Abstract: Wild-growing edible mushrooms are valuable food with a high content of proteins, fibers, antioxidants, and they are characterized by their specific taste and flavor. However, from an ecotoxicological point of view, they are a risk commodity because of their extremely high bioaccumulative capacity to accumulate the risk elements and contaminants from the environment. In the present study, we examined mercury (Hg) contamination in 230 fruiting bodies of Macrolepiota procera (Scop.) Singer and 230 soil/substrate samples, which were collected in foraging seasons 2015–2019 from 22 different locations in Slovakia. Total mercury content was determined by cold-vapor AAS analyzer AMA 254. The level of contamination and environmental risks were assessed by contamination factor (Cf), index of geoaccumulation (Igeo), and potential environmental risk index (PER). Bioaccumulation factor (BAF) was calculated for individual anatomical parts of M. procera. Mercury content in the soil/substrate samples varied between 0.02 and 0.89 mg kg−1 DW, and in mushroom samples between 0.03 and 2.83 mg kg−1 DW (stems), and between 0.04 and 6.29 mg kg−1 DW (caps). The obtained results were compared with the provisional tolerable weekly intake for Hg defined by WHO to determine a health risk resulting from regular and long-term consumption of M. procera.

Abstract: Grapes and wine are important sources of antioxidants in human diet. Phenolic substances contained in grapevine berries belong to an important group of natural substances that get into wine in the process of wine making. Polyphenols and flavonoids are primarily accountable for the colour and taste of the wine, they affect the perception of bitterness and acerbity. They also have antioxidant properties, thus have a positive effect on human health. Health benefits of polyphenolic substances from wine may be associated with a wide range of biological processes. Thanks to the development of modern analytical methods, wine is constantly being researched in terms of the content of antioxidants, and its importance to human health. Sixteen Slovak white wines of Muscat type produced in different geographical regions were analysed in this study. The object of this work was to determine total polyphenol content and total flavonoid content, and to evaluate antioxidant effects of quality wines of Muscat varieties produced in Slovakia. Antioxidant activity, total polyphenol content, and total flavonoid content of particular wines is described in the study. Studied characteristics were analysed by UV-VIS spectrometry method. Muscat wines showed weak to high antioxidant activity, ranging from 25.2% inhibition of DPPH to 67.7% inhibition of DPPH. Average antioxidant activity was 38.7% inhibition of DPPH. Total polyphenol content in the Muscat type varietal wines varied from 262.1 GAE.L-1 to 568.3 GAE.L-1. Average total polyphenol content was 382.13 GAE.L-1. The content of total flavonoids in Muscat type varietal wines ranged from 24.8 mg CE.L-1 to 169.1 mg CE.L-1. Average total flavonoid content was 100.5 mg CE.L-1.

Abstract: Sweet potatoes are reported to be a good source of bioactive compounds. The aim of this study was to evaluate the impact of different heat treatment methods (microwaving, steaming, and baking) and variety on the total polyphenol content and antioxidant activity of three sweet potato varieties – Beauregard (orange-fleshed), O’Henry (white-fleshed), and 414-purple (purple-fleshed). All investigated parameters were determined spectrophotometrically. The total polyphenol content was in the range of 0.53 (O’Henry) – 5.60 mg GAE.g-1 DW (414-purple) for raw flesh and 1.68 (O’Henry) – 7.03 mg GAE.g-1 DW (414-purple) for raw peel of sweet potatoes. Heat treatments caused an increase of total polyphenol content in sweet potatoes (0.98 (steamed O’Henry) – 28.04 mg GAE.g-1 DW (baked 414-purple)). In terms of antioxidant activity, the steamed samples of variety 414-purple showed the highest values of DPPH radical scavenging activity (4.51 µmol TE.g-1 DW) and Ferric reducing antioxidant power assay (19.57 µmol TE.g-1 DW) compared to the other treatment methods. Spearman´s test showed a strong positive relationship between both used methods for evaluation of antioxidant activity. All studied processing methods positively affected the total polyphenol content and antioxidant activity in sweet potatoes.

Abstract: Benefit of maintenance and/or consolidation therapy after autologous transplantation (AT) is unclear. CMG 2002 is randomized phase III study comparing efficacy and safety of consolidation therapy versus interferon alfa (IFN) maintenance therapy after AT in patients with newly diagnosed multiple myeloma (MM). Methods: A total of 545 patients were enrolled to the trial in the period of April 2002 to April 2007. This first analysis (patients enrolled until December 31, 2005) was done in cohort of 269 patients randomly assigned after AT to either IFN 3x3 MU s.c. weekly alone (IFN group) until relapse or four cycles of chemotherapy CED (cyclophosphamide 300–400 mg/m2 i.v., etoposide 30–40mg/m2 i.v., and dexamethasone 40mg on days 1–4; month 4,8,12 and 16 after transplantation; CED group) followed by IFN 3x3 MU s.c. weekly starting month 18 after AT. All patients received primary therapy with four cycles of VAD regimen (vincristine, doxorubicine, and dexamethasone) followed by mobilization with cyclophosphamide 2.5g/m2 and G-CSF 5–10 μg/kg. The conditioning regimen with melphalan 200mg/m2 was used for single AT. Response was defined according to Blade’s criteria. Median of follow up is 41 months (range 6.2–56.1) Results: All basic parameters including median age, gender distribution, measures of disease burden, renal function and also response rate before/after AT, and basic prognostic factors (beta2microglobulin, albumin, LDH, CRP) were comparable between randomized IFN group (n=134) and CED group (n=135) as follows: median age 57.0 vs. 57.0; stage I: 8.1% vs. 5.5%, stage II: 27% vs. 27.3%, stage III: 64.9% vs. 66.7%; stage B 12.8% vs. 17.1%; ISS I: 37.2% vs. 34.0%, ISS II: 29.7% vs. 34.0%, ISS III: 17.6% vs.21.8%, ISS not available: 15.5 vs.10.2%; IgA: 25.7% vs. 29.9%, IgG: 61.5% vs. 51.8%; ORR after AT (CR+PR): 72.3% vs.72.1%, CR: 23.0% vs. 19.0%, VGPR: 17.6 vs. 24.5%, PR 31.8% vs. 28.6%). Four cycles of CED consolidation treatment after AT did not significantly increase response rate achieved after AT in comparison with IFN group (response rate improved in 14,8% in CED group vs. 15,1% in IFN group at 4 months, respectively in 81,5% vs. 75,8% at 18 months after AT). There was no significant difference between CED and IFN groups in time to progression [TTP] (median 34.5 vs.38.2 months, p=0.622), in progression free survival [PFS] (median 32.4 vs. 36.8 months, p=0.515) and also in duration of response [DOR] (29.6 vs. 36.2 months). Median of overall survival was not yet reached (25th percentile 40.8 months for all patients). CED consolidation had acceptable toxic profile. Conclusions: In the first analysis of CMG 2002 randomized phase III study consolidation therapy based on conventional chemotherapy and corticoids followed by IFN maintenance therapy did not show any benefit for patients if compared with IFN maintenance alone.

Abstract: Introduction: Collection of valid data in patients with hematologic malignancies remains a challenge. Especially low grade malignancies require long term follow-up and valid high quality data. The RMG registry was established in 2007 and has become one of the flagship projects of the Czech Myeloma group. To date, four parts of the registry are active - module for multiple myeloma (MM), monoclonal gammopathies of undetermined significance (MGUS), AL amyloidosis (ALA) and Waldeströms macroglobulinemia. The later two has been started in 2014. Aim: To analyze current status of the registry in terms of amount of contained data. Methods: All patients must sign a written consent before entering their data into the registry. Data concerning diagnosis, demography, treatment and survival are regularly collected and updated into the registry via online system at https://trials.cba.muni.cz/trialdb2/interface_forms/login_rmg.asp. The data from MGUS patients are retrospective and prospective, data from MM patients are only prospective (since 2007). Registry is regularly monitored and data are validated by an external monitor. Results: There are 22 participating centers as of July 2015 (18 from the Czech Republic and 4 from Slovakia). Data from 4549 patients with MM, 2168 with MGUS, 121 patients with WM and 22 with ALA have been collected. Together 6860 patients have been included in the registry as of July 2015. Median follow-up of MGUS patients is 4 years (0-35 years) and median follow-up for MM patients is 2 years (0-32 years). The huge amount of data allowed publication of treatment results of MM patients treated with bortezomid and thalidomide in the Czech Republic and regular analysis of patients treated with lenalidomide. Novel prognostic models for MGUS progression and asymptomatic myeloma have been created based on registry data (manuscripts submitted). Conclusion: The RMG is one of the largest registries in Europe. Its biggest advantage is collection of validated updated data which can be used to create rapid analyses in order to react to changing myeloma field. It helps us to create new guidelines and serves as a potent research tool. It can be also used to negotiate reimbursement with healthcare insurance companies and government regulatory authorities for novel drugs implementation into treatment standards. Supported by The Ministry of Education, Youth and Sports (Specific university research of the Faculty of Medicine, University of Ostrava) project no. SGS01/LF/2014-2015, by the Moravian-Silesian Region - grant no. MSK 02692/2014/RRC, by the Institutional Development Plan of University of Ostrava in 2015, financial resources are allocated by The Ministry of Education, Youth and Sports. Supported by grant NT14575. Disclosures Hajek: Amgen: Honoraria; Celgene: Consultancy; Janssen: Consultancy.

Abstract: Introduction: Revised prognostic scoring system R-ISS (standard ISS plus cytogenetic changes) has been introduced as a possible tool for evaluation of patients with multiple myeloma. This system is based on pooled data from various clinical trials but has not been validated in patients´ population outside the clinical trial setting. Aim: To evaluate clinical relevance of R-ISS in real life population of multiple myeloma patients. Methods: Registry of monoclonal gammopathies (RMG) was established in 2007 and has become one of the flagship projects of the Czech Myeloma Group. The registry collects prospective data from patients with myeloma and other gammopathies (https://trials.cba.muni.cz/trialdb2/interface_forms/login_rmg.asp). Registry is regularly monitored and data are validated by an external monitor. Data from registry were retrieved to identify patients in whom all above mentioned parameters were available. These patients were then stratified according to R-ISS and TTP and OS were calculated as primary endpoints. Results: 555 patients (260 females, 295 males, median age 66 years) with multiple myeloma who had full set of necessary data available were identified. Median follow-up of this cohort was 22.2 months. 97 17.5% (97/555) patients were R-ISS stage I, 55.7% 309/555 were R-ISS stage II and 26.8% (149/555) patients were R-ISS III. Median overall survival was not reached for stage I, 3.9 years for stage II and 2.5 years for stage III. The differences were statistically significant (p 〈 0.001, log-rank test). Median time to progression was 3.3 years for stage I, 1.9 years for stage II and 1.3 years for stage III. The differences were statistically significant (p 〈 0.001, log-rank test). Stage I versus II showed HR (95% CI): 2.84 (1.66-4.87), p 〈 0.001 and stage I versus III HR (95% CI): 5.20 (2.99-9.03), p 〈 0.001 for overall survival and HR (95% CI): 2.02 (1.37-2.96), p 〈 0.001 and (95% CI): 2.49 (1.64-3.77), p 〈 0.001 for time to progression. Similar survival pattern can be seen in a subgroup of patients treated with autologous stem cell transplantation, without autologous stem cell transplantation and the system provides valuable information even in a subgroup of patients who were never treated with novel agents. Figure 1 shows overall survival and figure 2 time to progression of the cohort. Conclusion: Revised ISS provides valuable information about the long term prognosis in a mixed cohort of real life multiple myeloma patients. This system enables to estimate the prognostic category of each specific patient in a horizon of several years ahead. Supported by PRVOUK P37. Table 1 Table 1. Figure 1 Overall survival for R-ISS stages Figure 1. Overall survival for R-ISS stages Figure 2 Time to progression for R-ISS stages Figure 2. Time to progression for R-ISS stages Disclosures Spicka: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Millenium: Honoraria. Hájek:Janssen: Honoraria; Celgene: Consultancy, Research Funding; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy.

Abstract: In this study, the content of As, Cd and Hg in fruiting bodies was determined. These three elements were determined in 94 Macrolepiota procera (Scop.) Singer samples (separately for caps and stems) and their corresponding soils/substrates collected from 8 different localities in Slovakia. Arsenic and cadmium were analyzed by Optical Emission Spectrometry with Inductively Coupled Plasma (OES-ICP), and mercury by Advanced Mercury Analyzer (AMA-254). In the soil/substrate As content varied from ND (not detected) to 11.9, Cd from 0.66 to 22.9 and Hg from 0.02 to 0.28 mg kg-1 DW (dry weight), respectively. In fruiting body stems arsenic content varied from ND to 4.77, cadmium from ND to 5.96 and mercury from 0.03 to 2.83 mg kg-1 DW. In the caps, As content varied from ND to 13.0, Cd from ND to 19.8 and Hg from 0.04 to 4.00 mg kg-1 DW. After comparing obtained results with the EU limits, for As in mushrooms 6.6% (cap) of analyzed samples exceeded the limit value, while for Cd, 4.7% (cap), 2.0% (stem) of analyzed samples exceeded the limit value. Regarding the background values in the soils/substrates of selected elements in Slovakia only Cd exceeded the limits (though almost 82% of samples). Regarding Hg content, all analyzed samples (fruiting bodies and soils/substrates) did not exceed the limit value. The selected monitored localities in Slovakia have been contaminated with trace elements. Some of the analyzed mushroom samples exceeded EU limits, and as such, they can pose a risk to human health.

Abstract: BACKGROUND: The European Commission has granted conditional approval to daratumumab (DARA) as monotherapy in adult patients (pts) with relapsed or refractory multiple myeloma (MM) whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) and who have demonstrated disease progression on the last therapy. DARA was approved under an accelerated assessment based on single-arm phase 2 studies. Outcomes in these heavily pretreated pts in a real-world (RW) setting can provide evidence on the relative treatment efficacy of DARA versus physician's choice (PC). AIMS: To perform an adjusted comparison of overall survival (OS) and progression-free survival (PFS) for DARA monotherapy versus PC, as observed in a RW historical cohort of heavily pretreated and highly refractory MM pts from the Czech Republic using pt-level data. METHODS: Using RW longitudinal pt chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, pts with ≥2 prior lines of therapy previously exposed to both a PI and an IMiD were identified. Pt-level data from the RMG were pooled from pivotal DARA monotherapy studies (pts treated with DARA 16 mg/kg). Pts in the RMG could contribute information to the analysis for multiple lines of therapy, with baseline defined as the date of initiation of the actual treatment line. For the definition of PFS, missing data for the date of disease progression for pts in the RMG who initiated subsequent therapy were replaced by the conservative proxy of the date of initiation of the next treatment. OS and PFS were analysed using a Kaplan-Meier analysis. To adjust for confounding variables, a multivariate Cox proportional hazards regression was developed that included age, gender, beta-2 microglobulin levels (β2M : & lt;3.5/3.5-5.5/ & gt;5.5 g/L), albumin levels ( & lt;3.5/≥3.5 g/L), line of therapy (3-13), prior exposure to pomalidomide/carfilzomib, refractory status (none/double/triple/quadruple), andincidence of thrombocytopenia (defined as platelet counts & lt;150.000 per µL) as covariates. Predicted PFS and OS curves for the RMG cohort were derived from the multivariate model. RESULTS: From the RMG database, we identified 971 treatment lines in 463 pts previously exposed to both a PI and an IMID (n=206 in third line, n=256 in fourth line, n=203 in fifth line, n=307 in ≥sixth line). The dates of treatment initiation for the RMG pts ranged from March 2006 to March 2015. The most frequent treatment regimens were lenalidomide (33.4%), chemotherapy (18.1%), bortezomib (13.6%), thalidomide (8.0%), and bortezomib+thalidomide (5.3%). The number of pts treated with carfilzomib (2.5%) and pomalidomide (2.4%) was limited. DARA-treated pts (N=148) differed from the RMG cohort in median age (64 vs 62 years), median prior lines of therapy (5 vs 4), prior exposure to carfilzomib (41.2% vs 0.3%) and pomalidomide (55.4% vs 0.6%), thrombocytopenia incidence (46.9% vs 18.0%), and ≥triple refractory status (64.2% vs 5.3%). Median observed PFS and OS for DARA versus PC were 4.0 and 5.6 months, respectively, for PFS and 20.1 and 11.9 months, respectively, for OS. Older age, male sex, low albumin levels, high β2M levels, thrombocytopenia incidence, and double/triple/quadruple refractory status were all independent, statistically significant risk factors for mortality. Albumin levels, β2M levels, thrombocytopenia incidence, and refractory status were also predictive of PFS. The adjusted hazard ratio (95% confidence interval) for OS and PFS for DARA versus PC was 0.35 (0.22-0.56) and 0.79 (0.56-1.12), respectively. Figure 1 represents the predicted survival curves for the RMG cohort that were derived from the multivariate model, comparing observed PFS/OS versus predicted with DARA treatment. CONCLUSIONS: This adjusted treatment comparison suggests a significant improvement in OS and a numerical improvement in PFS for DARA compared to RW historical control data in heavily pretreated/highly refractory MM pts. The lower PFS benefit estimate for DARA compared to OS may be partly explained by limitations in the availability and comparability of data regarding progressive disease in the RMG cohort compared to clinical trial data. Adjusted comparisons between trial data and historical cohorts can provide useful insights to clinicians and reimbursement decision makers on relative treatment efficacies in the absence of head-to-head comparison studies for DARA monotherapy. Disclosures Hájek: Amgen: Honoraria, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Spicka:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millenium: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Gatopoulou:Janssen Health Economics & Market Access EMEA: Employment. Vesela:Janssen Cilag s.r.o., Czech Republic: Employment. Diels:Johnson & Johnson: Employment, Equity Ownership. Besson:Janssen: Employment. Ito:Janssen: Employment, Equity Ownership.