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Background: Recurrent genetic lesions provide basis for risk assessment in pediatric acute lymphoblastic leukemia (ALL). However, current prognostic classifiers rely on a limited number of predefined sets of alterations., Methods: Disease-relevant copy number aberrations (CNAs) were screened genome-wide in 260 children with B-cell precursor ALL. Results were integrated with cytogenetic data to improve risk assessment., Results: CNAs were detected in 93.8% (n = 244) of the patients. First, cytogenetic profiles were combined with IKZF1 status (IKZF1 normal , IKZF1 del and IKZF1 plus ) and three prognostic subgroups were distinguished with significantly different 5-year event-free survival (EFS) rates, IKAROS-low (n = 215): 86.3%, IKAROS-medium (n = 27): 57.4% and IKAROS-high (n = 18): 37.5%. Second, contribution of genetic aberrations to the clinical outcome was assessed and an aberration-specific score was assigned to each prognostically relevant alteration. By aggregating the scores of aberrations emerging in individual patients, personalized cumulative values were calculated and used for defining four prognostic subgroups with distinct clinical outcomes. Two favorable subgroups included 60% of patients (n = 157) with a 5-year EFS of 96.3% (excellent risk, n = 105) and 87.2% (good risk, n = 52), respectively; while 40% of patients (n = 103) showed high (n = 74) or ultra-poor (n = 29) risk profile (5-year EFS: 67.4% and 39.0%, respectively)., Conclusions: PersonALL, our conceptually novel prognostic classifier considers all combinations of co-segregating genetic alterations, providing a highly personalized patient stratification., (© 2023. The Author(s).)

The Hungarian Pediatric Oncology Network provides centralized treatment and population-based registration for cases of childhood cancer since 1973. We collected and analized data on late mortality, secondary malignancies and cardiac diseases in survivors (> 5 years) of childhood cancer to evaluate long-term risks. We extracted all solid tumour cases (3,650 followed up for 5-39.3 years, diagnosis: 1973-2008) from the database of the Hungarian Childhood Cancer Registry and checked against the Population Registry. Among the 301 patients who died after 5 years (8.2%) the most common causes of death were progression of primary cancer (52.5%), secondary malignancies (16%) and cardiovascular diseases (8%). Late mortality rates (SMR, total: 35,006 pyrs) showed highly elevated risk of death (SMR: 10.7 95% CI 9-12.4) for the second 5 years of follow up and moderately elevated risk for 10-year survivors (SMR: 3.5 95% CI 3-4.1). Marked differences were detected in the pattern of causes of death between diagnostic groups of primary cancer; with highest risks beyond 10 years for CNS tumours, Hodgkin disease, osteosarcoma and advanced stage neuroblastoma. The longstanding mortality risk for 5-year survivors underlines the need for tailored long-term follow-up and monitoring of late consequences according to the context of different primary diseases of childhood cancer.

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 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.