[Analysis of serum levels of Dickkopf-1 (DKK-1) in monoclonal gammopathy of undetermined significance and multiple myeloma]. / Analýza sérových hladin Dickkopf-1 (DKK-1) u monoklonální gamapatie nejistého významu a mnohocetného myelomu.

BACKGROUND: Several recent studies aim at the detection of biological parameters that enable more precise diagnostics and stratification of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). The objective of our study was to assess the potential contribution of serum levels of Dickkopf-1 (DKK-1) in MGUS and MM from the point of more specific differentiation of both conditions, and the relationship of DKK-1 to selected laboratory parameters, individual forms and clinical stages of both conditions. METHODS AND RESULTS: The analyzed cohort consisted of 46 individuals with MGUS and 152 patients with MM at the time of diagnosis. For the assessment of serum levels of DKK-1 we used ELISA method. We assessed also serum levels of free light chains (FLC) κ and λ using the Freelite system, and ß2-microglobulin (ß2-M) using the Immulite 1000 method. For statistical estimation we used: Pearson χ2-test, U-test according to Mann-Whitney and Kruskal-Wallis test. Our analysis revealed that there was no significant difference between the levels of DKK-1 in MGUS risk groups (0-3) and between the states with different FLC concentration including the κ/λ index of monoclonality. In MM there was a significant relationship of DKK-1 to the level of hemoglobin (p<0.008) but not to the levels of FLC, creatinine or ß2-microglobulin. Within the Durie-Salmon staging system, there were significant differences of DKK-1 between the stages I vs. III (p=0.001) and I vs. II+III (p=0.002). In the International Staging System (ISS) there were significant differences only between stages 1 vs. 2+3 (p=0.045). Although there was no overall significant difference of DKK-1 levels between MGUS and MM, there was a difference between MGUS vs stage III (p=0.001) and II+III (p=0.001) according to Durie-Salmon, and also MGUS vs. stage 2 (p=0.005) and vs. stages 2+3 (p=0,012) according to ISS. There were no significant differences in DKK-1 between MGUS and initial/asymptomatic form of MM (stage I). CONCLUSION: Although there was a significant difference of serum levels of DKK-1 between MGUS and initial/asymptomatic stage of MM when compared to advanced stage MM, and in patients with different Hb levels, we do not find the evaluation of serum levels of DKK-1 useful for routine discrimination of MGUS and MM, and for the specification of temporary stratification systems.

[Bortezomib-based therapy in patients with light chain deposition disease]. / Lécba bortezomibem u pacientu s onemocnením z depozice lehkých retezcu imunoglobulinu.

Light chain deposition disease (LCDD) is a rare systemic condition caused by monoclonal proliferation of terminally differentiated B-lymphocytes with production of free light chains and their deposition in kidneys or other organs. The aim of our study is to show the pitfalls of the diagnostics, and to demonstrate the effect of bortezomib-based therapy on a series of 4 patients with LCDD, from the point of hematological and organ therapeutic response. We include that bortezomib based treatment provides rapid and effective hematological response. It is, however, often accompanied by adverse events, especially within intensive treatment schedules. The most serious adverse effects includes peripheral neuropathy, which might be dose or treatment-limiting. Less intensive regimens ("bortezomib weekly") suggest an alternative with expectation of lower incidence of adverse effects. Autologous stem cell transplantation is a recommended and relatively safe approach in convenient candidates. Organ response is significantly delayed after hematological response, and organ damage by light chain deposits might not be fully reversible.

The relationship between some soluble osteogenic markers, angiogenic cytokines/other biological parameters and the stages of multiple myeloma evaluated according to the Durie-Salmon and International Prognostic Index stratification systems.

BACKGROUND: The aim of the present paper was to examine the correlation between serum concentrations of 12 soluble biological markers and stages of myeloma evaluated according to the Durie-Salmon (D-S) and International Prognostic Index (IPI) stratification systems. METHODS: We analyzed a non-pretreated group of 179 patients with MM stratified according to D-S and IPI. Serum levels of soluble biological markers were evaluated using ELISA, REA and quantitative sandwich enzymatic immunoassays. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: The staging system according to D-S revealed a highly significant relationship between all stages (I-III) in case of beta(2)-m (p<0.0001) and sTK (p<0.001), in sICTP a significant difference was found only in stages II vs III (p<0.001) and I vs III (p<0.001), in case of sCD(138) (syndecan-1) in stages I vs II (p = 0.006) and I vs III (p<0.001), in sVEGF only in stages I vs III (p = 0.006). In substages A vs B we found a significant difference in case of beta2-m (p<0.0001), sTK (p = 0.041), sICTP (p 0.0001), sOSP (p = 0.008), sHGF (p<0.001), sCD138 (p = 0.001) and sFas (p= 0.001). The relationship between other factors and stages and substages according to D-S appeared nonsignificant. The IPI system showed a highly significant relationship between all 3 categories (1-3) in case of beta(2)-m (p<0.001), sTK (p<0.0001) and sICTP (p<0.0001), while in sHGF only in stages 2 vs 3 (p<0.0001) and 1 vs 3 (p<0.0001). In 4 parameters there were only discrete differences in 1 vs 3: sPINP (p= 0.036), sOSP (p= 0.002), sCD(138) (p = 0.03) and sFas (p=0.012), in the remaining markers the analysis was negative. CONCLUSIONS: A highly convincing relationship between myeloma stages and serum levels was found only in beta(2)-m, sTK, sICTP and partly also in sCD(138) (syndecan-1) and sHGF. More favourable was the IPI stratification system.