B Blazek

University Hospital Ostrava, Ostrava, Moravskoslezský, Czech Republic

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Publications (18)49.96 Total impact

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    ABSTRACT: Purpose Treatment of childhood acute myeloid leukemia (AML) was unified in the year 1993 according to acute myeloid leukemia-Berlin–Frankfurt–Munster (AML-BFM) protocols in the Czech Republic. We evaluated data on clinical and therapeutic results in children with AML treated in three subsequent trials, comparing two periods, June 1993 to February 2004 (AML-BFM 93 and 98) vs. March 2004 to December 2009 (AML-BFM 2004 trial). Patients and methods Data of 182 eligible patients were analyzed, 125 in AML-BFM 93 and 98 trials, and 57 in AML-BFM 2004 trial enrolled prior to December 2009. Down syndrome patients were excluded from analysis. Results In studies AML-BFM 93 and 98, 79.2 % of 125 patients achieved complete remission (CR), 19 patients (15.2 %) suffered from early death, 7 (5.6 %) were nonresponders, 33 (33.3 %) relapsed, 12 (12.1 %) died in CR, and 2 patients (2.0 %) developed secondary malignancy. The estimated probability of event-free survival (pEFS) at 5 years was 41.6 %, the overall survival (OS) at 5 years was 46.4 %. In AML-BFM 2004 trial, 93 % of 57 patients attained CR, 3 patients (5.2 %) suffered from early death, 1 (1.8 %) was nonresponder, 16 (30.2 %) relapsed, 2 (3.8 %) died in CR, and 2 patients (3.5 %) developed secondary malignancy. The estimated pEFS at 5 years was 56.1 %, 5-years overall survival (5y-OS) was 73.7 %. Conclusion Gradual improvement of CR rate and OS together with decreasing incidence of toxic deaths in AML patients were achieved because of gain of experience with very intensive modern treatment centralized in a limited number of institutions.
    memo - Magazine of European Medical Oncology 01/2013; 6(1).
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    ABSTRACT: INTRODUCTION: Glucocorticoids, particularly prednisone/ prednisolone and dexamethasone, play a prominent role in the treatment of pediatric patients with acute lymphoblastic leukemia due to their ability to induce apoptosis in susceptible cells. Current therapeutic protocols use prednisone for both the prophase and the induction phase of the therapy because the greater antileukemic activity of dexamethasone is compromised by its high frequency of serious adverse reactions. AIM: To compare, for the first time, the in vitro antileukemic activity of prednisolone alone to that of a combination of prednisolone and dexamethasone using dexamethasone at a very low and presumably safe dosage (1/50 w/w). METHODS: Lymphoblasts were isolated from bone marrow and/or blood samples from children with newly diagnosed acute lymphoblastic leukemia. The cytotoxic activity of prednisolone, dexamethasone and the prednisolone/dexamethasone combination against isolated leukemia cells was analyzed using the MTT cytotoxicity assay. RESULTS: We observed differences in the in vitro antileukemic activity of prednisolone and dexamethasone in 21% of the tested patients. 3% of the children were prednisolone sensitive but dexamethasone resistant, while 18% were prednisolone resistant and dexamethasone sensitive. 32% were sensitive to both glucocorticoids and 18% were resistant to both. Cells from patients with good in vivo responses to prednisone monotherapy were more responsive to prednisolone in vitro than were cells from patients with poor prednisone responses (P<0.07). Importantly, we demonstrated that the use of even a minimal dose (1/50 w/w) of dexamethasone with prednisolone dramatically increases the in vitro anti-leukemic activity of prednisolone (P<0.0006). CONCLUSION: The high inter-individual variability of acute lymphoblastic leukemia responses to glucocorticoids suggest that either patients should be selected for prednisone or dexamethasone treatment on the basis of predictive biomarkers or that prednisone should be used directly in combination with a very low and safe dose of dexamethasone to potentiate its antileukemic activity. The latter option is likely to be cheaper and more efficient, and therefore warrants further clinical investigation to assess its efficacy and safety in treating childhood acute lymphoblastic leukemia.
    Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 10/2012; · 0.99 Impact Factor
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    ABSTRACT: Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction. In this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol. We confirmed the previously published poor correlation between minimal residual disease in blood and marrow at early treatment time points, with levels in bone marrow being higher than in blood in most samples (median 7.9-fold, range 0.04-8,293-fold). A greater involvement of peripheral blood at diagnosis was associated with a higher white blood cell count at diagnosis (P=0.003) and with enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of minimal residual disease in blood lower than 10(-4) was associated with an excellent 5-year relapse-free survival in 78 investigated patients (100% versus 69 ± 7%; P=0.0003). Subgroups defined by the level of minimal residual disease in blood at day 15 (high-risk: ≥ 10(-2), intermediate-risk: <10(-2) and ≥ 10(-4), standard-risk: <10(-4)) partially correlated with bone marrow-based stratification described previously, but the risk groups did not match completely. No other time point analyses were predictive of outcome in peripheral blood, except for a weak association at day 8. Minimal residual disease in peripheral blood at day 15 identified a large group of patients with an excellent prognosis and added prognostic information to the risk stratification based on minimal residual disease at day 33 and week 12.
    Haematologica 08/2011; 96(12):1815-21. · 5.94 Impact Factor
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    ABSTRACT: Hepatitis B immunization of patients with inherited bleeding disorders: personal experiences Hepatitis B vaccination was initiated in 55 patients with inherited bleeding disorders in 1994-2009. Patients received three doses of subcutaneous recombinant vaccine containing 20 mg HBsAg (hepatitis B surface antigen) at 0, 1 and 6 months. Blood samples were obtained at the starting of vaccination, 1-3 months after immunization, and biennially thereafter. The samples were tested for HBsAg, hepatitis B surface and core antibodies (anti-HBs, anti-HBc). Protective anti-HBs level (≥10 IU/l) after immunization was proved in 50 of 51 patients (98 %). Waning of protective anti-HBs antibodies was detected in 4 % and 24 % of patients within 5 and 10 years after vaccination. No HBsAg carrier status or anti-HBc seroconversion were detected. Subcutaneous vaccination against hepatitis B provides long-term protection in patients with inherited bleeding disorders.
    Klinicka mikrobiologie a infekcni lekarstvi 08/2010; 16(4):145-7.
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    ABSTRACT: Mixed phenotype acute leukemia (MPAL) represents a diagnostic and therapeutic dilemma. The European Group for the Immunological Classification of Leukemias (EGIL) scoring system unambiguously defines MPAL expressing aberrant lineage markers. Discussions surrounding it have focused on scoring details, and information is limited regarding its biological, clinical and prognostic significance. The recent World Health Organization classification is simpler and could replace the EGIL scoring system after transformation into unambiguous guidelines. Simple immunophenotypic criteria were used to classify all cases of childhood acute leukemia in order to provide therapy directed against acute lymphoblastic leukemia or acute myeloid leukemia. Prognosis, genotype and immunoglobulin/T-cell receptor gene rearrangement status were analyzed. The incidences of MPAL were 28/582 and 4/107 for children treated with acute lymphoblastic leukemia and acute myeloid leukemia regimens, respectively. In immunophenotypic principal component analysis, MPAL treated as T-cell acute lymphoblastic leukemia clustered between cases of non-mixed T-cell acute lymphoblastic leukemia and acute myeloid leukemia, while other MPAL cases were included in the respective non-mixed B-cell progenitor acute lymphoblastic leukemia or acute myeloid leukemia clusters. Analogously, immunoglobulin/T-cell receptor gene rearrangements followed the expected pattern in patients treated as having acute myeloid leukemia (non-rearranged, 4/4) or as having B-cell progenitor acute lymphoblastic leukemia (rearranged, 20/20), but were missing in 3/5 analyzed cases of MPAL treated as having T-cell acute lymphobastic leukemia. In patients who received acute lymphoblastic leukemia treatment, the 5-year event-free survival of the MPAL cases was worse than that of the non-mixed cases (53+/-10% and 76+/-2% at 5 years, respectively, P=0.0075), with a more pronounced difference among B lineage cases. The small numbers of MPAL cases treated as T-cell acute lymphoblastic leukemia or as acute myeloid leukemia hampered separate statistics. We compared prognosis of all subsets with the prognosis of previously published cohorts. Simple immunophenotypic criteria are useful for therapy decisions in MPAL. In B lineage leukemia, MPAL confers poorer prognosis. However, our data do not justify a preferential use of current acute myeloid leukemia-based therapy in MPAL.
    Haematologica 02/2010; 95(6):928-35. · 5.94 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2009; 24(2):425-8. · 10.16 Impact Factor
  • H Ptoszkova, B Blazek, T Kuhn
    Hamostaseologie 10/2009; 29 Suppl 1:S105-7. · 1.59 Impact Factor
  • Hamostaseologie 10/2009; 29 Suppl 1:S47-9. · 1.59 Impact Factor
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    ABSTRACT: The authors conducted an 8-year prospective non-randomised study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for haematological malignancy. The authors examined prospectively 75 patients (40 male/35 female) aged 2-17 years (median 6.5 years) at the time of diagnosis. The cardioprotection was given to 53 patients (26 male/17 female) and the standard protocol was used in 22 patients (14 male/8 female). The prospective echocardiographic evaluation was done before and after the chemotherapy and every year during the follow-up period. Dynamic stress echocardiography (DSE) was assessed in the final year. The clinical cardiotoxicity was not diagnosed. Higher cumulative doses of anthracycline were given in the dexrazoxane group (234+/-58 mg/m(2), median 240 mg/m(2) versus 203+/-86 mg/m(2), median 210 mg/m(2), P <0.04) and a significantly higher percentage of patients received cumulative doses >240 mg/m(2) of anthracycline ( P <0.05). During the follow-up period, the fractional shortening (FS) declined in the no-dexrazoxane group only in the 8th year and was significantly lower compared to the dexrazoxane group ( P <0.05). The pathological decrease in FS was present in 24% of patients; 41% in the no-dexrazoxane and 17% in the dexrazoxane groups, respectively ( P <0.05). DSE demonstrated lower rest EF and cardiac index (CI) in the no-dexrazoxane group ( P <0.05); however, neither the response of EF and CI to the stress echocardiography nor the exercise tolerance significantly differed between sub-groups. A higher number of patients in the dexrazoxane group had very good exercise tolerance (ET) >3 Watts/kg ( P <0.05) and a lower number responded with a decreased ET <2 Watts/kg ( P <0.05) compared to the no-dexrazoxane group. CONCLUSION: Dexrazoxane seems to reduce the risk of late subclinical cardiotoxicity. Dexrazoxane-treated patients revealed better exercise tolerance; however the haemodynamic response to the stress was no different in both sub-groups.
    European Journal of Pediatrics 11/2005; 164(11):678-84. · 1.91 Impact Factor
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    ABSTRACT: Acute myeloid leukemia (AML) in children is rare. Although more resistant to chemotherapy than acute lymphoblastic leukemia, its responsiveness and survival rates have considerably improved during the last 15 years by virtue of intensification of chemotherapy and due to the better supportive care. Relapses still remain the main cause of treatment failure. Management of children with AML was unified in the Czech Republic in 1993 according to AML-BFM 93 Study protocol. Treatment results were evaluated in 61 patients, of whom 45 (73.8%) achieved complete remission. Five-year event-free-survival (EFS) was found in 42.3%, and overall survival was 45.3%. Prognosis of the standard-risk patients was significantly better than in the high-risk group (EFS 62.5% vs. 29.7%, p = 0.03). The most important prognostic factor was the early treatment response. Compared to chemotherapy, allogeneic stem-cell transplantation did not significantly improve the outcome of high-risk patients. Treatment results of children with AML in the Czech Republic are comparable to those achieved by leading leukemia study groups in the world. The aim of the next study is to increase the complete-remission rate by reducing early deaths.
    Casopís lékar̆ů c̆eských 02/2004; 143(4):257-63.
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    ABSTRACT: Cytogenetic and molecular cytogenetic analysis of 79 childhood acute lymphoblastic leukemias (ALL) revealed chromosomal abnormalities in 76 (96%). Complex karyotypes (a finding of three and more chromosomal aberrations in a karyotype) were identified in 21 (26.6%) out of 79 patients. In 11 patients, complex karyotypes have included common recurrent chromosomal abnormalities, such as translocation t(12;21) in seven cases, t(9;22) in two cases, one case with t(2;1;19) and another one with translocation involving 11q23. In 10 patients, miscellaneous abnormalities were detected. Five patients displayed hyperdiploidy (47 approximately 57 chromosomes), three patients complex karyotypes with deletions of 9p, one patient with two new complex translocations t(2;4;12;13) and t(7;11;20), and the last patient with dic(12;21). The evaluation of the frequency of the chromosomal breaks (>5 per chromosome) showed that chromosomes 2, 4, 5, 7, 9, 12, 13, and 21 were most frequently affected. Survival analysis revealed statistically significant unfavorable event-free survival (EFS) (P=0.013) and decreased overall survival in the group with complex karyotypes (n=21) compared with the other cases (n=58). The evaluation of overexpression profile revealed increased occurrence of double CD13/CD33 positivity in patients with common recurrent chromosomal abnormalities (in 70% of cases); no such cases were registered in the other group (P<0.01).
    Cancer Genetics and Cytogenetics 09/2003; 145(2):161-8. · 1.93 Impact Factor
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    ABSTRACT: Prognosis of children with acute lymphoblastic leukaemia (ALL)--the most common cancer in childhood, has improved remarkably over the last 40 years. The authors report the treatment outcome in children with ALL cured according to ALL-BFM 90 Study protocol in the Czech Republic during the first half of nineties. Children aged 0-18 years were included into the study in 10 centers between 1990 to 1996. Patients were classified into standard-risk (SR), medium-risk (MR) and high-risk (HR) group according to initial leukaemic burden, early treatment response, and genotype of leukaemia. Duration of the chemotherapy was two years. Treatment results were evaluated in 352 children. With a median follow-up of 7.3 years, event-free-survival (EFS) was 71.3% and overall survival 76.4%. EFS was 80.3%, 74% and 28.2% in SR, MR and HR group, respectively. Relapse was diagnosed in 17.8% of the patients. The treatment outcome of children with ALL improved significantly (p = 0.0045) compared to the previous study ALL-BFM 83 (EFS 62%). These results are comparable to those achieved by leading leukaemia study groups in the world.
    Casopís lékar̆ů c̆eských 02/2003; 142(7):404-9.
  • Medical and Pediatric Oncology 09/2002; 39(2):125-7.
  • Medical and Pediatric Oncology 12/2000; 35(5):493-5.
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    ABSTRACT: This study was designed to compare the antileukemic activity of prednisolone and dexamethasone in childhood acute lymphoblastic leukemia (ALL) under in vitro conditions. The chemoresistance of leukemic cells was ascertained by means of a MTT assay in 69 ALL children at diagnosis and the concentration killing 50% of leukemic cells (LCS50) was determined. The children were treated using the protocol ALL-BFM 90/95. Statistical correlations were made among prednisolone (PRED) and/or dexamethasone (DEX) LCS50 and absolute number of blast cells (ANB) on day 0/8 and a new parameter named blast cells clearance (BCC, BCC8 [%] = ANB8: ANB0 x 100) on day 8. Despite the previously published results of Ito et al. (J. Clin. Oncol. 14: 2370-2376, 1996) and Kaspers et al. (MPO 27: 114-121, 1996) on a positive correlation of DEX versus PRED LCS50 (p < 0.002), in our study, we identified 30% of children (21/69) with differential in vitro responsiveness to PRED and DEX. 16% of patients (11/69) were highly sensitive to DEX and resistant to PRED, while 14% of them (10/69) were resistant to DEX and highly sensitive to PRED. The major difference found in our and the other studies was in the processing of leukemic cells. These results were confirmed in a model experiment using the CCRF-CEM line, where we showed that sensitivity to PRED and DEX, but not to other anti-cancer drugs critically depends on manipulation with tumor cells (cryopreservation). Correlation of PRED/DEX in vitro sensitivity values with parameters of in vivo patient's response to PRED monotherapy identified significant association of PRED LCS50 with BCC8 (p < 0.02). It indicates strong linkage of in vitro sensitivity to PRED with percentage of blast cells eliminated from patient blood within the first 8 days of PRED monotherapy.
    Advances in experimental medicine and biology 02/1999; 457:461-71. · 1.83 Impact Factor
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    ABSTRACT: A patient suffering from infantile-onset insulin-dependent diabetes mellitus is reported in whom immune pancytopenia (Evans' syndrome) developed at the age of 2 1/2 years. Hepatosplenomegaly, chronic lymphadenopathy, and elevated levels of immunoglobulins G and M were also present. The course of Evans' syndrome was fatal in this patient. The association of Evans' syndrome with other immune disorders is discussed.
    Pediatric Hematology and Oncology 01/1998; 15(4):353-7. · 0.90 Impact Factor
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    P Plevová, B Blazek
    JNCI Journal of the National Cancer Institute 03/1997; 89(4):326-7. · 14.34 Impact Factor
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    ABSTRACT: We report a fourth case of Hb Nottingham [alpha 2 beta 2 98 (FG5) Val-->Gly] observed in an 8-year-old girl in the Czech Republic with clinical and laboratory symptoms of severe hemolytic anemia. The unstable hemoglobin probably represents a de novo mutation, since the parents of the patient and the two siblings do not exhibit any hematological abnormalities. Splenectomy had a beneficial effect on the degree of hemolysis, as well as on the Hb level.
    Annals of Hematology 08/1994; 69(2):93-5. · 2.87 Impact Factor