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Csongor Kiss

Publications and source records attributed to Csongor Kiss.

At least 19 recordsLinked to original sources
PubMed2007

Long-lasting partial remission by Interferon-alpha treatment in a child with essential thrombocythemia.

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained thrombocytosis, isolated hyperplasia of megakaryocytic lineage, and association with thrombotic or bleeding episodes. It is extremely rare in childhood and frequently presents without evident clinical signs. We describe a 3-year-old girl with severe headache and dizziness suffering from ET, who was treated with Interferon-alpha-2a (IFN) based on the potent effect of this agent to inhibit myeloid colonies induced by phytohemagglutinin A stimulated leukocyte conditioned medium (PHA-LCM). Bone-marrow-derived mononuclear cells of this patient did not exhibit spontaneous colony formation but responded to recombinant human (rh) erythropoietin (EPO), rh granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, and stem-cell factor in addition to PHA-LCM. After 65 months of in vivo IFN treatment, the patient experienced a sustained partial remission with platelet counts varying between 400 and 600 x 10(3)/microl.

Bone Marrow Examination↗
PubMed2006

Significance of oral Candida infections in children with cancer.

Candidiasis is common in children with cancer, particularly during periods of severe immunosuppression and neutropenia. Our aim was to study the microbiological changes in the oral cavity of children with newly diagnosed cancer. The study group consisted of 30 consecutive children and adolescents, 16 with acute lymphoblastic leukemia and 14 with solid tumors. Oral cultures to detect fungi and bacteria were conducted for all patients before treatment, during and after neutropenic episodes. In 23 patients developing fever simultaneous throat, urine and blood sampling was carried out. No pathogens were found in the cultures taken before the outset (30 cultures) or after recovery from (30 cultures) the neutropenic episodes. In the 45 oral cultures taken during the neutropenic episodes 38 (84.4%) proved positive. Fungi were the most frequently isolated oral pathogens: 33/38 yeast and 6/38 bacterial infections were identified. There was no association between the underlying malignancy and the occurrence of the positive cultures. Of the 30 patients, all 23 (76.7%) who have developed moderate-to-severe neutropenia, developed oral fungal colonization or clinically obvious fungal infection at least on one occasion during the study. In addition to oral samples, fungi were identified in 9/23 pharyngeal swabs, 6/23 urine and 1/23 blood cultures. The initial fungal pathogen was exclusively (33/33) Candida albicans. In extended severe neutropenic states, C. albicans was replaced by non-albicans species (C. kefyr, C. lusitaniae, C. sake, C. tropicalis) in 5 patients between 4 to 6 days of the neutropenic episodes. Four of the nonalbicans Candida strains were resistant to azole-type antifungal agents. Neutropenic episodes of children with cancer are associated with an increased risk of developing oral and even systemic infections with C. albicans that can be replaced by azole-resistant nonalbicans strains in prolonged neutropenia contributing to morbidity of these patients.

Adolescent↗
PubMed2006

Differential regulation of umbilical cord blood and leukemic B cells by interferon-alpha (IFN-alpha): observations in cultured cells.

The exact mechanism of the beneficial therapeutic action of interferon-a (IFN-alpha) in B-cell-lineage malignancies has not been adequately explained. Here we report on the differential effect of IFN-alpha2b on non-malignant B cells of umbilical cord blood and leukemic B-cell lines JY, BL-41 and BCBL-1. Leukemic cell proliferation was characterized by colony assay, whereas apoptosis was investigated by flow cytometry of propidium iodide-stained cells. The degree of differentiation was evaluated by measuring the expression level of Fcgamma receptor-II (FcgammaRII) labeled with anti-CD32-FITC monoclonal antibody using flow cytometry. IFN-alpha protected umbilical cord blood CD19-positive B lymphocytes from apoptotic cell death in vitro. IFN-alpha significantly decreased colony formation of all three cell lines, and in contrast to normal cells, induced apoptosis in JY and BL-41 and excessive necrosis in HHV-8 infected BCBL-1 cells. FcgammaRII was upregulated both in normal and in leukemic B cells as indicated by an increase both in the proportion of CD32-positive cells and the mean fluorescence intensity. From our results it seems that antiproliferative, apoptotic and differentiative effects of IFN-alpha are interrelated but distinct cellular events, which are differentially regulated in normal, leukemic and virus-infected cells of the B-cell lineage.

Apoptosis↗
PubMed2006

Combined local treatment and chemotherapy in the management of bilateral retinoblastomas in Hungary.

This retrospective study supports that brachytherapy combined with cytostatic therapy may effectively contribute to tumor control. The second eye of 13 patients with bilateral retinoblastoma was treated with plaque brachytherapy after the enucleation of the first eye. Eleven patients received systemic cytostatic therapy. The mean follow up was 60 (+/-42 SD) months. Twelve patients are alive and free of tumor, 8 of them with acceptable visual acuity. After cytostatic therapy, late nephropathy was observed in 2 patients. In conclusion, brachytherapy combined with cytostatic therapy will be an option in the management of bilateral retinoblastoma after the enucleation of the first eye.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A.

Blood coagulation factor XIII (FXIII) is a protransglutaminase circulating as a tetramer formed by two types of subunits (A2B2). The intracellular dimeric form of FXIII (A2) is present in platelets, megakaryocytes, monocytes and macrophages and has been detected in mono- and megakaryocytic leukemias. The aim of our study was to investigate FXIII-A expression in newly diagnosed B cell acute lymphoblastic leukemia (ALL) samples. We examined 47 de novo ALL cases of B cell origin by triple color labeling with flow cytometry. FXIII-A was detected by a FITC conjugated monoclonal antibody combined with CD34 and CD45 staining. In selected cases FXIII-A was investigated on slides prepared from blasts and visualized with a fluorescent microscope. In addition, blasts were studied by Western blot analysis and FXIII-A was measured by a highly sensitive ELISA method. By flow cytometry 19 samples of the 47 cases were found to be FXIII-A positive. Antigen concentration was 3.11 +/- 1.19 fg/blast, while normal lymphoid precursors and mature lymphocytes from B-CLL did not contain FXIII-A. In the lysate of lymphoblasts that were positive by flow cytometry, a single band (82 kDa) corresponding to FXIII-A was detected on Western blots. Confocal laser scanning microscopic examination revealed the presence of FXIII-A in the cytoplasm of these lymphoblasts. This novel expression site of FXIII-A in leukemic lymphoblasts can be utilized as a diagnostic tool and may also gain functional significance in B-lineage ALL.

Adolescent↗
PubMed2005

[Treatment results with ALL-BFM-95 protocol in children with acute lymphoblastic leukemia in Hungary].

BACKGROUND: In Hungary children (from 1 to 18 years of age) with de novo acute lymphoblastic leukemia were treated from January 1996 to October 2002, according to protocol ALL-BFM-95. AIM: The aim of this study was to evaluate the experience with this protocol, the treatment results according to the risk groups and to compare the Hungarian data with the international results. METHODS: Patients were stratified into 3 risk groups, based on initial white blood cell count, age, immunology, cytogenetics and response to treatment: standard, medium and high risk group. RESULTS: Three hundred sixty eight children entered the study (male-female ratio was 1.27:1, median age 6 years and 4 months). 110 (29.9%) children were in the standard, 210 (57.1%) in the medium and 48 (13%) in the high risk group. Duration of the chemotherapy was 2 years, except of the boys in the standard risk group, their maintenance therapy was 1 year longer. The overall complete remission rate was 93.2%. 20 (5.4%) children died in induction and 5 (1.4%) were non-responders. The 5-year overall survival for all patients was 78.5%, in the standard risk group 93.2%, in the medium risk group 78.4% and in the high risk group 44.5% with a minimum follow up of 1.19 years and median follow up of 4.85 years. From the 368 patients 272 (73.9%) are still in their first complete clinical remission and other 18 children are alive after relapse. In 14.7% of the patients relapse was diagnosed; the most common site was the bone marrow. In one patient second malignancy occurred. The 5-year event free survival for all patients was 72.6%, in the standard risk group 87.6%, in the medium risk group 72.1% and in the high risk group 39.9%. CONCLUSION: The treatment outcome of children with acute lymphoblastic leukemia improved remarkably over the last decades. 78% of children suffering from acute lymphoblastic leukemia could be cured with the ALL-BFM-95 protocol. The Hungarian results are comparable to those achieved by other leukaemia study groups in the world regarding the ALL-BFM-95 protocol.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Polymorphism of angiotensin converting enzyme is associated with severe circulatory compromise in febrile neutropenic children with cancer.

Angiotensin converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism influences the outcome of a number of cardiovascular diseases. ACE I/D polymorphism was investigated by PCR in 207 pediatric cancer patients and 144 controls. ACE I/D distribution of patients and controls was similar. The frequency of the D allele and the prevalence of the deletion (DD) genotype were significantly (P < 0.05) higher among patients with severe circulatory compromise requiring treatment in the intensive care unit (ICU) than among the other patients and controls. Patients with the DD and ID genotypes spent significantly (P < 0.05) longer time in the ICU than patients with the II genotype.

Adolescent↗
PubMed2005

A novel homozygous mutation (1619delC) in GPIIb gene associated with Glanzmann thrombasthenia, the decay of GPIIb-mRNA and the synthesis of a truncated GPIIb unable to form complex with GPIIIa.

The absence of agonist-induced platelet aggregation and the lack of fibrinogen receptor (GPIIb/IIIa) on the platelet surface demonstrated that the severe hemorrhagic complications of a child of Romany descent were caused by Glanzmann thrombasthenia. DNA sequencing revealed a novel homozygous deletion of a cytosine (1619delC) in the GPIIb gene causing a frameshift and predicting a novel stop codon at position 533 following 24 altered amino acids. Both parents possessed the same deletion in heterozygous form. The amount of GPIIb mRNA in the patient's platelets was 0.06% of the amount measured in control platelets. Neither GPIIb nor its truncated form could be detected in the platelets of the patient by Western blotting, while a small amount of GPIIIa was demonstrated. Quantitative flowcytometric analysis showed an elevated number of vitronectin receptors, a component of which is GPIIIa, on the patient's platelets. The surface expression of vitronectin receptor on thrombasthenic, but not on normal platelets was further increased by activation with thrombin receptor agonist peptide. BHK cells transfected with wild type GPIIIa andmutated GPIIb failed to express any mature GPIIb or pro-GPIIb. Immunoprecipitation with a polyclonal antibody recognizing both GPIIb and GPIIIa recovered a 60 kDa truncated form of GPIIb. This band was absent when immunoprecipitation was carried out with an antibody recognizing GPIIIa, suggesting that the truncated protein, lacking calf-1, calf-2 domains and major part of the thigh domain, is unable to form complex with GPIIIa.

Animals↗
PubMed2005

Coagulation factor XIII-A. A flow cytometric intracellular marker in the classification of acute myeloid leukemias.

The association of coagulation factors with leukocytes have been demonstrated in several previous studies. This study was designed to study the sensitivity and specificity of factor XIII subunit A (FXIII-A) labelling in cultured myeloblastic and monoblastic cell lines and to investigate the intracytoplasmic expression of FXIII-A in de novo acute myeloid leukemia (AML) samples. Myeloblastic and a monoblastic cell lines were cultured and investigated for lineage specific maturation markers and FXIII-A expression. Furthermore, FXIII-A expression was investigated in 12 normal samples (7 bone marrow and 5 peripheral blood), 86 de novo AML samples and 6 chronic myelomonocytic leukemia (CMML) samples. In the monoblastic MonoMac6 cell line the appearance of FXIII-A preceded that of CD14 while it remained negative in the myeloblastic PLB-985 cell line throughout its maturation period. Among the AML samples the average frequency of FXIII-A positive cells in myeloblastic leukemia samples was below 10%, while in M4 and M5AML samples it was above 50% and was significantly higher than the generally used CD14 marker (p < 0.0001). In the AML M4 and M5 cases, FXIII-A proved sensitive for the identification of monoblasts. FXIII-A can be considered as a reliable intracytoplasmic marker for the monocytic and megakaryocytic series and its presence is highly predictive for mono- and megakaryocytic AML and for CMML.

Antibodies, Monoclonal↗
PubMed2004

Cystatin C is a suitable marker of glomerular function in children with cancer.

Antineoplastic chemotherapy is associated with nephrotoxic side effects. Data on nephrotoxicity in childhood cancer are scanty, in part because of the difficulties in obtaining reliable markers of glomerular function. We used serum cystatin C (cysC) to assess glomerular function. CysC was compared with serum creatinine concentration (S(Cr)), the endogenous creatinine clearence ( C(Cr)), and the calculated Counahan formula ( C(Counahan)) in children with leukemia and solid tumors. CysC was measured by particle-enhanced immunoturbidimetric assay. Serum and urinary creatinine concentrations were determined by the Jaffé method. Samples were obtained from 258 children, including 92 receiving anticancer chemotherapy, 108 long-term survivors, 40 children without any renal disease, and 18 patients with chronic renal insufficiency. CysC of patients on current chemotherapy was assessed both before and after treatment. Significant correlations were found between cysC and S(Cr) and between 1/cysC and C( Counahan). CysC increased significantly after cisplatin, methotrexate, cyclophosphamide, ifosfamide, and multimodality treatment. Our results suggest that cysC measurement can be used to characterize glomerular function in children with cancer.

Adolescent↗
PubMed2004

[Cervical neuroblastoma in an infant].

The case of a one-month-old patient admitted to the Department of Pediatrics (Medical and Health Science Center, Debrecen University) because of respiratory distress caused by a cervical mass compressing the upper respiratory pathways is presented. The mass could only be partially removed, the histological diagnosis proved to be neuroblastoma (SBCT: "small blue cell tumor"). Despite the fact that the DNA index of tumor cells (ploidy measurements) and the age of the patient suggested a favourable prognosis, the tumor continued to grow and metastases appeared. Because of symptoms of compression exerted on the respiratory system by the tumor, chemotherapy had to be applied. Since a standard OPEC/OJEC chemotherapeutic protocol proved to be not entirely effective and a residual tumor was still present, retinoic acid and interferon treatment was introduced. Presently, 4 years after the diagnosis, the patient is in complete remission and can be considered to be cured. The case presented here demonstrates that despite the favorable prognosis of the majority of infant neuroblastomas, in some cases the anatomic location of the tumor, leading to disturbance of vital functions, may serve as indication of chemotherapy. Our experience also proved the efficacy of retinoic acid and interferon treatment in relapsed neuroblastoma.

Biomarkers, Tumor↗
PubMed2004

Leukemic cells and the cytokine patchwork.

BACKGROUND: In leukemia, the clonal population is characterized by a hierarchical organization. Although the majority of the leukemic population is generated after post-determinic divisions, a subset of cells retain undifferentiated "blast" morphology. In addition, leukemic cells often have numerical or structural chromosomal abnormalities, aberrant gene expression patterns, and abnormal cell surface marker profiles. Despite these differences when compared to normal bone marrow and blood cells, leukemic cell survival and proliferation, just like that of normal progenitor cells, is influenced by hematopoietic growth factors. A major issue is whether differential regulation of normal and leukemic hematopoietic cells by cytokines can be exploited in antileukemic treatment or, in contrast, whether in vivo cytokine therapy may even be harmful to the patients. PROCEDURE: Here we review the results of recent experimental and clinical observations that investigated the influence of cytokines on leukemic cell growth and differentiation in vitro and in vivo. RESULTS: The majority of studies indicate that hematopoietic growth factors are involved in the regulation of proliferation and terminal differentiation of leukemic blast cells. Genetic aberrations involving cytokines or their receptors may contribute to leukemogenesis. Abundant interactions, cross-lineage stimulation, and aberrant response patterns seem to transform the complex cytokine network regulation of normal hematopoiesis into an even more interlaced "patchwork" that controls leukemic hematopoiesis. CONCLUSIONS: Since hematopoietic growth factors are present in high serum concentrations in patients with acute leukemia and myelodysplastic syndromes, consequences of possible interactions should be kept in mind even when well-defined human recombinant factors in single application are to be involved in antileukemic protocols.

Animals↗
PubMed2004

Late effects on renal glomerular and tubular function in childhood cancer survivors.

BACKGROUND: Late nephrotoxicity among childhood cancer survivors is poorly documented. METHODS: We investigated 115 patients and 86 controls assessing serum cystatin C concentration (CysC), urinary N-acetyl-beta-D-glucosaminidase activity (NAG), and microalbuminuria. Proteinuria was quantified and electrophoresis performed. Polymorphism of the angiotensin convertase enzyme (ACE) gene was determined by genomic PCR. RESULTS: CysC was elevated in Wilms tumor (WT) patients. Gross proteinuria was observed in 30 patients including three patients with progressive proteinuria who improved on ACE-inhibitor treatment. Neither patients with proteinuria nor the entire study population differed from controls with respect to ACE polymorphism. Pathologically elevated urinary NAG was noted in 38% of leukemia/lymphoma, 54% of solid tumor, 20% of WT survivors. A similar distribution of pathological microalbuminuria was found. CONCLUSIONS: Mild-to-moderate subclinical glomerular and tubular damage can be identified in many childhood cancer survivors. However, most patients experience some spontaneous recovery from acute nephrotoxicity.

Adolescent↗