Influence of cranial radiotherapy on outcome in children with acute lymphoblastic leukemia treated with contemporary therapy

Purpose We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL). Patients and Methods We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0%to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission. Using a random effects model, with CRT as a dichotomous covariate, we performed a single-arm metaanalysis to compare event-free survival and cumulative incidence of isolated or any CNS relapse and isolated bone marrow relapse in high-risk subgroups of patients who either did or did not receive CRT. Results Although there was significant heterogeneity in all outcome end points according to trial, CRT was associated with a reduced risk of relapse only in the small subgroup of patients with overt CNS disease at diagnosis, who had a significantly lower risk of isolated CNS relapse (4% with CRT v 17% without CRT; P = .02) and a trend toward lower risk of any CNS relapse (7% with CRT v 17% without CRT; P = .09). However, this group had a relatively high rate of events regardless of whether or not they received CRT (32% [95% CI, 26% to 39%] v 34% [95% CI, 19% to 54%]; P = .8). Conclusion CRT does not have an impact on the risk of relapse in children with ALL treated on contemporary protocols

RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia

RAS pathway mutations have been linked to relapse and chemotherapy resistance in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive data on the frequency and prognostic value of subclonal mutations in well-defined subgroups using highly sensitive and quantitative methods are lacking. Targeted deep sequencing of 13 RAS pathway genes was performed in 461 pediatric BCP-ALL cases at initial diagnosis and in 19 diagnos

Experimentelle Untersuchungen zur Eignung von Kanalsystemen für Linerleckortung und Dränage in einem Spannbetonbehälter

The internal surfaces of prestressed concrete pressure vessels are fitted with a steel liner to preserve the gas tightness of the primary circuit. Because of the high quality manufacture and the loading conditions a liner failure can be practically excluded. However, if it is hypothetically assumed, that a leak develops during reactor operation, it may be difficult to determine the position of the leak, because the liner area is very large. For tightness surveillance and for venting channel systems installed in close proximity to the liner are suitable. The suitability of such channels for leak detection, localisation and venting was investigated experimentally. A concrete wall (length 2,5 m, height 2,0 m, thickness 0,5 m) was constructed, covered on one side with a steel liner. Behind the liner two different channel systems have been installed. For the simulation of leaks holes were drilled into the liner. The experimental programm contained the following measurements: - determination of gas flow rates into the different leaks, - distribution of leakage gas over the array of channels, - determination of pressures into the concrete and immediatelybehind the liner. The experiments have shown, that channel arrays immediately adjacent to the liner are the most suitable systems for localisation and controlled exhaust of leakage gas. The suitability decreases , if the channels are set into the concrete somewhat distant from the liner