Oliver Teuffel

Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia

Treatment resistance, as indicated by the presence of high levels of minimal residual disease (MRD) after induction therapy and induction consolidation, is associated with a poor prognosis in childhood acute lymphoblastic leukemia (ALL). We hypothesized that treatment resistance is an intrinsic feature of ALL cells reflected in the gene expression pattern and that resistance to chemotherapy can be predicted before treatment. To test these hypotheses, gene expression signatures of ALL samples with high MRD load were compared with those of samples without measurable MRD during treatment. We identified 54 genes that clearly distinguished resistant from sensitive ALL samples. Genes with low expression in resistant samples were predominantly associated with cell-cycle progression and apoptosis, suggesting that impaired cell proliferation and apoptosis are involved in treatment resistance. Prediction analysis using randomly selected samples as a training set and the remaining samples as a test set revealed an accuracy of 84%. We conclude that resistance to chemotherapy seems at least in part to be an intrinsic feature of ALL cells. Because treatment response could be predicted with high accuracy, gene expression profiling could become a clinically relevant tool for treatment stratification in the early course of childhood ALL.

Association between tumor necrosis factor-α promoter −308 A/g polymorphism and susceptibility to sepsis and sepsis mortality: A systematic review and meta-analysis

Objective:The tumor necrosis factor (TNF)-&agr; promoter −308 A/G polymorphism has been reported to be associated with sepsis with inconsistent results. We conducted a systematic review and meta-analysis to determine whether the TNF-&agr; −308 A/G polymorphism TNF2 (G/A or A/A) confers susceptibility to sepsis or is associated with increased risk of death from sepsis. Data Sources:We performed an electronic search of OVID MEDLINE from 1950 to June 2008 and EMBASE from 1980 to June 2008. Study Selection:From 1935 reviewed study articles, 25 were included based on predefined inclusion criteria. Data Extraction:Two reviewers independently extracted data onto standardized forms. Data Synthesis:An association between development of sepsis and the TNF2 genotype was found in the overall population (odds ratio, 2.15; 95% confidence interval, 1.45–3.19; p < .01). Stratification by ethnicity indicated that the contribution to this observation may be stronger among the Asian population (odds ratio, 3.16; 95% confidence interval, 1.92 to 5.20; p < .01) compared with other ethnicities. There was no association between the TNF2 genotype and mortality from sepsis (odds ratio, 1.48; 95% confidence interval, 0.81 to 2.70; p = .20). However, when stratified for ethnicity, there may be an increased risk for fatal outcomes among Asians (odds ratio, 10.75; 95% confidence interval, 2.98 to 38.78; p < .01). Conclusions:Our systematic review and meta-analysis demonstrates that the TNF2 polymorphism is associated with sepsis. However, TNF2 is not associated with sepsis mortality.

Cost-effectiveness of Outpatient Management for Febrile Neutropenia in Children With Cancer

OBJECTIVE: Inpatient management remains the standard of care for treatment of febrile neutropenia (FN) in children with cancer. Clinical data suggest, however, that outpatient management might be a safe and efficacious alternative for patients with low-risk FN episodes. METHODS: A cost-utility model was created to compare 4 treatment strategies for low-risk FN. The base case considered pediatric cancer patients with low-risk FN. The model used a health care payers perspective and a time horizon of 1 FN episode. Four treatment strategies were evaluated: (1) entire treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge consisting of 48 hours of inpatient observation with intravenous antibiotics followed by oral outpatient treatment (EarlyDC); (3) entirely outpatient management with intravenous antibiotics (HomeIV); and (4) entirely outpatient management with oral antibiotics (HomePO). Outcome measures were quality-adjusted FN episodes (QAFNEs), costs (Canadian dollars), and incremental cost-effectiveness ratios. Parameter uncertainty was assessed with probabilistic sensitivity analyses. RESULTS: The most cost-effective strategy was HomeIV. It was cost-saving (

Cost effectiveness of outpatient treatment for febrile neutropaenia in adult cancer patients

2732 vs

Prenatal origin of separate evolution of leukemia in identical twins.

2757) and more effective (0.66 vs 0.55 QAFNE) as compared with HomePO. EarlyDC was slightly more effective (0.68 QAFNE) but significantly more expensive (

Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and meta-analysis.

5579) than HomeIV, which resulted in an unacceptably high incremental cost-effectiveness ratio of more than

Health-related quality of life anticipated with different management strategies for paediatric febrile neutropaenia

130 000 per QAFNE. HospIV was the least cost-effective strategy because it was more expensive (

Discrete choice experiment produced estimates of acceptable risks of therapeutic options in cancer patients with febrile neutropenia

14 493) and less effective (0.65 QAFNE) than EarlyDC. CONCLUSION: The findings of this decision-analytic model indicate that the substantially higher costs of inpatient management cannot be justified on the basis of safety and efficacy considerations or patient/parent preferences.

Advances in management of low-risk febrile neutropenia.

Background:There is uncertainty whether low-risk episodes of febrile neutropaenia (FN) in adult cancer patients are best managed in the in- or outpatient setting.Methods:A Monte Carlo cost–utility model was created to compare four treatment strategies for low-risk FN: (1) treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge after 48 h in-patient observation, followed by oral outpatient treatment (EarlyDC); (3) outpatient management with IV antibiotics (HomeIV); and (4) outpatient management with oral antibiotics (HomePO). The model used a health-care payer perspective and a time horizon of one FN episode. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollars) and incremental cost-effectiveness ratios (ICER). Parameter uncertainty was assessed with probabilistic sensitivity analyses.Results:HomePO was cost saving (

Parental Perspectives on Inpatient Versus Outpatient Management of Pediatric Febrile Neutropenia

3470 vs