Showing papers by "Jana Markova published in 2022"
TL;DR: In this article , the authors present the results of a case study that was prepared as a basis for decision-making processes in the context of the impacts of global climate change on urban forests.
Abstract: The paper presents the results of a case study that was prepared as a basis for decision-making processes in the context of the impacts of global climate change. The article is focused on a very important part of the urban environment, namely urban forests. When taking planning measures in periurban forests, two realities must always be addressed, i.e., adaptation measures to mitigate the effects of climate change on the forest complex in question and its use to mitigate the effects of climate change in its surroundings must both be considered. It is a well-known fact that forest communities (of any kind) are on the one hand affected by the impacts of climate change, but on the other hand are able to mitigate its effects on their surroundings. The case study was of land near the town of Mladá Boleslav. The aim was to analyse the hydrological regime of the Štěpánka Forest Park, nicknamed “the lungs of Mladá Boleslav”. Modelling of the runoff coefficient was made for the whole park area, as well as for the part on the left bank of the Klenice River (forested part). The runoff conditions of the site and their subparameters are addressed in the study by comparing the current state with the modelled state after deforestation of the site, e.g., due to drought. As far as the spatial layout of the forest is concerned, it is absolutely essential to maintain an integrated stand on the site with a lower stem cover (fewer individuals per plot) and a lower regeneration period. These aspects of a growing matrix forest stand will ensure its sustainability, in particular the sustainable water management of the trees in the context of lower water reserves in the rhizosphere and the greater ability of younger individuals to adapt to changes in site conditions (replacement of stress-resistant types by resilient types).
2 citations
TL;DR: In the AETHERA trial, BV 1.8 mg/kg i.v. was administered to 39 patients with relapsed/refractory classic Hodgkin lymphoma (cHL) in the Czech Republic as mentioned in this paper .
Abstract: Figure 1: Progression-free survival figure, N=39 pts Introduction: Consolidation therapy with brentuximab vedotin (BV) following autologous stem cell transplantation (ASCT) has demonstrated improved progression-free survival (PFS) in high-risk patients (pts) with relapsed/refractory classic Hodgkin lymphoma (cHL) in the AETHERA trial. We have analysed data from seven centres of intensive haematological care in the Czech Republic between January 2015 and December 2021 based on real-life experience with the treatment. The primary goals included basic statistical decription, assessment of the PFS and toxicity of the treatment. Patients and Methods: All of the pts were treated with high-dose chemotherapy and ASCT in the first relapse, all had at least one of the risk factors as per AETHERA and no previous treatment with BV. We have analysed 39 pts treated with BV 1.8 mg/kg i.v. every 3 weeks for a maximum of 16 cycles. Results: Median age was 37 years (range 19–65) at the time of the first dose of BV. Nearly 80% of pts were initially treated as advanced stage cHL and eBEACOPP was administered in 59% of pts in the frontline setting. Primary refractory or early relapsed (within 12 months after the frontline therapy) cHL pts represented 69% of the analysed cohort. Two different salvage regimens were administered in 30.8% and failure to achieve a complete response (CR) after salvage chemotherapies prior ASCT was seen in 64% of pts. The median number of BV administered was 8 (1–16), with 16 completed cycles in 20.5% pts. Main reasons for early discontinuation were neuropathy and relapsed or progressive disease, both in 15.4%. Overall, 82% of pts achieved CR during the treatment. With a median follow-up 28 months the 2-year PFS was 66.2% (95% CI 0.52–0.85) and the 2-year overall survival was 95% (95% CI 0.82–1.00). Two pts died, one of progressive lymphoma and one of severe bacterial infection. Peripheral sensory neuropathy occurred in 38.5% (grade 3–4 in 10.3%), neutropenia in 28.2% (grade 3–4 in 17.9%) and respiratory infections in 28.5% (grade 3–4 in 2.6%). Discussion: Despite some differences in the analysed groups, our results are comparable with a few real-world data published lately and support the notion that BV consolidation improves PFS in patients with at least one risk factor for subsequent relapse of cHL and has a feasible and manageable toxicity. Supported by following grants MH CZ – DRO (FNOl, 00098892) AZV NU22-03-00182
1 citations
TL;DR: The results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape, and the predicted response to standard therapy of patients in specific AML subgroups should be targeted to improve AML treatment.
Abstract: ABSTRACT The immune system is important for elimination of residual leukemic cells during acute myeloid leukemia (AML) therapy. Anti-leukemia immune response can be inhibited by various mechanisms leading to immune evasion and disease relapse. Selected markers of immune escape were analyzed on AML cells from leukapheresis at diagnosis (N = 53). Hierarchical clustering of AML immunophenotypes yielded distinct genetic clusters. In the absence of DNMT3A mutation, NPM1 mutation was associated with decreased HLA expression and low levels of other markers (CLIP, PD-L1, TIM-3). Analysis of an independent cohort confirmed decreased levels of HLA transcripts in patients with NPM1 mutation. Samples with combined NPM1 and DNMT3A mutations had high CLIP surface amount suggesting reduced antigen presentation. TIM-3 transcript correlated not only with TIM-3 surface protein but also with CLIP and PD-L1. In our cohort, high levels of TIM-3/PD-L1/CLIP were associated with lower survival. Our results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape. Cellular pathways regulating resistance to the immune system might contribute to the predicted response to standard therapy of patients in specific AML subgroups and should be targeted to improve AML treatment.
1 citations
TL;DR: In this paper , the fertility of 119 young female patients with initial diagnosis of Hodgkin lymphoma (HL) in advanced stages treated with eBEA was analyzed and showed that 38% of young fertile women with advanced stages of HL are able to deliver babies.
Abstract: Background: BEACOPP escalated (eBEA) includes alkylating agents and its gonadal toxicity has been reported in prospective and retrospective studies. This retrospective study analyzed fertility of 119 young female patients (pts) with initial diagnosis of Hodgkin lymphoma (HL) in advanced stages treated with eBEA. Patients and Methods: Overall 128 women aged 18–34 years (median age at diagnosis was 27 years) were treated with eBEA between 1997 and 2020. Median follow-up since the beginning of the treatment was 12.4 years. Overall 57 pts (48%) received 8 cycles of eBEA, 46 pts (39%) were treated wit 6 cycles and 16 pts (13%) received 4 cycles of eBEA. Additional radiotherapy was indicated in 36 pts (30%). Gonadotropin-releasing hormone-analogue Gosereline acetat received 68 pts (57%) and 51(43%) pts used oral contraceptives during chemotherapy to prevent gonadal toxicity. Median follow-up after the end of treatment was 12 years. Results: Out of 119 women 45 (38%) delivered 61 babies including 18 (40%) women with 2 deliveries after treatment with eBEA. Number of all delivered healthy babies was 59 (one baby was born with small cleft lip, other with mild renal malformation). Two pregnancies were terminated prematurely (week 20 and 22) due to congenital malformations: monozomy 45, X0 Turner syndrome and serious cleft lip). All pregnancies were spontaneous except of 6 women that underwent in vitro fertilisation (IVF) Median time from the end of terapy until the delivery of the first baby was 66 months (range 18-169m). 40 children (65%) were born in the group of pts aged 18–24 years, 16 (26%) in the group of 25–29 years and only 5 (9%) in the group of 30–34 years. Conclusion: Our data indicate that even after eBEA 38% of young fertile women in advanced stages of HL are able to deliver babies and protection of fertility should be offered to them. Implementation of new strategies with reduction of chemotherapy cycles based on PET may further contribute to fertility preservation.
TL;DR: The NUP98::NSD1 fusion gene was found to occur most frequently in children (16%) and young (2%) patients, very rarely in adult patients as discussed by the authors .
Abstract: Background: The NUP98::NSD1 fusion, a product of the cryptic translocation t(5;11)(q35;p15.5), is a recurrent genetic change in cytogenetically normal patients with AML. It occurs most frequently in children (16%) and young (2%) AML patients, very rarely in adult patients. The coexistence of internal tandem duplication of FLT3 gene (FLT3::ITD) found in more than 70% of NUP98::NSD1 positive patients is always associated with a poor prognosis and results in high frequency of induction failure. Aims: The aim of this study was to determine the incidence of the NUP98::NSD1 fusion gene in adults with AML and NUP98 rearrangement. Methods: We examined the bone marrow cells of 268 newly diagnosed AML patients using conventional karyotyping in combination with FISH (Abbott, MetaSystems) and mFISH/mBAND (MetaSystems). We used RT-PCR followed by direct sequencing to detect fusion genes. We processed the PCR product by ExoSAP-IT and directly sequenced on ABI Prism 310 genetic analyzer using the Big Dye Terminator kit v. 3.1. Results: In nine out of 268 cases we identified rearrangement of the 11p13-15 region. We confirmed t(5;11)(q35;p15.5) with NUP98::NSD1 gene fusion in four of them (4/268; 1.5%). Sequence analyses proved the NUP98-NSD1 transcript, arising from fusion of NUP98 exon 12 with exon 6 in NSD1 gene, in all four patients (2M/2F; FAB M4/M5b; age 42, 54, 64 and 64 years). FLT3::ITD mutation was detected in all of them. Specific primers and a probe have been designed to monitor minimal residual disease during therapeutic treatment of the patients. Out of 4 patients, two died (median OS 9 months) and two patients are alive (4 and 1 year after allogenic bone marrow transplantation). Summary/Conclusion: Our study demonstrated the occurrence of t(5;11)(q35;p15.5) with NUP98::NSD1 gene fusion also in adults over 60 years of age. We confirmed the NUP98::NSD1 fusion gene in 1.5% adults AML patients. With respect to the poor prognosis of the patients with NUP98::NSD1 fusion gene, we suggest pre-screening of NUP98 gene rearrangement using FISH in cytogenetically normal AML patients with confirmed FLT3::ITD mutation. Supported by MH CZ-DRO-VFN64165, DRO-UHKT00023736.
TL;DR: In this article , the impact of anticipated changes in European climate could affect the assessment of design weather parameters, including the partial factor design approach for structures according to Eurocodes, based on current knowledge concerning projection models of future climate in Europe.
Abstract: The climatic data on which the current generation of the Eurocodes are based are mostly about 20 years old, with some exceptions of recent updates at a national level. The second generation of the Eurocodes for structural design is expected to be nationally implemented within next few years and operational National Annexes should be subsequently developed and the climatic maps revised. Some models for extreme climate actions are still missing within Eurocodes including wind action effects due to non-synoptic storms, which are common in most of the world and are of increasing importance in Europe.The aim of this contribution is to analyse how the impact of anticipated changes in European climate could affect the assessment of design weather parameters, including the partial factor design approach for structures according to Eurocodes, based on current knowledge concerning projectionmodels of future climate in Europe.
TL;DR: In this paper , the authors compared PET2-adapted approach with 2 + 2 chemotherapy followed by 30 Gy of involved-node radiotherapy (INRT) regardless of interim PET in patients with early unfavorable cHL assessed according to the GHSG risk factors.
Abstract: Background: PET2-adapted approach after 2 cycles of ABVD reduced treatment intensity in the majority of patients with early stages of classical Hodgkin lymphoma (cHL) according to EORTC H10 trial. GHSG HD17 enabled omission of radiotherapy in PET4-negative early unfavorable HL treated with 2 cycles of BEACOPP escalated and 2 cycles of ABVD (2 + 2 chemotherapy). We compared PET2-adapted approach with 2 + 2 chemotherapy followed by 30 Gy of involved-node radiotherapy (INRT) regardless of interim PET in patients with early unfavorable cHL assessed according to the GHSG risk factors. Methods: Overall, 224 patients with early unfavorable cHL (aged 18–60 years) prospectively observed in the Czech Hodgkin Lymphoma Study Group Registry between 2003–2021 were analyzed. Patients in clinical stage IIB with massive mediastinal tumor and/or with extranodal disease were excluded. Overall, 194 patients received 2 + 2+INRT chemotherapy and 30 patients were treated with PET2-adapted approach: 29 PET2-negative patients received 4 cycles of ABVD and 30 Gy of INRT and one PET2-positive patient was treated with 2 cycles of ABVD plus 2 cycles of BEACOPP escalated and 30 Gy INRT. Results: Median age at the time of cHL diagnosis was 32 (range 18–59) years. Median follow-up was longer in the 2 + 2+INRT group (98.9, range 6.2–211.7) months compared to the PET2-adapted approach (30.8, range 9.8–90.4) months. The 2-year progression-free survival and 2-year overall survival did not differ between two groups (99.5% [95% CI 98.5%–100%]) and 100% [95% CI 100%–100%]), respectively. The rate of patients with neutropenia grade 3 and anemia grade 3 did not differ significantly between both groups (p=0.09 and p=0.60, respectively). Thrombocytopenia was more frequent in the 2 + 2+INRT group (p0.001). Grade 3 non-hematological toxicity occurred in 3 patients in the 2 + 2+INRT group (2 infections, 1 deep vein thrombosis). Conclusion: This retrospective analysis indicates that there is no superiority in progression-free survival and overall survival when comparing 2 + 2 chemotherapy and INRT to PET2-adapted approach. The toxicity is higher in the 2 + 2+INRT group. This work was supported by the following grants AZV NU22-03–00182 from the Ministry of Health of the Czech Republic and Cooperatio Program awarded by the Charles University in Prague in the Czech Republic.