Jerzy R Kowalczyk

University of Lodz, Łódź, Łódź Voivodeship, Poland

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Publications (182)205.78 Total impact

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    ABSTRACT: In Europe, 6,000 young people die of cancer yearly, the commonest disease causing death beyond the age of 1 year. In addition, 300,000–500,000 European citizens are survivors of a childhood cancer and up to 30% of them have severe long-term sequelae of their treatment. Increasing both cure and quality of cure are the two goals of the European paediatric haematology/oncology community. SIOPE coordinates and facilitates research, care and training which are implemented by the 18 European study groups and 23 national paediatric haematology/oncology societies. SIOPE is the European branch of the International Society of Paediatric Oncology and one of the six founding members of the European Cancer Organisation. SIOPE is preparing its strategic agenda to assure long-term sustainability of clinical and translational research in paediatric malignancies over the next 15 years. SIOPE tackles the issues of equal access to standard care and research across Europe and improvement of long term follow up. SIOPE defined a comprehensive syllabus for training European specialists. A strong partnership with parent, patient and survivor organisations is being developed to successfully achieve the goals of this patient-centred agenda. SIOPE is advocating in the field of EU policies, such as the Clinical Trials Regulation and the Paediatric Medicine Regulation, to warrant that the voice of young people is heard and their needs adequately addressed. SIOPE and the European community are entirely committed to the global agenda against childhood cancers to overcome the challenges to increasing both cure and quality of cure of young people with cancer. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 04/2014; · 2.35 Impact Factor
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    ABSTRACT: Background Currently, there are three major maturational stages of CD19 antigen expressing B-cell precursors (hematogones). In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the malignant counterpart of hematogones, the leukemic blasts share common phenotypic features. The aim of the study was to enumerate the actual differences between the leukemic blasts in the CD10+ and CD10− subgroups of BCP-ALL and hematogones by assessing the expression of the antigens: TdT, CD34, CD45, CD10, CD38, CD20 and CD22.Methods To enable quantitative assessment of antigen expression on the different cell types, an objective scale of antigen expression was developed, the basis of which was direct fluorescence measurement using multicolor flow cytometry.ResultsAll cases of CD10+ BCP-ALL clustered with type 1 hematogones. Among CD10−- BCP-ALL subgroup, 54.5%, 27.3% and 18.2% of cases clustered with type 1, 2 and 3 hematogones, respectively. In contrast to the CD10− blasts, the CD10+ blasts exhibited significantly higher levels of TdT, CD22, CD34 and CD20 expression. Conversely, CD10− blasts showed significantly higher expression of CD45 than CD10+ blasts, and a higher rate of CD45 antigen overexpression than CD10+ blasts (54.5% vs. 14.9% of cases, respectively).Conclusions Multiparameter flow cytometry combined with the use of absolute antigen expression scale based on direct fluorescence measurement, has enabled a clear distinction between blasts in BCP-ALL cases and their normal counterparts. This novel and previously undescribed method has allowed the comparative analysis of antigen expression between leukemic blasts and different types of their normal counterparts. © 2014 International Clinical Cytometry Society
    Cytometry Part B Clinical Cytometry 04/2014; · 2.23 Impact Factor
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    ABSTRACT: Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood cancer characterized by peak of incidence between 2 and 5 years. Since recently conducted genome-wide association (GWA) studies revealed that common low-penetrance susceptibility allele at 7p12.2 (IKZF1 gene) confers increased risk of pediatric ALL, we investigate whether risk allele at rs4132601 also coexists with well-established prognostic factors among 508 Polish pediatric patients with newly diagnosed ALL. Additionally, in order to verify whether the risk allele is favored by somatic tumor evolution, we examined the incidence of IKZF1 deletions in leukemic clones derived from 153 previously genotyped pediatric ALL cases. Results of the analysis provide statistically significant support for an association between rs4132601 polymorphic site and age at diagnosis of childhood ALL (p=0.04). No association between allele variant and IKZF1 deletions occurrence was found. These data are further evidence of a biological role of gene variants in ALL development.
    Leukemia & lymphoma 03/2014; · 2.40 Impact Factor
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    ABSTRACT: From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups. For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option). At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI. The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.
    Journal of Clinical Oncology 12/2013; · 18.04 Impact Factor
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    ABSTRACT: Three NOD2 polymorphisms (SNP8 (2104C>T, Arg702Trp), SNP12 (2722G>C, Gly908Arg) and SNP13 (3020insC, Leu1007 fsins C)), identified as disease-associated variants in Crohn's disease (CD), have recently been suggested as gene markers of the outcome of hematopoietic stem cell transplantation (HSCT). In the present multicenter study (464 donor-recipient pairs) we focused on the effect of NOD2 mutation(s) on the risk of infections and acute graft-versus-host disease (aGvHD). The presence of SNP13 either in recipients or in donors or in both was more frequently seen in cases having than lacking sepsis (9/48 vs 33/386, p=0.046). The presence of SNP8 (recipient and/or donor positive) was associated with a higher rate of Herpes viruses reactivation (17/21 vs 86/173, p= 0.007). In the SNP8 positive group also a trend for a higher rate of bacteremia well controlled by antibiotics was found (9/10 vs 47/81, p=0.106). In contrast, the presence of SNP13 in recipient and/or donor resulted in a poor response to antibiotics (5/11 vs 9/10, p=0.042). A statistically significant association between the presence of NOD2 SNPs and acute grade > II GvHD was found in a subgroup of HSCT patients who received transplants from unrelated donors, with a myeloablative conditioning regimen that included anti-thymocyte globulin (ATG). In this subgroup of patients their donor positivity for any SNPs investigated (7/18 vs 17/113, p=0.036) and independently only the presence of SNP8 (4/8 vs 20/123, p=0.055) were associated with severe grade >= II aGvHD. In conclusion, SNP8 positivity in donors or recipients makes patients more prone to Herpes viruses reactivation and bacteremia but not sepsis. Septic complications were associated with SNP13 polymorphism. SNP8 in donors constitutes a risk factor of severe aGvHD but only if patients were transplanted from unrelated donors and received ATG as part of a conditioning regimen.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2013; · 3.15 Impact Factor
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    Journal of Ultrasonography. 12/2013;
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    ABSTRACT: Four hundred and ninety-five patients (390 and 105 grafted from unrelated and sibling (SIB) donors, respectively) and their donors were analyzed for the impact of interleukin-10 (IL-10) promoter genotype [rs18000896 (-1082 G/A), rs18000871 (-819 C/T) and rs18000872 (-592 C/A)] on the outcome of hematopoietic stem cell transplantation (HSCT). Patients having ACC haplotype were at a lower risk of acute graft versus host disease (aGvHD, grade > I) if transplanted from human leukocyte antigen (HLA) well-matched (10/10) unrelated donors (20/135 vs 39/117, P < 0.001, Pcorr = 0.002), which was not seen if patients were transplanted from either sibling (SIB) or poorly matched (<10/10) unrelated donors (MUD). In addition, GCC haplotype positive recipients of unrelated donor transplants tended to be more susceptible to aGvHD (68/199 vs 39/169, P = 0.019, Pcorr = 0.057). Multivariate logistic regression analysis in the MUD transplanted group showed that donor-recipient human leukocyte antigen (HLA) mismatch [odds ratio (OR) = 3.937, P = 0.001] and a lack of ACC haplotype in recipients (OR = 0.417, P = 0.013) played a significant role as independent risk factors of aGvHD grade > I. ACC carriers had higher proportions of FoxP3+ lymphocytes gated in CD4+ lymphocytes as compared with patients with other IL-10 haplotypes. It was seen at the time of hematological recovery (mean ± SEM: 3.80 ± 0.91% vs 2.06 ± 0.98%, P = 0.012) and 2 weeks later (5.32 ± 0.87% vs 2.50 ± 0.83%, P = 0.013); -592 C/A polymorphism was separately analyzed and it was found that AA homozygotes tended to have a higher incidence of aGvHD (8/15 vs 116/456, P = 0.034) and low proportions of FoxP3 CD4+ lymphocytes in blood (0.43 ± 0.22% vs 4.32 ± 0.71%, P = 0.051) measured 2 weeks after hematological recovery. Functional IL-10 polymorphism associated features influenced the risk of aGvHD with a positive effect of ACC on the pool of Treg in blood.
    Tissue Antigens 12/2013; 82(6):387-96. · 2.93 Impact Factor
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    ABSTRACT: Despite the increase of cure rates in the treatment of children with cancer there is a significant discrepancy in the outcome within Europe. Data are showing us that there is a difference of 20% in outcomes for young people with cancer when comparing North and Western Europe with Central and Eastern Europe. One of the most important necessities, in order to be able to have comparable results and equitable outcomes about inequalities, is to have the Principle Treatment Centres, meeting a minimum level of standards and being accessible to continuously updated 'best practice'. The European Society of Paediatric Oncology (SIOPE) has initiated a study in order to monitor the current situation of the European Standards of Paediatric Oncology Centres. The results of the study showed disparities of Standards of Care in the Treatment Centres across Europe. Therefore SIOPE initiated a project aimed at improving the Quality-of-Care of children and adolescents with cancer and to assess the relevant organisational aspects within paediatric oncology. At the first European Union (EU) Conference in Warsaw 2009, an agreement was obtained from all involved stakeholders to initiate the creation of Pan-European guidelines entitled 'European Standards of Care for Children with Cancer'. The guidelines outlined in this document represent the minimum standards of care that should be implemented at the EU level. Describing the different aspects of Care over 15 chapters and available in more than 16 different EU languages these guidelines are used as tools for both professionals and parent/patients groups in order to advocate 'improved standards across EU'.
    European journal of cancer (Oxford, England: 1990) 11/2013; · 4.12 Impact Factor
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    ABSTRACT: Children with Down syndrome (DS) have an increased risk of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995-2004. Non-DS BCP-ALL patients from the DCOG and BFM were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26±2% vs. 15±1%; p<0.001) and 2-year treatment-related mortality (TRM) (7±1% vs. 2.0±<1%; p<0.0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64±2% vs. 81±2%; p<0.0001) and overall survival (74±2% vs. 89±1%; p<0.0001). Independent favorable prognostic factors include age<6 years (hazard ratio [HR]=0.58, p=0.002), white blood cell count (WBC) <10x10(9)/L (HR=0.60, p=0.005) and ETV6-RUNX1 (HR=0.14; p=0.006) for EFS, age (HR=0.48, p<0.001), ETV6-RUNX1 (HR 0.1, p=0.016) and high hyperdiploidy (HeH) (HR 0.29, p=0.04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment-phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy, and reduction of therapy in newly identified good-prognosis subgroups.
    Blood 11/2013; · 9.06 Impact Factor
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    Blood Cells Molecules and Diseases 06/2013; 51(1):66–68. · 2.26 Impact Factor
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    ABSTRACT: Childhood cancer is a major global health issue. Every year, almost 100 000 children die from cancer before the age of 15 years, more than 90% of them in resource-limited countries. Here, we review the key policy issues for the delivery of better care, research, and education of professionals and patients. We present a key list of time-limited proposals focusing on change to health systems and research and development. These include sector and system reforms to make care affordable to all, policies to promote growth of civil society around both cancer and Millennium Development Goals, major improvements to public health services (particularly the introduction of national cancer plans), improved career development, and increased remuneration of specialist health-care workers and government support for childhood cancer registries. Research and development proposals focus on sustainable funding, the establishment of more research networks, and clinical research specifically targeted at the needs of low-income and middle-income countries. Finally, we present proposals to address the need for clinical trial innovation, the complex dichotomy of regulations, and the threats to the availability of data for childhood cancers.
    The Lancet Oncology 03/2013; 14(3):e125-35. · 25.12 Impact Factor
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    ABSTRACT: Since 1983 four consecutive unified regimens: acute myeloid leukemia-Polish pediatric leukemia/lymphoma study group (AML-PPLLSG) 83, AML-PPLLSG 94, AML-PPLLSG 98 and AML-BFM 2004 Interim, for AML have been conducted by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). In this paper, we review four successive studies on the basis of acute myeloid leukemia-Berlin-Frankfurt-Munster (AML-BFM) protocol, in which a stepwise improvement of treatment outcome was observed. Treatment results of the last protocol AML-BFM 2004 Interim are presented in detail. Three hundred and three patients with de novo AML were treated according to the AML-BFM 2004 Interim at 15 Polish centers from January 1, 2005 to June 30, 2011. A confrontation with previous treatment periods was based upon historical, already published data. In four consecutive periods, 723 children were eligible for evaluation (208, 83, 195, and 237, respectively). Complete remission rates in consecutive periods were: 71, 68, 81 and 87 %, respectively. The 5-year overall survival rates, event-free survival rates, and relapse-free survival rates were 33, 32, and 45%, respectively for AML-PPLLSG 83 regimen; 38, 36, and 53 % respectively for AML-PPLLSG 94 regimen; 53, 46, and 65 % respectively for AML-PPLLSG 98 regimen, and 63, 52, and 64 % for AML-BFM Interim 2004, respectively. Incidence of early deaths and that due to complications (mainly infections) in the first remission decreased over time from 22 to 4.6 % and from 10 to 5.9 %, respectively. Despite continuous improvement in the treatment outcome, the number of failures still remains too high. Further progress seemed to be possible due to continued cooperation of oncology centers within large international study groups.
    memo - Magazine of European Medical Oncology 02/2013; 6(1):54-62.
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    ABSTRACT: Defect in function of tumor suppressor genes may lead to initiation/progression of leukemias. RB1, CDKN2A and TP53 gene alterations are found in acute lymphoblastic leukemia (ALL) in children. Data showing a contribution of these alterations to the pathomechanism of leukemias are contradictory and their impact on a disease course still remains undefined. The main aim of the study was to identify and the characterize of RB1, CDKN2A and TP53 allele loss in ALL children patients at diagnosis. 46 children with de novo ALL were examined. Fluorescent in situ hybridization was performed on bone marrow smear preparations. We demonstrated that at least one of three investigated deletions occurred statistically more frequently in T-lineage leukemia patients (p = 0.044); this was the most frequent in respect to RB1 gene (p = 0.054). Additionally, at least one of the examined deletions was observed statistically more frequently in patients with WBC above 20 000/µl (p = 0.043), this was the most frequent for CDKN2A gene (p = 0.066). Presented results seem to give an evidence that deletions of RB1 and CDKN2A genes may contribute to the development of hyperleukocytic type of T-lineage ALL in children, nevertheless this observation needs further investigations.
    Polish journal of pathology: official journal of the Polish Society of Pathologists 01/2013; 64(2):121-8. · 0.49 Impact Factor
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    ABSTRACT: The pathogenesis of acute and chronic GvHD is not fully elucidated. The purpose of this model is to evaluate quantitatively the influence of the number of disparate HLA alleles and extended haplotypes on occurrence and severity of acute and chronic GvHD. N=604 donor recipient pairs transplanted in Polish centers in 2002-2012 were evaluated for staging and grading of acute and chronic GvHD and tested for HLA A, B, C, DRB1 and DQB1 alleles. The most probable haplotype pairs were inferred using PHASE software. For correlations polynominal regression model and ANOVA analyses were used. The correlation of the number of disparate HLA alleles (0 to 3) with the occurrence of GvHD was stronger for aGvHD than cGvHD (r=.099,p=.020 vs. r=.088, p=.065). The correlation between number of disparate alleles was even more pronounced for grade stratified aGvHD (0-IV), but not for extension stratified cGvHD (r=.121, p=.0052 vs. r=.090, p=.062). The respective correlations of the number of disparate HLA haplotypes (0-2) with aGvHD and cGvHD were as follows: for occurrence r=0.128, p=0.0029 vs. r=0.107, p=.026 and for grading r=0.156, p=.00030 vs. r=.079, p=.11. The pathways of HLA disparity inducing acute and chronic GvHD seem to be different. HLA molecule disparity level was correlated and haplotype disparity level was highly correlated with occurrence and grading of aGvHD. On the contrary, the data indicate that the number of disparate HLA molecules has limited influence on the occurrence of cGvHD. However, the number of disparate haplotypes significantly influenced the occurrence of cGvHD. The data point to peptide presentation repertoires rather than HLA molecule T cell recognition site sequence that may be of importance in cGvHD. Supported by National Center of Science, project No. N N402 351138.
    27th European Immunogenetics and Histocompatibility Conference, Maastricht, the Netherlands, May 11-14, 2013; 01/2013
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    ABSTRACT: In allogeneic hematopoietic stem cell transplantation (HSCT) settings the HLA typing gives only a partial information on the level of donor-recipient histocompatibility. The disparity of non-typed MHC loci can be incorporated in HLA disparate haplotypes due to their strong linkage disequilibrium with typed alleles. The aim of the study was to compare MHC haplotype (PHASE software) and HLA molecule disparities and their influence on the survival of HSC transplanted malignant patients. N=587 donor-recipient pairs were stratified for the number of disparate MHC A-C-B-DRB1-DQB1 haplotypes (0, 1 or 2) or the number of disparate HLA molecules (0, 1 or 2+3). Kaplan-Meyer survival curves were plotted and one year overall survival (OS) of 3 groups in each strata were compared using Chi2 test. When all N=587 donor-recipient pairs were stratified for the number of mismatched haplotypes (mmHp) or mismatched HLA molecules (mmHLA) their OS fit better to the number of mmHp than mmHLA (Chi2=7.64; p=0.022 and Chi2=6.39; p=0.041, respectively). This result was confirmed when comparison was restricted to N=495 patients diagnosed for malignant disease (Chi2=7.55; p=0.023 and Chi2=6.51; p=0.039, respectively). In non-malignant patients (N=92) neither mmHp nor mmHLA influenced OS (Z=0,40; p=0,69 and Chi2 =0,62; p=0,73). Interestingly, in malignant patients presenting standard risk disease phase during HSCT (N=372) the fit was insignificant for mmHLA and reached the statistically significant level for mmHp (Chi2=5.22; p=0.074 and Chi2=6.77; p=0.034, respectively). The number of disparate MHC haplotypes and HLA molecules are of vital importance for the survival of malignant patients with standard risk disease phase during HSCT. The disparate MHC haplotypes are more harmful than disparate HLA molecules and should be equally considered during HSC donor selection process for malignant patients. Supported by National Center of Science, project No. N N402 351138.
    27th European Immunogenetics and Histocompartibility Conference, Maastricht, the Netherlands, May 11-14, 2013; 01/2013
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    ABSTRACT: Single allele HLA disparity can sometimes be a result of a haplotype phase inversion and then both HLA haplotypes can be disparate. Haplotypic disparity is accompanied by the disparity of non-tested MHC components frequently remaining in linkage disequilibrium with known components. The aim of the study was to compare haplotype and HLA molecule disparities and their influence on the survival of hematopoietic stem cell transplanted (HSCT) patients. Transplanted in Polish centers in 2002-2012, N=587 donor-recipient pairs were stratified for the number of disparate HLA A-C-B-DRB1-DQB1 haplotypes (0, 1 or 2 disparate Hp) or the number of disparate HLA molecules (0, 1 or 2+3 disparate HLA). The most probable extended haplotype pairs were inferred using PHASE software. Kaplan-Meyer survival curves were plotted and one year overall survival (OS) of 3 groups were compared using Chi2 test, df.=2 and goodness of trend was compared between strata. When all N=587 donor-recipient pairs were stratified for the number of mismatched haplotypes (mmHp) or mismatched HLA molecules (mmHLA) their OS fit better to the number of mmHp than mmHLA (Chi2=7.64; p=0.022 and Chi2=6.39; p=0.041, respectively). The higher predictive power of mmHp than mmHLA was even more obvious when comparison was restricted to OS of N=457 patients presenting standard risk disease phase during transplantation (Chi2=7.86; p=0.019 and Chi2=6.34; p=0.042, respectively). The prediction of mmHp and mmHLA was not the case for N=97 patients presenting high risk disease phase during transplantation (Chi2=0.23; p=0.89 and Chi2=0.94; p=0.62, respectively). The number of disparate MHC haplotypes and HLA molecules are of vital importance for standard risk HSCT-recipients’ survival. The disparate MHC haplotypes are more harmful than disparate HLA molecules and should be equally considered during hematopoietic stem cell donor search/selection process. Supported by National Center of Science, project No. N N402 351138.
    27th European Immunogenetics and Histocompatibility Conference, Maastricht, the Netherlands, May 11-14, 2013; 01/2013
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    ABSTRACT: The polymorphism of 14-bp tandem repeat sequence located in the ASNS gene probably acts as a transcriptional enhancer element and leads to higher expression of the gene in carriers of more than 2 repeats (>R2). We searched for an association with disease outcome in 264 children with ALL. A multivariate proportional hazard regression model adjusted for age at diagnosis (HR (95%CI) = 1.05 (1.04–1.09)) and high-risk group (HR(95%CI) = 3.47 (1.74–6.88)) revealed that R3 carriers with a poor response at day 15 had an increased risk of events, HR (95%CI) = 2.72 (1.06–6.96). These results suggest a conditional interaction between the ASNS polymorphism and an early response to chemotherapy among pediatric patients with ALL.
    Leukemia research 01/2013; · 2.36 Impact Factor
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    ABSTRACT: ABSTRACT The total number of 817 ALL and 181 AML children were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, the impact on long-term response was showed for ITRT to thirteen drugs, while in initial AML only for cytarabine. For ALL patients, combined 5-drug ITRT profiles to prednisolone, L-asparaginase, vincristine, cytarabine and daunorubicin or doxorubicin had predictive value for pDFS in univariate analysis, whereas in multivariate analysis, bone marrow response by day 33 was the only prognostic factor. For AML patients, no factor had prognostic value for pDFS in univariate analysis, while ITRT to cytarabine almost reached significance. In conclusion, ITRT can be possibly regarded as a risk factor in childhood acute leukemias.
    Leukemia & lymphoma 10/2012; · 2.40 Impact Factor
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    ABSTRACT: T-cell acute lymphoblastic leukemia is a heterogeneous malignancy originating from developing lymphocyte precursors likely due to mutations in genes regulating thymocyte differentiation. Here, we characterized mutation status of BCL11B and FLT3 genes, presumably involved in T-ALL, together with FBXW7 and NOTCH1 as known players in T-ALL in 65 pediatric T-cell acute lymphoblastic leukemia patients. We also aimed at the assessment of prognostic value of NOTCH1 and FBXW7 mutations in ALL-IC BFM 2002 protocol. FLT3 and BCL11B mutations were detected in 3% and 2% of patients, respectively. FBXW7 mutations were observed in 8% of patients, while NOTCH1 was mutated in 40%. No correlation was found between NOTCH1 and FBXW7 mutations and traditionally used clinical factors or molecular features. In total we have detected nine mutations, which have not been previously described by others. Eight of them were found in NOTCH1 and one in BCL11B gene. Observed frequencies of NOTCH1 and FBXW7 are in line with previous reports, thus confirming postulated participation of these two genes in T-ALL pathomechanism. Moreover, we report on mutation frequency of FLT3 and BCL11B, not extensively studied in T-ALL so far. Finally, we suggest a putative role of BLC11B as an oncogene in T-ALL pathogenesis.
    Blood Cells Molecules and Diseases 10/2012; · 2.26 Impact Factor
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    ABSTRACT: NTRODUCTION: As Central Nervous System tumors account for second most common childhood malignancies, improving treatment modalities can lead to increase the survival rate of patients. The epidemiological investigations make a large-scale database of analysis for prognostic features of this group. In this study, we examined the epidemiology of childhood brain tumors in patients who referred to MPCTRC (one of the main national referral centers for childhood malignancies in Iran) for treatment. MATERIAL & METHOD: This cohort (simple sampling) study consisted of 198 children less than 15 years old with CNS tumor who referred to MPCTRC since 2007 to 2010. The unique checklist contained epidemiological features filled for each individual. Data analyzed by SPSS version 19 with Kolmogorov-Smirnov and Chi square tests. RESULTS: Out of enrolled patients 125(63.1%) male and 73(36.9%) female, had the mean age of 6.11 ± 3.65 years old. Tumors located in supratentorial (N = 60, 30.3%), infratentorial (N = 134, 67.7%) and spinal (N = 4, 2%). High-grade glioma and medulloblastoma were the most tumors in supratentorial and infratentorial locations respectively. The majority of patient's stage in medulloblastoma group was T2M0 (N = 44, 22.2%). The most clinical findings were vomiting, headache and impaired vision respectively. Thirty-one (15.7%) patients had relapse. there were 76(38.4%) off treatment and 82 (41.4%) death. The five years survival rate was 36%. CONCLUSION: According to the similar previously studies, the epidemiological features are same but the survival rate in this investigation was lower. Therefore, cautious interpretation in the future's investigations is undesirable. Brain tumor-based approach can lead to determine better treatment modalities for increasing cancer burden in pediatric malignancies.
    Neuro-Oncology. 06/2012; 14(suppl 1):i106-i110.

Publication Stats

469 Citations
205.78 Total Impact Points

Institutions

  • 2011–2013
    • University of Lodz
      Łódź, Łódź Voivodeship, Poland
  • 2003–2013
    • Medical University of Lublin
      • Department of Pediatric Hematology, Oncology and Transplantation
      Lyublin, Lublin Voivodeship, Poland
  • 2012
    • Poznan University of Medical Sciences
      • Clinic of Pediatric Oncology Hematology and Transplantology
      Posen, Greater Poland Voivodeship, Poland
  • 2005–2011
    • Jagiellonian University
      • Clinic of Pediatric Oncology and Hematology
      Cracovia, Lesser Poland Voivodeship, Poland
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 2009
    • Nicolaus Copernicus University
      • Department of Pediatrics Hematology and Oncology
      Toruń, Kujawsko-Pomorskie, Poland
  • 2005–2008
    • Lublin Oncology Center
      Lyublin, Lublin Voivodeship, Poland
  • 2007
    • Wroclaw Medical University
      Vrotslav, Lower Silesian Voivodeship, Poland
  • 2006
    • Children's Memorial Health Institute
      • Department of Medical Genetics
      Warsaw, Masovian Voivodeship, Poland
  • 2002
    • Szpital Uniwersytecki nr 1 im. A. Jurasza w Bydgoszczy
      Bromberg, Kujawsko-Pomorskie, Poland
  • 1999
    • Collegium Medicum of the Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland