II. Interni Klinika Oddeleni Klinicke Hematologie

Hradec Králové, Czech Republic

II. Interni Klinika Oddeleni Klinicke Hematologie

Hradec Králové, Czech Republic
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St'astny M.,Bristol Myers Squibb | Machova Polakova K.,Ustav Hematologie a Krevni Transfuze Prague | Klamova H.,Ustav Hematologie a Krevni Transfuze Prague | Zackova D.,Interni Hematoonkologicka Klinika a Masarykovy Univerzity Brno | And 4 more authors.
Transfuze a Hematologie Dnes | Year: 2010

Chronic myeloid leukemia (CML) becomes a disease, treatment of which represents typical example of tailored therapy. Despite the fact that first line therapy of CML using imatinib revolutionized the treatment of this disease, it became clear that during 5 years 25-35 % of the patients require change in the therapy due to the development of imatinib resistance or intolerance. The most frequent mechanism responsible for imatinib resistance is development of mutation in BCR-ABL kinase domain. Mutations cause different level of imatinib resistance and while some of them can be overcome by increased dose of imatinib (M351T), others seem to be resistant to nilotinib (P-loop mutations, F359C/V) and others are more resistant to dasatinib (F317L/V a V299L). This review is focused only to clinically most important mutations occurring in 15 amino-acid substitutions, which account for more than 85 % of all BCR-ABL mutations. It has been shown recently that advances in molecular methods enable to better understand disease itself, weigh the benefit to risk ratio of the therapy, individualize therapeutic approach and eventually adjust CML therapy earlier in order to minimize the risk of CML progression to advanced phases.

Klincova M.,Interni hematoonkologicka klinika FN a LF MU Brno | Mikulasova A.,Masaryk University | Kovarova L.,Laboratory experimentalni a bunecne imunoterapie FN | Sandecka V.,Interni hematoonkologicka klinika FN a LF MU Brno | And 10 more authors.
Onkologie | Year: 2011

Monoclonal gammopathy of undeterminated significance (MGUS) and asymptomatic form of myeloma are associated with a long-term risk of progression to active disease symptomatic multiple myeloma or related malignancy. As far as the malignant transformation of MGUS is concerned, size and type of the serum monoclonal immunoglobulin (monoclonal protein, M-protein, M-Ig), serum kappa and lambda free light chain ratio, number of clonal plasma cells in bone marrow, number of clonal plasma cells in peripheral blood, immunophenotype of plasma cells, and another factors seem to play a predictive role.

Maisnar V.,II. Interni Klinika Oddeleni Klinicke Hematologie | Klimes D.,Institute Biostatistiky a Analyz | Pelcova J.,Interni Hemato Onkologicka Klinika | Hajek R.,Interni Hemato Onkologicka Klinika
Klinicka Biochemie a Metabolismus | Year: 2011

Registry of monoclonal gammopathies is currently one of the main Czech Myeloma Group projects. The purpose of this project is the prospective data analysis of monoclonal gammopathies patients in the region of the middle and also the east Europe including incidence of diseases, therapeutical modalities used, the treatment results and the most frequent averse events of therapy. It is ambitious project which should be accompanied with better care of this type of patients in the future.

Radocha J.,II. Interni Klinika Oddeleni Klinicke Hematologie | Klincova M.,Interni Hematoonkologicka Klinika | Maisnar V.,II. Interni Klinika Oddeleni Klinicke Hematologie | Sandecka V.,Interni Hematoonkologicka Klinika | And 8 more authors.
Klinicka Biochemie a Metabolismus | Year: 2012

Our project was focused on verifying the usefulness of free light chain (FLC) analysis as the new marker for evaluation of the activity of monoclonal gammopathies. Formulated goals of this project represented the most likely beneficial indications for FLC use in clinical practice. We collaborated with Registry of Monoclonal Gammopathies database of Czech Republic and analyzed 1439 patients with monoclonal gammopathies. We were able to confirm validity of the prognostic model of MGUS stratification originally developed by Mayo Clinic. Moreover several other independent prognostic factors not included in the mentioned model have been identified, which we plan to include in the further analysis and development of more detailed prognostic model. Normalization of FLC ratio was not connected to statistically significant prolongation of complete remission duration, however trend towards it was observed.

Plisek S.,Klinika Infekcnich Nemoci | Kosina P.,Klinika Infekcnich Nemoci | Chlibek R.,Katedra Epidemiologie | Prasil P.,Klinika Infekcnich Nemoci | And 10 more authors.
Vakcinologie | Year: 2010

In total 128 cases of pandemic A (H1N1) 2009 influenza were diagnosed at the University Hospital in Hradec Králové over the follow-up period of July 2009 - January 2010. An analysis of a group of patients focusing on the age structure, epidemiologic case history, clinical symptoms and complications, the incidence of intercurrent chronic diseases, and also the effect and length of antiviral therapy including secondary therapy was carried out. The first group of cases were imported diseases which finally comprised 16% of the whole group (20 patients). The most affected group were the middle-age people (average age 30) with a slight prevalence of females (55.5%). The median length of hospitalization of 86 persons (67.2%) in the follow-up group was 6 days. A typical clinical picture included fever (90 %), cough, headache, articulation pain and vomiting. Complications occurred in 75 % of hospitalized patients and a predominant complication was acute interstitial pneumonia. Mortality rate in the hospitalized patients exceeded 9 % (8 patients). The study of all cases proved a risk factor especially in patients with hemato-oncological and chronic pulmonary diseases, hereafter gravidity and obesity. A specific antiviral therapy (oseltamivir) was applied in 57 % of patients, the median length of therapy was 5 days. Artificial pulmonary ventilation was introduced in 20 patients (15.6%).

Pika T.,III. Interni Klinika Nefrologicka | Lochman P.,Oddeleni Klinicke Biochemie | Klincova M.,Laborator Experimentalni Hematologie A Bunecne Imunoterapie | Maisnar V.,II. Interni Klinika Oddeleni Klinicke Hematologie | And 5 more authors.
Klinicka Biochemie a Metabolismus | Year: 2012

Introduction: Monoclonal gammopathy of undetermined significance (MGUS) indicates an asymptomatic and potentially malignant state characterised by benign clonal proliferation of plasma cells secerning (discharging) monoclonal immunoglobulin (MIG, M-protein) detectable in serum and/or urine in the absence of malignant lymphocyte proliferation. It has been observed that in some patients, MGUS transforms into one of the malignant forms of monoclonal gammopathy. The wellknown factors determining the risk degree of progression include in particular the quantity, M-protein type and the ratio of immunoglobulin free light chains (FLC) allowing the efficient stratification of MGUS patients. In addition, several authors consider the present suppression of polyclonal immunoglobulin levels to be a potential factor of progression. Aim: The study aimed at conducting a pilot analysis of levels of immunoglobulin heavy/light chains pairs (HLC) in a group of MGUS patients and at comparing the results with the M-protein levels detected by gel electrophoresis. Furthermore, the polyclonal immunoglobulin levels and the levels of HLC alternative pairs were to be compared with a view to verify the degree of immune paresis depending on the MGUS risk degree. Methods: The analysed set comprised 148 serum samples of MGUS patients (102 IgG, 28 IgA, 18 IgM type) who were stratified into 4 risk groups (low, low-intermediate, high-intermediate, and high risk of transformation) according to the levels, M-protein type and FLC index values. FLC levels, polyclonal immunoglobulin levels, and HLC levels were determined by means of the SPA Plus turbidimeter platform. In the statistical analysis, Spearmans rank correlation and Mann-Whitney U Test with Bonferroni correction were applied. Results: When comparing the HLC levels, the IgG MGUS group revealed strong correlation with M-protein levels both in the case of IgGκ (r = 0.698, p = < 0.0001), and in the case of IgGλ (r = 0.847, p = < 0.0001), the summation of both pairs of the IgG isotype correlated considerably with the total levels of IgG in serum (r = 0.893, p = < 0.0001). Similar results were acquired in MGUS with the IgA isotype of MIG. In case of the IgAκ isotype pair, medium-strong correlation with M-protein levels was detected (r = 0.601, p = 0.018), and strong correlation in case of the IgAλ (r = 0.733, p = 0.004), whereas the summation of both HLC pairs showed very strong correlation with levels of the total IgA (r = 0.941, p = < 0.0001). Moreover, analyses of IgM type patients revealed very strong correlation of IgMκ levels (r = 0.904, p = 0.001) or IgMλ (r = 0.783, p = 0.013) and M-protein levels. Again, the strongest correlation was found between the summation of both isotype pairs and the total levels of IgM immunoglobulin in serum (r = 0.967, p = < 0.0001). Comparison of the suppression degree of polyclonal immunoglobulin levels in individual risk classes in the IgG MGUS group brought significantly higher levels of IgA immunoglobulin in patients with low or low-intermediate risk as opposed to the group with high-intermediate risk (p = 0.0001 and p = 0.047 respectively). When analysing the MGUS group with IgA isotype, notably higher levels of IgM immunoglobulin were evident in the group with low-intermediate risk than in patients with high-intermediate or high risk (p = 0.035 and p = 0.017 respectively). In addition, the levels of alternative isotype pairs were compared among the individual risk groups of the IgG MGUS group. Patients with dominant IgGκ secretion showed significantly higher levels of the IgGλ alternative pair in the group of low and low-intermediate risk than in the group of high-intermediate risk (p = 0.003 and p = 0.006 respectively). In case of dominant IgGλ secretion, considerably higher IgGκ levels were detected in patients with low or low-intermediate risk than in the group of high-intermediate risk (p = 0.0006 and p = 0.009 respectively). Conclusion: The analysis confirmed a very close correlation between M-protein levels and HLC determination which appears to be an auxiliary or alternative method of M-protein determination with an advantage in case of atypical electrophoresis results (in particular in IgA isotypes) or by very low M-protein concentrations with the benefit of Igκ/Igλ index calculation. The discovered connection between the degree of immune suppression depending on the MGUS risk level and especially the clearly visible benefit of determining the alternative HLC pairs contributes with another aspect to understanding the links between the biology, behaviour, and the potential malignant evolution of MGUS with the advantage of obtaining a well-measurable parameter. The use of the SPA Plus platform seems to be fast, effective, with high prognostic value and, last but not least, even with favourable economic aspects.

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