• Paediatric cancer patients face an increased risk of nosocomial bloodstream infections (BSIs). • In most cases, these BSIs are associated with the use of a long-term central venous catheter (Broviac, Port), severe and prolonged immunosuppression (e.g. neutropenia) and other chemotherapy-induced alterations of host defence mechanisms (e.g. mucositis). What is New: • This study is the first multicentre study confirming relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. • It describes the epidemiology of nosocomial BSI in paediatric cancer patients mainly outside the stem cell transplantation setting during conventional intensive therapy and argues for prospective surveillance programmes to target and evaluate preventive bundle interventions.

Atypical teratoid rhabdoid tumour (ATRT) is a malignant tumour of the central nervous system with a dismal prognosis. There is no consensus on optimal treatment and different multimodal strategies are currently being used in an attempt to improve outcomes. To evaluate the impact of high-dose chemotherapy followed by autologous stem-cell rescue (HD48 SCR), radiotherapy (RT) at first line, intrathecal chemotherapy (IT) and extent of surgical resection upon recurrence-free survival (RFS) and overall survival (OS). An online database search identified prospective and retrospective studies focused on the treatment of children and adolescents with newly diagnosed ATRT. Clinical, therapeutic and outcome data were extracted and an individual pooled data analysis was conducted. Out of 389 publications, 12 manuscripts were included in our review. Data from 332 patients were analysed. Median age at diagnosis was 37 months (range 1-231). HD-SCR, RT and IT had been administered to 28.6% (58/203), 49.6% (118/238) and 21% (65/310) of the patients, respectively. Gross total resection (GTR) had been achieved in 46.5% (152/327) of the cases. In the multivariate analysis, hazard ratios (95% Confidence Interval) for HD-SCR were: RFS-HR = 0.570 (0.357-0.910) p = 0.019, and OS-HR = 0.388 (0.214-0.704) p = 0.002; and for RT: RFS-HR = 0.551 (0.351-0.866) p = 0.01, and OS-HR = 0.393 (0.216-0.712) p = 0.002. IT and GTR were not significantly associated with improved RFS or OS in the multivariate analysis. In our pooled data review, HD-SCR and RT at first line were associated with improved outcomes in children and adolescents with newly diagnosed ATRT.

The reduced dose of 5,000 U/m2 E. coli ASNase for induction treatment succeeded to achieve an activity level above 100 U/L in more than 90% of all samples. They confirm that dose reduction is reasonable and provide the basis for future treatment strategies employing ASNase.

Children with high-risk neuroblastoma who fail to achieve adequate metastatic response after induction chemotherapy have dismal outcome and new therapeutic strategies are needed. However, timing of introduction of novel agents still remains under discussion. Given an increase in number of phase I-II studies of molecularly targeted drugs in neuroblastoma, it is crucial to determine, as early as possible, which patients may be suitable candidates for new therapeutic strategies. This single-center retrospective analysis of patients with high-risk neuroblastoma showed that the addition of conventional chemotherapy improved the quality of metastatic response only for the group of patients with partial response. It is therefore proposed to develop stratification criteria for those patients very unlikely to benefit from a plethora of additional lines of treatment, but might benefit from introduction of novel agents.

BackgroundTherapeutic drug monitoring (TDM) of asparaginase (ASNase), a fundamental element of acute lymphoblastic leukemia treatment, was integrated in the ALL‐BFM 2000 protocol on a voluntary basis.MethodsOver a 5‐year period, 127 patients (1,355 samples) were monitored for asparaginase activity in a single‐center setting. We report monitoring data from throughout the ASNase containing treatment elements. Additional information obtained on risk stratification, minimal residual disease (MRD), steroid randomization and relapse is discussed in relation to ASNase activity.ResultsAt completion of the induction phase 93% (115/124) of patients showed sufficient ASNase activity (5,000 U/m2 Escherichia coli ASNase), 77 of 86 (90%) monitored patients finished the first re‐intensification element without requiring Erwinia ASNase. MRD, risk stratification and steroid randomization were not associated with significant differences in ASNase activity. Of patients who relapsed, only 25% (3/12) were able to maintain sufficient ASNase activity after E. coli ASNase.ConclusionThis single‐center data set gives a true and unbiased insight into clinical reality of ASNase therapy. It shows no significant relationship between MRD positivity or risk stratification and ASNase treatment intensity. Overall, within the ALL‐BFM 2000 trial, 90% of patients completed first re‐intensification without requiring third‐line Erwinia ASNase. Pediatr Blood Cancer 2011; 57: 378–384. © 2011 Wiley‐Liss, Inc.

Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised children. Disease control depends on prevention, early diagnosis, predictive microbiological information, prompt and appropriate treatment and restoration of host defenses. Relative to adults, invasive aspergillosis in children and adolescents is unique in its clinical presentation, epidemiology, and in particular, the utility of newer diagnostic tools and the pharmacokinetics of active antifungal agents. Here we review the presentation and epidemiology of invasive aspergillosis in children and adolescents and discuss the value of current diagnostic tools and strategies and options for treatment and prevention in this special population.

In the publications analyzed, we found only limited information concerning methods and reflections on ethical principles of the trials. Improvements are thus necessary and possible. We suggest how such trials and their respective publications can be optimized for these aspects.

Background The European Neuroblastoma Study Group 5 (ENSG5) trial showed that time‐intensive “rapid” induction chemotherapy (COJEC) was superior to “standard” 3‐weekly chemotherapy for children with high‐risk metastatic neuroblastoma. Long‐term outcomes of the ENSG5 trial were analysed. Procedure Patients with metastatic neuroblastoma aged ≥12 months were randomly assigned to “standard” or “rapid” induction, receiving the same chemotherapy drugs and doses. Event‐free survival (EFS) and overall survival (OS) were analysed and prognostic factors evaluated. Amongst patients surviving >5 years, a population of children with persistent metastatic disease after the end of treatment was identified and described. Results Ten‐year EFS was 18.2% (95% confidence interval: 12.2–25.2) for the “standard” arm and 26.8% (19.5–34.7) for the “rapid” arm (hazard ratio [HR] 0.85, P = 0.28). Ten‐year OS for the “standard” arm was 19.7% (13.4–26.8) and 28.3% (20.8‐36.2) for the “rapid arm” (HR 0.83, P = 0.19). There was a trend for worse EFS and OS for patients having MYCN amplification (HR 1.37 and 1.40, respectively) and those with partial and mixed response to induction (HR 1.69 and 1.75 for EFS and 1.66 and 2.00 for OS, respectively). Among 69 patients who survived >5 years, six had persistent metastatic disease after the end of treatment. Conclusion The benefit of the “rapid” induction regimen seems to be maintained in the long term, although the small number of survivors could justify the lack of statistical significance. MYCN amplification and poor metastatic response to induction could be associated with worse outcomes. A small group of patients with persistent metastatic disease that survived long term has been described.