number of these cells in patients with monoclonal gammopathy and in the control group, as well. We used the two-color flow cytometry for this purpose. The peripheral blood of 57 patients with multiple myeloma and 4 patients with monoclonal gammopathy of unknown significance was repeatedly analyzed. Patients with high activity of multiple myeloma had the highest percentage of CD38+CD56+ and CD38+CD54+ cells. Patients with lower activity of the disease had lower count of these cells. But in 4 (11%) patients with high disease activity the count of CD38+CD56+ cells was zero. We conclude, that the longitudinal flow cytometric analysis of CD38+CD54+ and CD38+CD56+ cells is a useful method for estimation of disease activity in patients with multiple myeloma. Single analysis of these parameters cannot be used as a strict criterium for differential diagnosis.

We have investigated the possible interaction of paraprotein (pp) with anticoagulation mechanisms and fibrinolysis. Eighty four patients with monoclonal gammapathy (MG) were included to the study, 59 of them with multiple myeloma (MM). In 48.8% cases some defect was found. Decreased levels of antithrombin III (AT III) was observed in 13.3%, protein C (PC) in 18.3% and protein S (PS) in 13.5% of patients. Distribution between the free and the bound PS fraction remained normal. The most frequent abnormality found was the reduction of plasminogen (PLG) activity, which was observed in 35.1% and elevated levels of plasminogen activator inhibitor, detected in 42.3% of cases, respectively. Decreased plasminogen activator activity was observed in only one patient. The relationship between isotype and concentration of paraprotein and frequency of factor levels abnormalities was not found. The incidence of arterial and/or venous thrombosis was higher in patients with laboratory defect in comparison with the unaffected, however, the difference was not statistically significant. In contrast, the incidence of hemorrhagic complications was significantly lower in these patients (p < 0.01), although in most of them simultaneous defect of plasmatic coagulation and/or platelet functions was detected. We suggest, the interaction with both hemostatic and anticoagulation systems could result to "elimination" of inauspicious effect of pp on hemostasis. The impairment of anticoagulation systems and fibrinolysis is another type of paraprotein interference with hemostasis. It is also considered to be another pathogenetic mechanism of secondary deficiency of AT III, PC, PS and PLG.

The authors investigated haemostatic parameters of 43 patients with monoclonal gammapathy with principal diagnosis of multiple myeloma (MM-35), non-Hodgkin's lymphoma (NHL-3), M. Waldenström (3) and monoclonal gammapathy of undetermined significance (MGUS-2). Primary haemostasis defect was found in 24 patients. With the exception of 2 thrombocytopenic patients, the defect of aggregation, procoagulant activity and retraction is supposed to be caused by paraprotein. The examination of the 14C 5-HT release and TX B2 synthesis in thrombocytes showed, that platelet activation is unaffected and the paraprotein interferes with interactions of thrombocytes or with coagulation system. In plasma coagulation system explicit abnormalities were found only in thrombin time in 12 patients. The more detailed examination disclosed, that the defect resulted from paraprotein interference with fibrin monomer polymerisation. The thrombin proteolytic activity remained unaffected. In 3 patients shortened euglobulin lysis time was observed. Laboratory haemostasis defect was found in 26 patients (60%), however, the bleeding symptoms manifested in 5 cases (11%) only. The analysis of study results showed, that the most important abnormalities leading to overt bleeding are thrombocytopenia or combined haemostasis defect. Isolated laboratory defects remained silent in most cases.

The authors evaluated in a group of 89 patients with monoclonal gammapathy (18 patients with monoclonal gammapathy of undermined significance, 34 patients examined at the time of diagnosis of multiple myeloma (MM) and in a group of 71 patients with MM examined in different stages of the disease) the serum beta 2-microglobulin. It was revealed that the mentioned indicator is of no differential diagnostic value, it is not related to sex nor to the immunochemical type of monoclonal immunoglobulin. A relationship of serum beta 2-microglobulin to age, serum urea and serum creatinine, to the severity of anaemia, serum albumin, sedimentation rate of red cells, degree of infiltration of bone marrow by myeloma plasmocytes and the stage of the disease, evaluated by the systems of Durie-Salmon and Medical Research Council, was found. The authors tested the importance of serum levels of this indicator for the prognosis of the disease.