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Human Cytomegalovirus Infection in Patients after Allogeneic Hematopoietic Stem Cell Transplantation
Vejražková, Eva ; Žák, Pavel (advisor) ; Faber, Edgar (referee) ; Lysák, Daniel (referee)
Eva Vejražková: Human Cytomegalovirus Infection in Patients after Allogeneic Hematopoietic Stem Cell Transplantation - Summary Introduction: Specific anti-cytomegalovirus (CMV) treatment reduces CMV-related morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT) but carries a risk of viral resistance. The viral resistance after HSCT treatment is still a relatively unexplored phenomenon. The aim of the study was to determine the incidence of CMV infection in patients within one year after HSCT in our centre. The goal was also to analyse CMV infection data, incidence of graft-versus-host disease and other clinical endpoints by comparing two patients' cohorts that were administered two different Thymoglobuline Genzyme (TG) doses as part of the HSCT conditioning regimen. Incidence of treatment failure cases and viral CMV drug resistance were also to be determined. Two methods of sequence analysis (Sanger and Next-Generation Sequencing, NGS) were compared in cases of proven viral resistance. Patients cohort and methods: The study included 101 adult patients after allogeneic HSCT for haematological diseases treated between July 2012 and December 2014 at the Hradec Kralove University Hospital, Czech Republic. CMV DNAemia was determined by quantitative real-time PCR, the...
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The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneie hematopoietic stem cell transplantation
Karas, Michal ; Holubec, Luboš (advisor) ; Faber, Edgar (referee) ; Žák, Pavel (referee)
In this thesis entitled " The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneic hematopoietic stem cell transplantation " the author deals with the following issues: 1. In the literature overview: the author characterizes the epidemiology, patogenesis, diagnostics, prognosis and treatment of acute myeloid leukemia, focusing on evaluation of different prognostic markers in relation to the treatment of acute myeloid leukemia mainly using allogeneic hematopoietic stem cell transplantation. 1. The methodological section characterizes the following: a) Groups of patients and methods of clinical evaluation in: Detailed characteristics of 60 patients with acute myeloid leukemia with normal karyotype and NPM1 gene mutations in complete remission who underwent allogeneic hematopoietic stem cell transplantation on Haematology and oncology department of University Hospital Pilsen in the years 2005-2014. The evaluation of other parameters of the underlying disease, and a detailed description of transplant procedure (donor selection, the type of pre-transplantation preparation etc.) is also part of characteristics. b) The timing and method of sampling for evaluation of the level of minimal residual disease before transplantation. Description of the method for...
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Pathophysiologic aspects of myelodysplastics syndromes in relation to the effect of targeted imunomodulation and demetylation therapy
Jonášová, Anna ; Stopka, Tomáš (advisor) ; Maisnar, Vladimír (referee) ; Faber, Edgar (referee)
Myelodysplastic syndromes (MDS) represent a group of clonal stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenia, morphological dysplasia and the risk of transformation to acute myeloid leukemia (AML). MDS belongs to one of the most common hematological diseases in patients over 60 years old. MDS incidence is still increasing. Appropriate therapy of MDS remains challenging. There is no curative approach besides peripheral stem cells transplantation, which is regretfully appropriate only for a small group of patients due to a higher median age of the MDS population. This is why the search for therapeutic alternatives remains paramount. MDS treatment was rather frustrating until the recent introduction of two new therapeutic approaches: immunomodulation therapy with lenalidomide and epigenetic or demethylating therapy with 5-azacytidine. Both new drugs have significantly higher effect than standard therapy. However, the precise mechanism of this effect remains unknown. As a result, we decided to initiate several research projects while introducing this promising treatment to our patients. Our aim is to investigate the mechanism of both agents in relation to disease pathogenesis by examining changes of certain occurrences and factors prior to and during the course of...
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Human Cytomegalovirus Infection in Patients after Allogeneic Hematopoietic Stem Cell Transplantation
Vejražková, Eva ; Žák, Pavel (advisor) ; Faber, Edgar (referee) ; Lysák, Daniel (referee)
Eva Vejražková: Human Cytomegalovirus Infection in Patients after Allogeneic Hematopoietic Stem Cell Transplantation - Summary Introduction: Specific anti-cytomegalovirus (CMV) treatment reduces CMV-related morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT) but carries a risk of viral resistance. The viral resistance after HSCT treatment is still a relatively unexplored phenomenon. The aim of the study was to determine the incidence of CMV infection in patients within one year after HSCT in our centre. The goal was also to analyse CMV infection data, incidence of graft-versus-host disease and other clinical endpoints by comparing two patients' cohorts that were administered two different Thymoglobuline Genzyme (TG) doses as part of the HSCT conditioning regimen. Incidence of treatment failure cases and viral CMV drug resistance were also to be determined. Two methods of sequence analysis (Sanger and Next-Generation Sequencing, NGS) were compared in cases of proven viral resistance. Patients cohort and methods: The study included 101 adult patients after allogeneic HSCT for haematological diseases treated between July 2012 and December 2014 at the Hradec Kralove University Hospital, Czech Republic. CMV DNAemia was determined by quantitative real-time PCR, the...
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Rheohemapheresis (Clinical Importance of Rheological, Technical and Further Hemapheretic Indicators of Effectivity; Side-effects and Economy)
Lánská, Miriam ; Bláha, Milan (advisor) ; Gašová, Zdenka (referee) ; Faber, Edgar (referee)
SUMARY RHEOHEMAPHERESIS - Clinical Importance of Rheological, Technical and Further Hemapheretic Indicators of Effectivity , Side-effects and Economy INTRODUCTION: (Haema)rheopheresis combines the possibilities of haemapheresis (a therapeutic method that is focused on the separation of blood components) and medical rheology (a field of science studying blood fluidity and applying the results of this research to clinical practice in pathological impairments, mainly in the area of microcirculation). The rationale of the effect of rheopheresis (RF): the procedures simultaneously eliminate the exactly defined spectrum of rheologically relevant high-molecular proteins. An immediate pulse reduction of plasma viscosity and viscosity of full blood occurs, which can lead to subsequent permanent "recovery" of the microcirculation with the use of a series of procedures and significantly change the natural course of chronic therapy. RF has been tested in several diseases. This study involves the use of rheopheresis in the dry form of age-related macular degeneration (AMD) and sudden idiopathic sensorineural hearing loss - SISHL. The research was aimed at the optimisation of own modification of rheopheresis, effectivity of procedures, search for the markers of immediate efficacy and prognosis, evaluation of safety and...
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Optimizing treatment options for patients with chronic myeloid leukemia
Bělohlávková, Petra ; Žák, Pavel (advisor) ; Faber, Edgar (referee) ; Ráčil, Zdeněk (referee)
Introduction Patients with chronic myeloid leukemia (CML) are usually treated with imatinib 400 mg/day. Despite excellent therapeutic response to imatinib, 20 - 30 % patients are resistant to this treatment. Several molecular mechanisms leading to imatinib resistance have been proposed (amplification and overexpression of the BCR/ABL1 gene, point mutations). It has been suggested that one of the reasons for the varied response to imatinib may be due to inter- individual differences in imatinib metabolism. Objective The primary goal was to find new biological parameters which could clarify the cases of unexplained imatinib failure. In our study we analyzed the influence of polymorphism in seven genes linked to the pharmakokinetics of imatinib: CYP3A5*3 (rs 776746), CYP3A4*1 (rs 2740574), CYP2C9*3 (rs 1057910), SLCO1 (rs 683369), ABCB1 (rs1045642, rs 1128503), ABCG2 (rs 2231142) and ABCC2 (rs 717620). We evaluated the association of these polymorphisms in optimal response and plasma levels of imatinib. The secondary objective was to evaluate whether the standard dose of imatinib 400 mg/daily leads to achieving optimal therapeutic response and whether this dose induces a sufficient plasma levels of imatinib. Methods and results We analyzed 112 patients with CML. Our cohort included 53 men (47 %) and 59...
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Pathophysiologic aspects of myelodysplastics syndromes in relation to the effect of targeted imunomodulation and demetylation therapy
Jonášová, Anna ; Stopka, Tomáš (advisor) ; Maisnar, Vladimír (referee) ; Faber, Edgar (referee)
Myelodysplastic syndromes (MDS) represent a group of clonal stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenia, morphological dysplasia and the risk of transformation to acute myeloid leukemia (AML). MDS belongs to one of the most common hematological diseases in patients over 60 years old. MDS incidence is still increasing. Appropriate therapy of MDS remains challenging. There is no curative approach besides peripheral stem cells transplantation, which is regretfully appropriate only for a small group of patients due to a higher median age of the MDS population. This is why the search for therapeutic alternatives remains paramount. MDS treatment was rather frustrating until the recent introduction of two new therapeutic approaches: immunomodulation therapy with lenalidomide and epigenetic or demethylating therapy with 5-azacytidine. Both new drugs have significantly higher effect than standard therapy. However, the precise mechanism of this effect remains unknown. As a result, we decided to initiate several research projects while introducing this promising treatment to our patients. Our aim is to investigate the mechanism of both agents in relation to disease pathogenesis by examining changes of certain occurrences and factors prior to and during the course of...
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The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneie hematopoietic stem cell transplantation
Karas, Michal ; Holubec, Luboš (advisor) ; Faber, Edgar (referee) ; Žák, Pavel (referee)
In this thesis entitled " The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneic hematopoietic stem cell transplantation " the author deals with the following issues: 1. In the literature overview: the author characterizes the epidemiology, patogenesis, diagnostics, prognosis and treatment of acute myeloid leukemia, focusing on evaluation of different prognostic markers in relation to the treatment of acute myeloid leukemia mainly using allogeneic hematopoietic stem cell transplantation. 1. The methodological section characterizes the following: a) Groups of patients and methods of clinical evaluation in: Detailed characteristics of 60 patients with acute myeloid leukemia with normal karyotype and NPM1 gene mutations in complete remission who underwent allogeneic hematopoietic stem cell transplantation on Haematology and oncology department of University Hospital Pilsen in the years 2005-2014. The evaluation of other parameters of the underlying disease, and a detailed description of transplant procedure (donor selection, the type of pre-transplantation preparation etc.) is also part of characteristics. b) The timing and method of sampling for evaluation of the level of minimal residual disease before transplantation. Description of the method for...
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