Edita Kabickova - Academia.edu (original) (raw)

Papers by Edita Kabickova

Annals of Oncology, Sep 1, 2017

PubMed, Jan 18, 1999

Background: To determine the feasibility and results of treating children with non-Hodgkin's lymp... more Background: To determine the feasibility and results of treating children with non-Hodgkin's lymphomas (NHL) according to very intensive protocols based on the German Berlin Frankfurt Münster NHL 90 study. Methods and results: From 1991 until 1995 eighty two patients less than 18 years of age with NHL were admitted to our department. Sixty three of them were eligible for the study. The entire group consisted of 43 males and 20 females (ratio 2.1:1). Median age was 10 2/12 years. Eleven had stage I disease, 4 stage II, 29 stage III and 19 stage IV disease. Histologies represented were: large cell lymphoma 22, lymphoblastic lymphoma 19, and Burkitt lymphoma 10 patients. In 12 cases the immunophenotype was not further classified as to B-cell or T-cell subtype. Patients were stratified into the therapy groups "B" or "non B" according to histopathology, clinical stage and LDH level. Therapy for the B group consisted of 2, 4 or 6 courses of intensive 5 day pulses of 6 drugs. Patients in the non B group received the protocol for acute lymphoblastic leukemia including reinduction and CNS irradiation for advanced stages. At a median follow-up of 35 months the probability of event free survival (pEFS) at 5 years 70% and overall survival 73% for entire group. For therapy group B pEFS was 76%. The non B therapy group had a pEFS 60% (p = 0.22). There was a significantly better outcome for children classified as stage I and II. There was no statistical difference between stage III and IV. Treatment results were comparable between NHL subtypes, except for large cell lymphomas, which did significantly better (pEFS 90%). Conclusions: The use of protocols based on BFM 90 study in the Czech Republic was feasible. The pEFS are approximately 10% lower than the German study but comparable to some other studies. Outcome for large cell lymphomas was excellent. Reduction of treatment related complication and mortality rate as well as more precise classification are required.

European Journal of Cancer Care, Aug 4, 2015

Over 14,000 patients aged 15-24 are estimated to be diagnosed with cancer in the EU each year. Te... more Over 14,000 patients aged 15-24 are estimated to be diagnosed with cancer in the EU each year. Teenagers and Young Adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU FP7 European Network for Cancer Research in Children and Adolescents program (ENCCA) a specific European Network for Teenagers and Young Adults with Cancer (ENTYAC) has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and pediatric services to eliminate the gap in the management of TYA with cancer.

Journal of Clinical Oncology, Jul 1, 2010

The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been det... more The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL. Patients and Methods Patients younger than age 19 years with CD20 ϩ B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m 2 administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had Ն 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity. Results From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n ϭ 16), IT therapy in CNS-negative patients (n ϭ 8), corticosteroid treatment (n ϭ 3), technical inadequacy of response evaluation (n ϭ 21), or no evaluable lesion (n ϭ 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P ϭ .007). Conclusion Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.

Hematological Oncology, Jun 1, 2023

Andrologia, Oct 18, 2020

Curative therapy for cancer during childhood can adversely affect all aspects of male reproductiv... more Curative therapy for cancer during childhood can adversely affect all aspects of male reproductive health (Kenney et al., 2012; Romerius et al., 2011; Skinner et al., 2017). Many young adult cancer survivors still have uncertainty about their reproductive potential (Benedict et al., 2016), and this uncertainty can negatively affect their psychological well-being (Alexis et al., 2020). Male infertility studies in survivors are often based on self-reported questionnaire results (Wasilewski-Masker et al., 2014), and information about semen quality in cured cancer patients compared to a controlled population is limited (Jahnukainen et al., 2011; Thomson et al., 2002). According to previous studies, semen quality characteristics are highly variable even among men without cancer treatment (Cooper et al., 2010). Data regarding cancer treatment-related risk factors for impaired spermatogenesis vary between studies (Meistrich, 2013; Pacey et al., 2012). Irradiation of the gonads and/or the use of certain classes of chemotherapeutic agents (e.g. alkylating agents) may damage spermatogenesis, leading to aspermia or severe oligozoospermia (Green et al., 2014; Skinner et al., 2017). The reduction in sperm number is probably due to the direct cytotoxic effect of anticancer drugs

Leukemia, May 11, 2020

Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL)... more Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n ϭ 186), myelodysplastic syndrome (MDS; n ϭ 69), and nonmeningioma brain tumor (n ϭ 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% Ϯ 2.9%, 31.1% Ϯ 6.2%, and 18.3% Ϯ 3.8%, respectively). Five-year survival estimates for AML were 11.2% Ϯ 2.9% for 125 patients diagnosed before 2000 and 34.1% Ϯ 6.3% for 61 patients diagnosed after 2000 (P Ͻ .001); 5-year survival estimates for MDS were 17.1% Ϯ 6.4% (n ϭ 36) and 48.2% Ϯ 10.6% (n ϭ 33; P ϭ .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% Ϯ 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m 2 per week and mercaptopurine of at least 75 mg/m 2 per day. Myeloid malignancies with monosomy 7/5qϪ were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P ϭ .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts.

Blood, Jan 21, 2020

Initial high-risk disease, disease progression, not reaching CR before transplantation are risk f... more Initial high-risk disease, disease progression, not reaching CR before transplantation are risk factors in patients with relapsed BL/B-AL. l Time-condensed continuous infusion chemoimmunotherapy followed by stem cell transplantation forms the basis for future studies. Children with refractory or relapsed Burkitt lymphoma (BL) or Burkitt leukemia (B-AL) have a poor chance to survive. We describe characteristics, outcome, reinduction, and transplantation approaches and evaluate risk factors among children with progression of a BL/B-AL included in Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Münster studies between 1986 and 2016. Treatment recommendation was reinduction including rituximab from the early 2000s followed by blood stem cell transplantation. The 3-year survival of the 157 children was 18.5 6 3%. Survival significantly improved from 11 6 3% before to 27 6 5% after 2000 (P < .001), allowing for risk factor analyses among the latter 75 patients. Survival of 14 patients with relapse after initial therapy for low-risk disease (R1/R2) was 50 6 13% compared with 21 6 5% for 61 patients progressing after R3/R4 therapy (P < .02). A total of 25 of 28 patients with progression during first-line therapy, 31 of 32 with progression during reinduction, 15 of 16 not reaching a complete remission (CR) before transplantation, 9 of 10 treated with rituximab front-line, and all 13 patients not receiving rituximab during reinduction died. Forty-six patients received stem cell transplantation (20 autologous, 26 allogeneic). Survival after a regimen combining rituximab with continuous-infusion chemotherapy followed by allogeneic transplantation was 67 6 12% compared with 18 6 5% for all other regimen and transplantations (P 5 .003). Patients with relapsed BL/B-AL have a poor chance to survive after current effective frontline therapies. Progression during initial or reinduction chemotherapy and initial high-risk disease are risk factors in relapse. Time-condensed continuous-infusion reinduction followed by stem cell transplantation forms the basis for testing new drugs.

Social Science Research Network, 2022

$Research paper thumbnail of Clinical Characteristics and Outcome of Pediatric Patients with Relapsed or Refractory Hodgkin Lymphoma: Gazi University Pediatric Oncology Experience$

Klinische Pädiatrie, 2014

PubMed, Jul 1, 2011

Burkitt lymphoma (BL) is a well characterized entity. For atypical findings a term Burkitt-like l... more Burkitt lymphoma (BL) is a well characterized entity. For atypical findings a term Burkitt-like lymphoma (B-LL) was applied in the past, but the interpretation of the morphological appearances was subjective and poorly reproducible. We used a combined approach (morphology using classical histological staining; immunohistochemistry-IHC; fluorescence in situ hybridization-FISH on interphase nuclei; cytogenetics) to perform a retrospective study on 39 patients diagnosed as BL and B-LL at our department in the years 1982 to 2002. By FISH we demonstrated t(8;14)(q24;q32) in 31 patients; in further two we found a break at 8q24, suggestive of a variant translocation. In three patients with the cytogenetic investigation available we confirmed the findings of FISH--two lymphomas had the t(8;14)(q24;q32), one had t(2;8)(p12;q24). IHC showed CD20, CD10, BCL-6, p53 expression, and Ki-67 antigen in > 95% of the tumor cell population in a majority of the patients. There was a group of 4 patients in whom the t(8;14)(q24;q32) or a break at 8q24 were not found (FISH). These cases were reclassified within the WHO defined grey zone subgroup of B-cell lymphoma unclassifiable with features intermediate between diffuse large cell lymphoma (DLBCL) and Burkitt lymphoma--I-DLBCL/BL. Two further cases were reclassified as DLBCL based on a combined IHC and FISH findings. A lymphoma of one of these patients had breaks at 3q27 (BCL6) and at 14q32 (IGH) suggestive of t(3;14)(q27;q32). The overall survival estimate of 33 patients with the diagnosis of BL was 54%. Most of deaths occurred within 6 months after the tumor diagnosis. The unfavorable clinical outcome appears to be associated with a strong expression of the p53 protein in the tumor cell population. Individually utilized methods in the diagnosis of BL may lead to false diagnostic conclusions. A combined approach helps to establish a more reliable diagnosis of BL and to separate grey zone lymphomas I-DLBCL/BL and DLBCL with morphological mimics of BL to start adequate treatment. I-DLBCL/BL is a non-homogenous group of lymphomas necessitating further analysis in a prospective study.

Pathology Research and Practice, Mar 1, 2017

We report cytogenetic and molecular genetic analysis of a pediatric tumor positive for the CIC-DU... more We report cytogenetic and molecular genetic analysis of a pediatric tumor positive for the CIC-DUX4 fusion. The tumor belongs to a rare, diagnostically challenging subgroup of undifferentiated small round cell sarcomas. A balanced t(4;19)(q35;q13.1-2) was identified by G-banding, as a sole cytogenetic finding. The translocation was also identified by the M-FISH technique. After RT-PCR, the tumor sample was positive for the CIC-DUX4 fusion. The PCR product contains a novel, so far unreported variant of the CIC-DUX4 fusion transcript, with a fusion of the exon 20 from the CIC gene and the exon 1 from the DUX4 gene.

Genes, Chromosomes and Cancer, Jan 21, 2019

Rare cases of hematological precursor neoplasms fulfill the diagnostic criteria of mixed phenotyp... more Rare cases of hematological precursor neoplasms fulfill the diagnostic criteria of mixed phenotype acute leukemia (MPAL), characterized by expression patterns of at least two hematopoietic lineages, for which a highly aggressive behavior was reported. We present a series of 11 pediatric non-leukemic MPAL identified among 146 precursor lymphoblastic lymphomas included in the prospective trial Euro-LBL 02. Paraffin embedded biopsies of 10 cases were suitable for molecular analyses using OncoScan assay (n=7), fluorescence in situ hybridization (FISH) (n=7) or both (n=5). Except for one case with biallelic KMT2A (MLL) breaks, all cases analyzed by FISH lacked the most common translocations defining molecular subsets of lymphoblastic leukemia/lymphomas. Two non-leukemic B-myeloid MPALs showed the typical genomic profile of hyperdiploid precursor B-cell lymphoblastic leukemia with gains of chromosomes 4, 6, 10, 14, 18 and 21. One B-T MPAL showed typical aberrations of T-cell lymphoblastic lymphoma, such as copy number neutral loss of heterozygosity (CNN-LOH) at 9p targeting a 9p21.3 deletion of CDKN2A and 11q12.2-qter affecting the ATM gene. ATM was also mutated in a T-myeloid MPAL case with additional loss at 7q21.2-q36.3 and mutation of NRAS, two alterations common in myeloid disorders. No recurrent regions of CNN-LOH were observed. The outcome under treatment was good with all patients being alive in first complete remission after treatment according to a protocol for precursor lymphoblastic lymphoma (follow-up 3-10 years, median: 4.9 years). In summary, the present series of non-leukemic MPALs widely lacked recurrently reported translocations in lymphoid/myeloid neoplasias and showed heterogeneous spectrum of chromosomal imbalances.

Cancer genetics and cytogenetics, Oct 1, 2006

We report a case of primary mediastinal (thymic) large B-cell lymphoma (PMBL) with an initial kar... more We report a case of primary mediastinal (thymic) large B-cell lymphoma (PMBL) with an initial karyotype containing numerical chromosomal aberrations: +X, +9, +12, +21, and a novel translocation t(2;11)(q?31; q23 approximately 24) with a duplication of the derivative chromosome 11. Subsequent multicolor fluorescence in situ hybridization (M-FISH) analysis revealed a der(14)t(8;14)(q24;q32). Further analysis using fluorescence in situ hybridization (FISH) with locus-specific probes revealed loss of the entire IgH locus from the der(14)t(8;14) and relocation of MYC to this derivative chromosome 14. Our data show definitively the existence of the t(8;14) in PMBL, previously only suspected. This finding supplies additional evidence that a translocation-mediated MYC activation may be an important event in the pathogenesis of this unique lymphoma.

Leukemia Research, 2008

Anaplastic large cell lymphoma (ALCL) represents a heterogeneous group of malignant lymphoprolife... more Anaplastic large cell lymphoma (ALCL) represents a heterogeneous group of malignant lymphoproliferative diseases with a consistent expression of the cytokine receptor CD30. ALCL is frequently associated with a NPM/ALK fusion gene which is found in up to 75% of pediatric ALCLs. Real-time quantitative RT-PCR (RQ-RT-PCR) of NPM/ALK and CD30 gene expression was employed to analyze minimal residual disease (MRD) in 10 patients with NPM/ALK positive ALCL in 79 follow-up bone marrow (BM) and/or peripheral blood (PB) samples. In all BM samples from relapses and/or closely before a relapse, BM samples revealed NPM/ALK and CD30 positivity in at least one of the iliac BM trephines. Five out of nine relapses were preceded or were accompanied by minimally half log increased NPM/ALK levels in the BM. We found that RQ-RT-PCR of the CD30 expression is not suitable for MRD detection--only two relapses were accompanied by an increase of the CD30 level above a level which was detected in BM/PB samples from healthy individuals. RQ-RT-PCR of NPM/ALK expression is a promising and rapid approach for monitoring MRD.

Annals of Hematology, Jun 7, 2016

Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome a... more Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified * K. Mellgren

Annals of Hematology, May 12, 2013

Haematologica, Aug 11, 2016

C hildren and adolescents with pre-existing conditions such as DNA repair defects or other primar... more C hildren and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, largescale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mis