Jiri Mayer

University Hospital Brno, Brünn, South Moravian, Czech Republic

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Publications (149)633.32 Total impact

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    ABSTRACT: Xenograft models represent a promising tool to study the pathogenesis of hematological malignancies. To establish a reliable and appropriate in vivo model of aggressive human B-cell leukemia and lymphoma we xenotransplanted four p53-mutated cell lines and one ATM-mutated cell line into immunodeficient NOD/SCID IL2Rγ-null mice. The cell lines MEC-1, SU-DHL-4, JEKO-1, REC-1 and GRANTA-519 were transplanted intraperitoneally or subcutaneously and the engraftment was investigated using immunohistochemistry and flow cytometry. We found significant differences in engraftment efficiency. MEC-1, JEKO-1 and GRANTA-519 cell lines engrafted most efficiently, while SU-DHL-4 cells did not engraft at all. MEC-1 and GRANTA-519 massively infiltrated organs and the whole intraperitoneal cavity showing very aggressive growth. In addition, GRANTA-519 cells massively migrated to the bone marrow regardless of the transplantation route. The MEC-1 and GRANTA-519 cells can be especially recommended for in vivo study of p53-mutated chronic lymphocytic leukemia and ATM-mutated mantle cell lymphoma, respectively.
    Leukemia & lymphoma 04/2015; DOI:10.3109/10428194.2015.1034701 · 2.89 Impact Factor
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    ABSTRACT: The treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) remains a challenging clinical issue. An important treatment option is the use of high-dose corticosteroids. The purpose of this clinical trial was to determine the efficacy and toxicity of an ofatumumab-dexamethasone (O-Dex) combination in relapsed or refractory CLL.The trial was an open-label, multi-center, non-randomized, phase II study. The O-Dex regimen consisted of intravenous ofatumumab (Cycle 1: 300mg on day 1, 2000mg on days 8, 15, 22; Cycles 2-6: 1000mg on days 1, 8, 15, 22) and oral dexamethasone (40mg on days 1-4 and 15-18; Cycles 1-6). The O-Dex regimen was given until best response, or a maximum of 6 cycles.Thirty-three patients (pts) were recruited. Twenty four (73%) pts. completed at least 3 cycles of therapy. The remaining 9 patients were prematurely discontinued due to grade 3/4 infections (7 pts), disease progression (1 pt), or uncontrollable diabetes mellitus (1 pt). Overall responses/complete remissions (ORR/CR) were achieved in 22/5 pts (67/15%). The Median progression-free survival (PFS) was 10 months. In patients with p53 defects (n=8), ORR/CR were achieved in 5/2 pts (63/25%) with a median PFS of 10.5 months. The Median overall survival was 34 months. The grade 3-5 infectious toxicity in 33% of pts represented the most frequent side effect during the treatment period.In conclusion, the O-Dex regimen shows a relatively high ORR and CR with promising findings for PFS and overall survival. The study was registered at www.clinicaltrials.gov (NCT01310101). This article is protected by copyright. All rights reserved.
    American Journal of Hematology 02/2015; 90(5). DOI:10.1002/ajh.23964 · 3.48 Impact Factor
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    ABSTRACT: In a Phase III trial, 485 patients (≥65 years) with newly diagnosed acute myeloid leukemia received decitabine 20 mg/m(2) intravenously for 5 days every 4 weeks or a treatment choice (supportive care or cytarabine 20 mg/m(2) subcutaneously for 10 days every 4 weeks). We summarized overall and progression-free survival by baseline white blood cell count using two analyses: <1, 1-5, >5×10(9)/L; ≤10 or >10×10(9)/L. There were 446 deaths (treatment choice, n=227; decitabine, n=219). Median overall survival was 5.0 (treatment choice) versus 7.7 months (decitabine; nominal P=0.037). Overall survival differences between white blood cell groups were not significant; hazard ratios (HRs) favored decitabine. Significant progression-free survival differences favored decitabine for groups 1-5×10(9)/L (P=0.005, HR =0.67), greater than 5×10(9)/L (P=0.027, HR =0.71), and up to 10×10(9)/L (P=0.003, HR =0.72). There was a trend toward improved outcome with decitabine, regardless of baseline white blood cell count.
    Hematology Research and Reviews 01/2015; 6:25. DOI:10.2147/JBM.S64067
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    ABSTRACT: TP53 gene defects represent a strong adverse prognostic factor for patient survival and treatment resistance in chronic lymphocytic leukemia (CLL). Although various methods for TP53 mutation analysis have been reported, none of them allow the identification of all occurring sequence variants, and the most suitable methodology is still being discussed. The aim of this study was to determine the limitations of commonly used methods for TP53 mutation examination in CLL and propose an optimal approach for their detection. We examined 182 CLL patients enriched for high-risk cases using denaturing high-performance liquid chromatography (DHPLC), functional analysis of separated alleles in yeast (FASAY), and the AmpliChip p53 Research Test in parallel. The presence of T53 gene mutations was also evaluated using ultra-deep next generation sequencing (NGS) in 69 patients. In total, 79 TP53 mutations in 57 (31 %) patients were found; among them, missense substitutions predominated (68 % of detected mutations). Comparing the efficacy of the methods used, DHPLC and FASAY both combined with direct Sanger sequencing achieved the best results, identifying 95 % and 93 % of TP53-mutated patients. Nevertheless, we showed that in CLL patients carrying low-proportion TP53 mutation, the more sensitive approach, e.g., ultra-deep NGS, might be more appropriate. TP53 gene analysis using DHPLC or FASAY is a suitable approach for mutation detection. Ultra-deep NGS has the potential to overcome shortcomings of methods currently used, allows the detection of minor proportion mutations, and represents thus a promising methodology for near future.
    Tumor Biology 12/2014; 36(5). DOI:10.1007/s13277-014-2971-0 · 3.61 Impact Factor
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    ABSTRACT: Introduction: Chemoimmunotherapy has become a standard approach in previously untreated and also in pretreated CLL. Addition of Rituximab to FC in fit patients has proven superior to chemotherapy alone and more recently aCD20 treatment was shown to improve outcomes in patients treated with Chlorambucil, suggesting that immunotherapy may be of benefit, independent of the chosen chemotherapy backbone. In follicular and mantle cell lymphoma rituximab maintenance treatment has become a clinical standard. While we and others have presented Phase II data on the feasibility of Rituximab maintenance after chemoimmunotherapy induction, there are currently no available randomized data on the efficacy of such an approach. Study design: Patients were recruited after informed consent at the end of any Rituximab-containing induction treatment in 1st or 2nd line that achieved at least a PR. Excluded were patients with uncontrolled bacterial or viral infections and conditions that might severely affect life-expectancy (such as other malignancy, heart disease etc). The trial was registered at clinicaltrials.gov with the identifier NCT01118234. Randomization was stratified by country, line of treatment, induction response and type of induction regimen. Primary endpoint was PFS and a planned sample-size of 256 patients was calculated. All patients were recruited in participating centers between September 2009 and December 2013. An interim analysis was planned to be conducted after half of the planned events (i.e. 46) were observed and is presented here. Results: The current analysis includes 263 patients enrolled into the trial. Patients had a median age of 63 years, 28.9% were female and 80.6% were enrolled after 1st induction treatment. Hierarchical FISH cytogenetic risk was available in 221 patients: del17p 3.1%, del11q 27.6%, tris 12 10.8%, del13q 36.2%, and normal FISH karyotype 21.2%. IgVH Mutation state was available in 161 patients at time of interim analysis and 67% were unmutated. The induction regimen was FCR in 73.5% and BR in 20.2%, the response to induction treatment was CR/CRi in 58% and PR in 41.8% of patients and 57% scored negative in an 8-colour MRD flowcytometric analysis after induction. Rituximab treatment was allocated to 134 patients and 129 were in the observation arm. No significant imbalances in randomization were found in the above-mentioned parameters. Median observation time is currently 17.3 months. Regarding toxicities the current state of monitoring allows an analysis on the level of SAEs only. SAE causes were well balanced between arms with the exception of infectious SAEs - 32 in the rituximab and 22 in the observation arm, 3 deaths were attributed to infections (1 in the rituximab arm and 2 in the observation arm) - and secondary malignancies (8 in the rituximab arm vs. 1 in the observation arm). Four of the neoplasms in the rituximab arm were localized non-melanoma skin cancers and the 2 deaths from malignomas occurred one in each arm. Regarding efficacy, currently 27.9% have progressed in the observation arm and 14.9% in the rituximab arm. Ten patients died in the observation arm and 7 in the rituximab arm. The primary endpoint (PFS) is significantly in favour of rituximab maintenance (see Fig) with a p-value of 0.007 and a PFS at 17.3 months of 85.1% vs.75.5% in rituximab vs. observation arms, respectively. To account for toxicities and secondary neoplasms an EFS was calculated counting secondary malignancies, termination of treatment due to toxicities, progression or death as events. In this analysis the benefit was preserved, albeit with a lower p-value of 0.03. The observed benefit seemed independent from response after induction (CR vs. PR), but associated with positive MRD state after induction. Further factors that influenced the benefit in exploratory subgroup analyses were sex, cytogenetics, IgVH and B-symptoms at diagnosis. Conclusions: Rituximab maintenance after chemoimmunotherapy induction in CLL seems feasible, although with an increase in infectious complications, and shows signs of efficacy in this interim analysis. The presented interim analysis refutes the alternative hypothesis and allows the trial to continue. Exploratory analyses suggest that with longer follow-up it may be possible to define subpopulations with larger benefit from extended immunotherapy. Figure: PFS by treatment arm (Observation arm: …; Rituximab arm: __) Disclosures: Greil: Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Sanofi Aventis: Honoraria; GSK: Research Funding; Ratiopharm: Research Funding. Off Label Use: Rituximab in Maintenace Treatment of CLL. Kozak: Roche: Honoraria, Travel grants Other. Girschikofsky: Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Petzer: Celgene: Honoraria, unrestricted grant Other. Egle: Roche: Honoraria, Research Funding, Travel Grants Other. See more of: 642. CLL: Therapy, excluding Transplantation: Phase 3 Trials and More See more of: Oral and Poster Abstracts << Previous Abstract | Next Abstract >> *signifies non-member of ASH ASH logo American Society of Hematology 2021 L Street NW, Suite 900, Washington, DC 20036 | Phone 202-776-0544 | Fax 202-776-0545 Contact Us | Terms of Service | Privacy Policy | RSS Copyright ©2014 American Society of Hematology
    ASH 2014, San Francisco; 12/2014
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    ABSTRACT: ABSTRACT Early-stage follicular lymphoma (FL) has traditionally been treated with involved-field radiotherapy (RT). Rituximab (R) is low-toxic, efficient systemic therapy for FL; but there are no data about its clinical impact in early FL. We retrospectively analyzed 93 patients with stage I-II indolent FL treated with RT (n=65), or RT+R (n=14) or with R alone (n=14). Median follow up was 5.0 years for RT patients, 2.8 years for the RT+R subgroup and 2.5 years for R patients. The complete response rate was 92%, 100% and 86% (ns) and the median PFS was 3.3 years, not reached, and 4.9 years (p.035) for the RT, RT+R and R arm, with no impact on overall survival. Rituximab combined with RT seems to give better results in terms of global FL control, but longer follow-up and prospective comparison are needed to verify these results.
    Leukemia and Lymphoma 11/2014; DOI:10.3109/10428194.2014.990010 · 2.89 Impact Factor
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    ABSTRACT: Abnormalities in ATM and TP53 genes represent important predictive factors in chronic lymphocytic leukemia (CLL). However, the efficacy of CD20 targeting immunotherapy is only poorly defined in the affected patients. Therefore we tested the in vitro response to ofatumumab (OFA) and rituximab (RTX) in 75 CLL samples with clearly defined p53 or ATM inactivation. Using standard conditions allowing complement-dependent cytotoxicity (CDC), i.e. 10 μg/mL of antibodies and 20% active human serum, we observed clear differences among the tested genetic categories: ATM-mutated samples (n = 17) represented the most sensitive, wild-type samples (n = 31) intermediate, and TP53-mutated samples (n = 27) the most resistant group (ATM-mut vs. TP53-mut: P = 0.0005 for OFA and P = 0.01 for RTX). The response correlated with distinct levels of CD20 and critical complement inhibitors CD55 and CD59; CD20 level median was the highest in ATM-mutated and the lowest in TP53-mutated samples (difference between the groups P ˂ 0.01), while the total level of complement inhibitors (CD55 plus CD59) was distributed in the opposite manner (P ˂ 0.01). Negligible response to both OFA and RTX was noted in all cultures (n = 10) tested in the absence of active serum, which strongly indicated that CDC was a principal cell death mechanism. Our study shows that (1) common genetic defects in CLL cells significantly impact a primary response to anti-CD20 monoclonal antibodies and (2) ATM-mutated patients with currently poor prognosis may potentially benefit from immunotherapy targeting CD20.
    Experimental Hematology 10/2014; 42(10). DOI:10.1016/j.exphem.2014.06.003 · 2.81 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5198-5198. DOI:10.1158/1538-7445.AM2014-5198 · 9.28 Impact Factor
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    ABSTRACT: Background Antiviral resistance development is a serious complication of human cytomegalovirus virostatic therapy caused by mutations in UL 97 and/or UL54 genes. Objectives To determinate the presence of sensitive and mutant strains in patients developing antiviral resistance. Study design We used three different molecular biological methods for mutation analysis–restriction fragment length polymorphism, sequencing and real-time PCR approach. Results We describe three allogeneic hematopoietic stem cell transplant patients developing the GCV resistant HCMV strains manifested by virostatic treatment failure. In these patients we identified UL97 mutations L595S, A594 V and A594 T and monitored the dynamics of coexisted sensitive/resistant strains. We confirmed the presence of mixed HCMV populations and in two patients a phenomenon of sensitive strain repopulation which occurred after 6.5 months and 1 month after removing GCV pressure. Conclusions Our results show changes in proportions of sensitive/resistant subpopulations over time but other studies would be required to demonstrate the beneficial impact of their monitoring on clinical outcome.
    Journal of Clinical Virology 10/2014; 61(2). DOI:10.1016/j.jcv.2014.07.008 · 3.47 Impact Factor
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    American Journal of Hematology 10/2014; 89(10). DOI:10.1002/ajh.23794 · 3.48 Impact Factor
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    ABSTRACT: Objectives Lung cancer with the ALK rearrangement constitutes only a small fraction of patients with non-small cell lung cancer (NSCLC). However, in the era of molecular-targeted therapy, efficient patient selection is crucial for successful treatment. In this context, an effective method for EML4-ALK detection is necessary. We developed a new highly sensitive variant specific TaqMan based real time PCR assay applicable to RNA from formalin-fixed paraffin-embedded tissue (FFPE). Materials and methods This assay was used to analyze the EML4-ALK gene in 96 non-selected NSCLC specimens and compared with two other methods (end-point PCR and break-apart FISH). Results EML4-ALK was detected in 33/96 (34%) specimens using variant specific real time PCR, whereas in only 23/96 (24%) using end-point PCR. All real time PCR positive samples were confirmed with direct sequencing. A total of 46 specimens were subsequently analyzed by all three detection methods. Using variant specific real time PCR we identified EML4-ALK transcript in 17/46 (37%) specimens, using end-point PCR in 13/46 (28%) specimens and positive ALK rearrangement by FISH was detected in 8/46 (17.4%) specimens. Moreover, using variant specific real time PCR, 5 specimens showed more than one EML4-ALK variant simultaneously (in 2 cases the variants 1 + 3a + 3b, in 2 specimens the variants 1 + 3a and in 1 specimen the variant 1 + 3b). In one case of 96 EML4-ALK fusion gene and EGFR mutation were detected. All simultaneous genetic variants were confirmed using end-point PCR and direct sequencing. Conclusion Our variant specific real time PCR assay is highly sensitive, fast, financially acceptable, applicable to FFPE and seems to be a valuable tool for the rapid prescreening of NSCLC patients in clinical practice, so, that most patients able to benefit from targeted therapy could be identified.
    Lung cancer (Amsterdam, Netherlands) 07/2014; 85(1). DOI:10.1016/j.lungcan.2014.04.002 · 3.74 Impact Factor
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    ABSTRACT: This multicentre study focused on monitoring imatinib mesylate (IMA) trough plasma (C trough) and intracellular (IMA C intrac) concentrations in 228 chronic myelogenous leukaemia patients. The median of measured IMA C trough in our patient group was 905.8 ng ml (range: 27.7–4628.1 ng/ml). We found a correlation between IMA C trough and alpha 1-acid glycoprotein plasma concentrations (rS = 0.42; p < 0.001). All other analysed parameters revealed only weak (gender, dose of IMA per kg) or not significant (age, albumin, creatinine plasma concentration or body mass index) impact on measured IMA C trough. The IMA C trough decreased during the first 6 months and significantly increased later during treatment. The IMA C trough at the first month of therapy did not differ between patients with and without an optimal response at the 12th (p = 0.724) and 18th month (p = 0.135) of therapy. There were no significant differences in medians of IMA C trough between both groups measured during the first year of treatment. The IMA C intrac during the first month were not different between patients with and without an optimal response at the 6th (p = 0.273) and the 12th month (p = 0.193) of therapy. Our data obtained from real life clinical practice did not find a benefit of routine and regular IMA C trough nor IMA C intrac therapeutic drug monitoring in chronic myelogenous leukaemia patients or for subsequent adjustments of the IMA dose based on these results. Moreover, actual alpha 1-acid glycoprotein plasma concentration should be used for proper interpretation of IMA C trough results.
    Hematological Oncology 06/2014; DOI:10.1002/hon.2091 · 2.36 Impact Factor
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    ABSTRACT: Rapid differential diagnostics of pulmonary infiltrates suspected of invasive fungal disease in an immunocompromised host and early initiation of effective antifungal therapy are crucial for patient outcomes. There are no serological tests available to detect mucormycetes; therefore, PCR-based methods are highly suitable. We validated our previously published PCR followed by high-resolution melt analysis (PCR/HRMA) to detect Rhizopus spp., Rhizomucor pusillus, Lichtheimia corymbifera, and Mucor spp. in bronchoalveolar lavage (BAL) samples from immunocompromised patients who were at risk of invasive fungal disease. All PCR/HRMA-positive samples were retested using novel real-time quantitative PCR (RQ PCR) assays specific to the species identified. In total, between January 2009 and December 2012 we analyzed 99 BAL samples from 86 patients with pulmonary abnormalities using PCR/HRMA. Ninety (91%) BAL samples were negative, and 9 (9%) samples were positive. The sensitivity and specificity of PCR/HRMA were 100% and 93%, respectively. By combining the positive results of PCR/HRMA with positive RQ PCR results, the specificity was raised to 98%. PCR/HRMA, due to its high negative predictive value (99%), represents a fast and reliable tool for routine BAL sample screening for the differential diagnosis of pulmonary infiltrates in immunocompromised patients for the four most clinically important mucormycetes.
    Journal of Clinical Microbiology 05/2014; 52(8). DOI:10.1128/JCM.00637-14 · 4.23 Impact Factor
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    ABSTRACT: In the two consecutive German studies III and IIIA on chronic myeloid leukemia, between 1995 and 2004, 781 patients were randomized to receive either allogeneic hematopoietic stem cell transplantation with a related donor or continued drug treatment. Despite comparable transplantation protocols and most centers participating in both studies, the post-transplant survival probabilities for patients transplanted in first chronic phase were significantly higher in study IIIA (144 patients) than in study III (113 patients). Prior to the decision on a combined analysis of both studies, reasons for this discrepancy had to be investigated. The Cox proportional hazard cure model was used to identify prognostic factors for post-transplant survival. Donor-recipient matching for human leukocyte antigen, patient age, time between diagnosis and transplantation, and calendar time showed a significant influence on survival and/or the incidence of cure. Added as a further factor, affiliation to study IIIA had no significant impact any longer. Discrepancies in influential prognostic factors explained the different post-transplant survival probabilities between the studies. The significance of calendar time suggests a lack of consistency of transplantation practice over time. Accordingly, the prerequisite for a common assessment of overall survival in the two randomized transplantation arms was not met. Moreover, our analyses provide an independent validation of established prognostic factors and their cutoffs. The statistical approach in investigating and modeling potential prognostic factors for survival sets an example for the examination of studies with unexpected outcome differences in concurrent treatment arms.
    Journal of Cancer Research and Clinical Oncology 04/2014; DOI:10.1007/s00432-014-1662-y · 3.01 Impact Factor
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    ABSTRACT: This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASISION trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete cytogenetic response was 3 versus 6 months with dasatinib versus imatinib. At 3 and 6 months, the proportion of patients with BCR-ABL transcript levels ≤ 10% was higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival (PFS) and overall survival (OS) in both arms. First-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early molecular response was predictive of improved PFS and OS, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors. This study was registered at ClinicalTrials.gov: NCT00481247.
    Blood 12/2013; 123(4). DOI:10.1182/blood-2013-06-511592 · 10.43 Impact Factor
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    ABSTRACT: MicroRNA (miRNA) expression is deregulated in many tumors including chronic lymphocytic leukemia (CLL). Although the particular mechanism responsible for their aberrant expression is not well characterized, the presence of mutations and single nucleotide polymorphisms (SNP) in miRNA genes, possibly affecting their secondary structure and expression, has been described. In CLL, however, the impact and frequency of such variations have yet to be elucidated. Using a custom resequencing microarray, we screened sequence variations in 109 cancer related pre-miRNAs in 98 CLL patients. Additionally, the primary regions of miR-29b-2/29c were analyzed by Sanger sequencing in another cohort of 213 CLL patients. Altogether, we describe 6 novel miR-sequence variations and the presence of SNPs (n=27), most of which changed the miR-secondary structure. Moreover, some of the identified SNPs have a significantly different frequency in CLL when compared to a control population. Additionally, we identified a novel variation in miR-16-1 that had not been previously described in CLL patients. We show that this variation affects the expression of mature miR-16-1. We also show that the expression of another miRNA with pathogenetic relevance for CLL, namely miR-29b-2, is influenced by the presence of a polymorphic insertion which is more frequent in CLL than in a control population. Altogether, these data suggest that sequence variations may occur during CLL development and/or progression.
    Carcinogenesis 12/2013; 35(5). DOI:10.1093/carcin/bgt396 · 5.27 Impact Factor
  • Leukemia & lymphoma 10/2013; 55(8). DOI:10.3109/10428194.2013.858150 · 2.89 Impact Factor
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    ABSTRACT: In chronic lymphocytic leukemia, usually a monoclonal disease, multiple productive immunoglobulin heavy chain gene rearrangements are identified sporadically. Prognostication of such cases based on immunoglobulin heavy variable gene mutational status can be problematic, especially if the different rearrangements have discordant mutational status. To gain insight into the possible biological mechanisms underlying origin of the multiple rearrangements, we performed a comprehensive immunogenetic and immunophenotypic characterization of 31 cases with the multiple rearrangements identified in a cohort of 1147 chronic lymphocytic leukemia patients. For the majority of cases (25/31), we provide evidence for the co-existence of at least two B lymphocyte clones with chronic lymphocytic leukemia phenotype. We also identified clonal drifts in serial samples, likely driven by selection forces. More specifically, higher immunoglobulin variable gene identity to germline and longer complementarity determining region 3 were preferred in persistent or newly appearing clones, a phenomenon more pronounced in patients with stereotyped B cell receptors. Finally, we report that other factors, such as TP53 gene defects and therapy administration, influence clonal selection. Our findings are relevant to clonal evolution in the context of antigen stimulation and transition of monoclonal B-cell lymphocytosis to chronic lymphocytic leukemia.
    Haematologica 09/2013; 99(2). DOI:10.3324/haematol.2013.087593 · 5.87 Impact Factor
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    ABSTRACT: Using the data of 723 chronic myeloid leukemia (CML) patients in the chronic phase, we analyzed the prognostic value of the Sokal, Euro, and EUTOS scores as well as the level of BCR-ABL1 and the achievement of complete cytogenetic response (CCgR) at 3 months of imatinib therapy in relation to the so-called current survival measures: the current cumulative incidence (CCI) reflecting the probability of being alive and in CCgR after starting imatinib therapy; the current leukemia-free survival (CLFS) reflecting the probability of being alive and in CCgR after achieving the first CCgR; and the overall survival. The greatest difference between the CCI curves at 5 years after initiating imatinib therapy was observed for the BCR-ABL1 transcripts at 3 months. The 5-year CCI was 94.3% in patients with BCR-ABL1 transcripts ≤ 10% and 57.1% in patients with BCR-ABL1 transcripts > 10% (p=0.005). Therefore, the examination of BCR-ABL1 transcripts at 3 months may help in early identification of patients who are likely to perform poorly with imatinib. On the other hand, CLFS was not significantly affected by the considered stratifications. In conclusion, our results indicate that once the CCgR is achieved, the prognosis is good irrespective of the starting prognostic risks.
    American Journal of Hematology 09/2013; 88(9). DOI:10.1002/ajh.23508 · 3.48 Impact Factor
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    ABSTRACT: Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors (TKIs), mandate regular updating of concepts and management. An ELN expert panel reviewed prior and new studies, to update recommendations made in 2009. We recommend as initial treatment imatinib or nilotinib or dasatinib. Response is assessed with standardized RQ-PCR and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward, define optimal response, while >10% at 6 months and >1% from 12 months onward define failure, mandating a change of treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete CyR (CCyR) from 6 months onward define optimal response, while no CyR (Ph+>95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward, define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to 2nd line therapy. Specific recommendations are made for patients in accelerated and blastic phase, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or can be enrolled in controlled studies of treatment discontinuation, once a deeper molecular response is achieved.
    Blood 06/2013; 122(6). DOI:10.1182/blood-2013-05-501569 · 10.43 Impact Factor

Publication Stats

3k Citations
633.32 Total Impact Points

Institutions

  • 2003–2015
    • University Hospital Brno
      • • Department of Internal Medicine, Hematology and Oncology
      • • Department of Clinical Microbiology
      Brünn, South Moravian, Czech Republic
  • 1995–2014
    • Masaryk University
      • • Faculty of Medicine
      • • Department of Internal Medicine, Hematology and Oncology
      • • Ústav preventivního lékařství
      • • Second Department of Internal Medicine
      Brünn, South Moravian, Czech Republic