Gunduz Gedikoglu

Oxidative DNA base damage and antioxidant enzyme levels in childhood acute lymphoblastic leukemia

We have investigated the levels of several antioxidant enzymes and the level of oxidative DNA base damage in lymphocytes of children with acute lymphoblastic leukemia (ALL) and in disease‐free children. Children with ALL had just been diagnosed with the disease and had received no therapy prior to obtaining blood samples. A multitude of typical hydroxyl radical‐induced base lesions in lymphocyte DNA of children were identified and quantified by gas chromatography‐isotope dilution mass spectrometry. Higher levels of DNA base lesions were observed in patients with ALL than in children without the disease. The levels of the antioxidant enzymes glutathione peroxidase, catalase and superoxide dismutase in lymphocytes of ALL patients were lower than in lymphocytes of controls. These findings are in agreement with earlier observations in various types of adulthood cancer. Some of the identified DNA base lesions are known to possess premutagenic properties and may play a role in carcinogenesis. The results may indicate a possible link between decreased activities of antioxidant enzymes and increased levels of DNA base lesions due to oxidative damage, and support the notion that free radical reactions may be increased in malignant cells.

Allogeneic versus autologous versus peripheral stem cell transplantation in CR1 pediatric AML patients: a single center experience.

Treatment of childhood acute myelocytic leukemia (AML) in first remission, is still evolving. Allogeneic bone marrow transplantation (BMT) in patients with a donor has been well established, but the role of autologous transplantation remains of interest, particularly in the light of some encouraging results in adults.

Prognostic significance of the TEL-AML1 fusion gene in pediatric acute lymphoblastic leukemia in Turkey

Purpose The t(12;21) translocation is the most common reciprocal chromosomal rearrangement in pediatric acute lymphoblastic leukemia (ALL). This translocation fuses two genes, TEL and AML1, and results in the production of the TEL-AML1 fusion protein. The authors investigated the incidence and prognostic significance of the TEL-AML1 fusion gene in patients with ALL in Turkey. Methods The authors analyzed 219 children with ALL using the reverse transcription–polymerase chain reaction. Results The TEL-AML1 fusion transcript was detected in 20.1% (44/219) of newly diagnosed children with ALL. TEL-AML1-positive patients had precursor B-cell ALL and were 3 to 10 years old at diagnosis. TEL-AML1-positive patients had a significantly lower rate of relapse compared with TEL-AML1-negative patients. TEL-AML1-positive patients have a higher overall survival rate than TEL-AML1-negative patients. Conclusions These data support that the presence of TEL-AML1 at diagnosis is an independent favorable prognostic indicator in patients with ALL in Turkey.

Is AML1/ETO gene expression a good prognostic factor in pediatric acute myeloblastic leukemia?

To assess the clinical significance of AML1/ETO gene detected by nested reverse transcriptase polymerase chain reaction, the outcome of 7 patients with acute myeloblastic leukemia between 3 and 14 years of age were presented. All patients had complete remission (CR) at the end of induction (AMLMRC 10 protocol) and 4 underwent unpurged autologous, 2 allogeneic (from matced siblings) non-T-cell-depleted bone marrow transplantations (BMT) in first CR. One patient died due to allogeneic BMT-related complications, and 4 patients relapsed at 13, 17, 18, and 26 months. Only one patient achieved second CR. All relapsed patients died between 18 and 36 months with resistant disease (n = 3) or infection during salvage chemotherapy (n = 1). Two patients who had autologous BMT are alive and disease free at 44 and 50 months. Although statistical significance could not be shown, event-free survival and overall survival rates of AML1/ETO-positive patients (28.57 and 28.57% , respectively) at 3.5 years were even lower than those of AML1/ETO-negative patients. The results confirm some previous reports that AML1/ETO gene in children and adolescents is not a favorable prognostic factor.

Reactivation: A severe problem in familial hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder with principal clinical features of fever and splenomegaly accompanied by pancytopenia, hypertriglyceridemia and/or hypofibrinogenemia with histological evidence of hemophagocytosis.1 Familial hemophagocytic lymphohistiocytosis (FHLH) shows an autosomal recessive mode of inheritance. When there is evidence of concurrent infection, the disease is often called infection-associated hemophagocytic lymphohistiocytosis (IAHS). The onset of FHLH and bouts of the disease may also be triggered by infections.2 We report our experience with six FHLH patients over a 2-year period that focuses on the variability of clinical features, overlap between familial and sporadic cases and the problem of reactivation.

MTT Assay for Drug Resistance in Childhood Acute Leukemia and Effect of Cyclosporin and Interferon

Cellular drug resistance is thought to be an important cause of the poor prognosis in childhood leukemia.4 Drug resistance in leukemic cells may occur primary or may be acquired. To develop more effective treatment regimens for resistance patients is necessary, but it is difficult to use many drugs at same time in patients.2,3 Therefore, it is more easy to use in vitro systems for various drug treatment of cells so that individual chemotherapy may be designed.3 A rapid colorimetric assay based on the ability of viable cells to reduce a tetrazolium-based compound (MTT) to a blue formazan product is an increasingly used assay for testing in vitro chemosensitivity of leukemic samples.2,3,4,5,7,8 MTT assay provides a good correlation between in vitro resistance to cytotoxic drugs and prognosis in childhood leukemia.1

SUCCESSFULL TREATMENT OF CHILDHOOD REFRACTORY CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA WITH CYCLOSPORINE A 168

SUCCESSFULL TREATMENT OF CHILDHOOD REFRACTORY CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA WITH CYCLOSPORINE A 168

HEPATIC ABNORMALITIES IN THALASEMIA MAJOR 83

Hepatic abnormalities of Thalasemic patients due to iron overload and hepatotropic viruses were evaluated. The study was undertaken between October 1993 and October 1994 in 29 patients (12 boys, 17 girls) with a median age of 13 years (range 3-22 years). Patients were transfused regularly to maintain a hemoglobin value of 10 g/dl or higher. All except a 3 year old girl were on subcutan desferroxamin therapy (40-60 mg/kg/day, 5 days/week). 62% of patients were splenectomised. Seropositivity was 82.76% for Hepatitis B virus 68.9% anti-HBs positive, 3.5% chronic HBsAg carrier) whereas 27.5% for Hepatitis C virus. In anti-HCV (+) group serum ALT levels were higher than anti-HCV(-) group, 114.75±67.75 and 67.61± 46.95, respectively (p:0.042). Mean serum ferritin level was 7145.13± 4938.75 ng/ml (range 224-20.000) and had a positive correlation with age, total number of transfusions, serum AST, ALT and total bilirubin but no correlation with GGT, D.Bilirubin, Alkaline phosphatase, PT, PTT, iron and iron binding capacity. 10 patients underwent liver biopsy. Biopsies revealed 1 inactive cirrhosis, 1 chronic persistant hepatitis, 4 portal fibrosis and hemochromatosis in all specimen. As a conclusion, Hepatitis B seropositivity is high among Thalasemic children. Iron chelating agent is efficient but can not prevent iron overload and liver damage completely. We recommend early vaccination of all Thalasemic children for Hepatitis B and screening of blood donors with more sensitive methods.