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Our aim was to investigate the ecological association between death from infectious disease of the respiratory system and the risk of acute lymphoid leukaemia (ALL) in children aged less than 7 years. Poisson regression analyses were carried out using overall data and gender-specific models. The study included 176 cases (92(52.3 %) boys and 84 (47.7 %) girls) of ALL in those aged 0-6 years in South Hungary. Eight cases were diagnosed before the age of 1 year. A significant risk of ALL disease was observed with higher levels of mortality from the chronic respiratory diseases (p = 0.035) and pneumonia (p = 0.010) among children aged 2-5 years (Odds Ratio for trend was 1.001 and 95%CI [1.000-1.002] and Odds ratio for trend was 1.013 and 95%CI [1.003-1.023], respectively). Significantly increased risk of childhood ALL was detected among children under 1 year of age residing in areas around birth with higher levels of mortality from influenza (Odds Ratio (OR) for trend was 1.05; 95%CI [1.01-1.09]; p = 0.012). This risk was also detected in girls (p < 0.001), but not in boys (p = 0.43). Our findings provide new evidence that will help to understand the different pattern of female and male childhood ALL occurrence , but further studies are needed using detailed individual medical history to clarify the role of influenza and other infectious diseases in the etiology of childhood ALL and to explain gender-specific effects.

The aetiology of childhood acute lymphoblastic leukaemia has been linked with spatially heterogeneous environmental exposures. The presence of spatial clustering would be consistent with geographically localized environmental exposures over long periods of time. The present study is the first to examine spatial clustering amongst children aged 0-4 years using population-based data from Hungary. The data set consisted of 134 children diagnosed with acute lymphoblastic leukaemia who were resident in part of Hungary during the period 1981-2000. Two levels of spatial aggregation were examined: counties and settlements. The Potthoff-Whittinghill and Moran I autocorrelation methods were used to test for spatial clustering. Additionally, an evaluation of the environmental changes during the study period was considered. Specifically analyses were carried out on sub-periods to investigate a possible effect of the Chernobyl catastrophe. There was statistically significant spatial clustering both at the county (estimate of extra-Poisson variation [Formula: see text], P = 0.04) and settlement levels (estimate of extra-Poisson variation [Formula: see text], P = 0.0003). At county level, the finding was attributable to clustering amongst female cases, but at settlement level, the finding was limited to male cases. There was significant spatial autocorrelation in the sub-periods immediately following the accident (1986-1990 & 1991-1995), but not before 1986, nor after 1995. A significant autocorrelation was observed during the 5 year period immediately following the accident (1986-1990, global Moran I = 0.1334, p = 0.005). The centre of significant excesses of ALL cases was located in the county of Baranya. Our study is consistent with an environmental aetiology for acute lymphoblastic leukaemia in children associated with constant exposure to an, as yet unknown, environmental factor in small geographical areas. Although a possible effect of the Chernobyl accident was found in the autocorrelation analysis, the role of chance cannot be excluded.

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.

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.