The Langerhans cell histiocytosis (LCH) in children is relatively rare and the long-term analysis of therapy results has not been done yet in Hungary. The aim of this study was to investigate the incidence, clinical features, prognostic risk factors, and treatment results of children's LCH in Hungary in a 20-year period. Children less than 18 years of age with newly diagnosed LCH in Hungary were entered in this study. Clinical data of all children with LCH were reported to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The clinical files were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. Median follow-up duration of surviving patients is 10.98 years. Between January 1981 and December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The annual incidence of LCH in children younger than 18 years of age was 2.24/million children. The male-female ratio was 1.36:1; the mean age was 4 years 11 months. Thirty-eight children had localized disease and in 73 cases systemic dissemination was found already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation, and 5 children got only local irradiation. In 2 cases remission was achieved with local steroid administration. Seventy-five patients received chemotherapy. In the 20 years of the study 14 children died, 9 due to the progression of the disease. Sixteen patients had relapse with a mean of 2.16 +/- 1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n = 111) was 88.3 +/- 3.1% at 5 years and 87.3 +/- 3.2% at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.

A 2-year-old girl presented with thrombocytopenic purpura. Clinical examination and follow-up documented severe bone marrow hypoplasia associated with bilateral progressive Coats retinopathy, nail dystrophy, fine hair, and apparent chromosome instability. The syndrome is regarded as a variant of the Révész syndrome sharing some findings of dyskeratosis congenita.

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To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin's lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 micromol/L to 58 micromol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma.

To determine the mortality and survival rates, side effects of surgery and adjuvant chemo- and radiotherapy, somatic development, and fertility, the data of 142 patients under the age of 1 year operated upon for solid malignant tumors from 1975 through 1983 were analyzed. The follow-up period ranged from 16 to 25 years (mean 20); 79 patients survived. The male/female ratio of the survivors was 51/28. Investigations were based on the Hungarian Tumor Registry, personal interviews with the patients and their parents, and detailed questionnaires. Fifty-one patients died, 44 of them before the age of 3 years; 13 were lost to follow-up. Of the 79 survivors, 48 had abdominal and 31 extra-abdominal tumors (35 neuroblastomas, 21 renal tumors, 15 soft-tissue sarcomas, 5 gonadal tumors, 2 sacrococcygeal carcinomas, 1 hepatic tumor). Side effects of surgical intervention included partial urinary incontinence (2), partial fecal incontinence (1), intestinal obstruction (2), nerve injury (1), thorax deformity (4), and scar formation resulting in psychological problems (12). Chemotherapy alone (41 patients) resulted in side effects in 19 patients, radio- and chemotherapy in combination (23) caused side effects in 20. Fifteen patients did not receive adjuvant therapy. The most serious late side effects were 24 spinal deformities, one-half of them severe, breast underdevelopment, muscular deformity, and renal damage. In 19 patients more then one side effect was detected. Height and weight gain decreased ( P < 0.01 and <0.05, respectively) in the first 8-10 years of follow-up and accelerated significantly ( P < 0.05 and <0.05, respectively) in the second half of follow-up. The short follow-up time (16-25 years) permitted only limited analysis of infertility. Whenever possible, surgical excision should be the treatment of choice. No routine aggressive chemotherapy is indicated. Radiation therapy, which frequently results in long-term musculoskeletal morbidity, should be avoided. Catch-up somatic development occurred in the second part of the follow-up period.

The prevalence of 55 well-defined mild errors of morphogenesis (MEMs) was determined in 100 children with acute lymphoblastic leukemia (ALL), their 80 sibs, 91 mothers, and 76 fathers. Seventy-four patients were treated in Pécs (Hungary) and 26 in Tübingen (Germany). Only white Caucasian index cases were included in the study. Two-hundred children examined for acute infections served as controls. In addition, we analyzed the family history for birth defects and malignancies, associated major malformations, birth weight, birth order, and pretreatment height of the patients. The results of the Pécs and Tübingen patients were at first evaluated separately but since no differences were found only the cumulative data were analyzed further. A significantly increased prevalence of MEMs was found in the ALL patients and their sibs of both sexes: their MEM/subject ratios were 1.59 and 1.51, respectively, whereas the same parameter was 0.74 in the mothers, 0.67 in the fathers and 0.69 in the controls. The same tendency was observed when familial cases and/or age-dependent MEMs were excluded and when malformation-type and variant-type MEMs were evaluated separately. No association of ALL with specific MEMs or combinations was recorded. Family history, associated major malformations, parity and birth weight of the patients did not differ significantly from the local reference values, whereas the pretreatment height of the male probands proved to be greater than expected.

The aim of this study was to investigate seasonal trends in the incidence of acute lymphoblastic leukaemia (ALL) around the times of birth and diagnosis in children aged 0-4 years and also to examine gender specific effects. Children born in South Hungary during 1981-1997 were analysed. Registrations of first malignancies for children, diagnosed under age 5 years before the end of 2002 were obtained from the Hungarian Paediatric Oncology Group providing a representative sample of Hungarian children over a 17 year period of time. Data were available on the corresponding numbers of births for each month of the study period were obtained. Statistical analyses were performed using logistic regression with harmonic components. The study analysed 121 cases of children, aged under 5 years, who were diagnosed with ALL. We found no seasonal effect related to date of diagnosis. However, there was seasonal variability for ALL related to date of birth. Maximal rates were seen in children born in February and August in the simple harmonic regression model for all children diagnosed with ALL. Analysis by gender found evidence of seasonality related to month of birth with peaks in February and August in boys, but different seasonal effects were seen for girls (peak in November, nadir in May). Our study provides some evidence that male specific immune responses to infections around the time of birth could explain the male predominance in the incidence of ALL.

BACKGROUND Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma (Schwannian stroma–poor) category, the authors histologically identified a group of rare tumors, known as large cell neuroblastomas (LCNs), that are composed of large cells with sharply outlined nuclear membranes and 1–4 prominent nucleoli. METHODS Histologic and immunohistochemical features of LCN were characterized. Morphologic characteristics, clinical features, and MYCN status were compared between LCNs and conventional neuroblastomas documented in the files of two European centers (the Sir James Spence Institute of Child Health, Royal Victoria Infirmary, University of Newcastle, Newcastle upon Tyne, United Kingdom, and the Medical and Health Sciences Center, University of Pécs, Pécs, Hungary). RESULTS Of 92 peripheral neuroblastic tumors (pNTs; including neuroblastoma [n = 81]; ganglioneuroblastoma, intermixed [n = 6]; and ganglioneuroblastoma, nodular [n = 5]), 7 (7.6%) qualified as LCN. All 7 LCNs were classified as having unfavorable histology (UH) according to the International Neuroblastoma Pathology Classification. The LCNs were composed of monomorphous undifferentiated neuroblasts and shared certain histologic features, such as a high incidence of high mitosis‐karyorrhexis index and a low incidence of calcification, with other neuroblastomas in the conventional UH (c‐UH) group. These features were significantly different from those of neuroblastomas in the conventional favorable histology (c‐FH) group. On immunohistochemical analysis, LCN tumor cells were positive for neuron‐specific enolase (5 of 5 cases), protein gene product 9.5 (5 of 5 cases), synaptophysin (5 of 5 cases), tyrosine hydroxylase (focally in 3 of 3 cases), and NB84 (3 of 5 cases) and negative for CD99. Patients with LCN and patients with c‐UH disease had similar clinical features (diagnosis at age > 1 year, often with distant metastasis). The clinical features of these patients also were significantly different from those of patients with c‐FH disease. Further analysis demonstrated that the LCN group was significantly different from both the c‐UH and c‐FH groups with respect to MYCN status (MYCN amplification, 4 of 5 vs. 3 of 17 vs. 8 of 17, respectively; P = 0.023) and survival rate (4‐year expected survival, 0% vs. 71% vs. 17%, respectively; P < 0.01). CONCLUSIONS Because of its unique clinicopathologic features, the authors propose that LCN be recognized as a distinct entity within the undifferentiated and poorly differentiated subtypes of the neuroblastoma category. Cancer 2004;100:390–7. © 2003 American Cancer Society.