Background. Fever in neutropenia (FN) remains an unavoidable, potentially lethal complication of chemotherapy. Timely administration of empirical broad-spectrum intravenous antibiotics has become standard of care. But the impact of time to antibiotics (TTA), the lag period between recognition of fever or arrival at the hospital to start of antibiotics, remains unclear. Here we aimed to analyze the association between TTA and safety relevant events (SRE) in data from a prospective multicenter study. Procedure. We analyzed the association between time from recognition of fever to start of antibiotics (F-TTA) and SRE (death, admission to intensive care unit (ICU), severe sepsis and bacteremia) with three-level mixed logistic regression. We adjusted for possible triage bias using a propensity score and stratified the analysis by severity of disease at presentation. Results. We analyzed 266 FN episodes, including 53 (20%) with SRE, reported in 140 of 269 patients recruited from April 2016 to August 2018. F-TTA (median, 120min; interquartile range, 49 to 180min) was not associated with SRE, with a trend for less SREs in episodes with longer F-TTA. Analyses applying the propensity score suggested a relevant triage bias. Only in patients with severe disease at presentation there was a trend for an association of longer TTA with more SRE. Conclusion. We found little evidence that longer TTA leads to a higher risk of poor clinical outcome in pediatric patients with FN, except for those with severe disease at presentation. We saw strong evidence for triage bias which could only be partially adjusted.

Background Fever in neutropenia (FN) remains a frequent complication in pediatric patients undergoing chemotherapy for cancer. There are only conflicting and weak recommendations for and against antibiotic prophylaxis during chemotherapy. Procedure Pediatric patients were observed in a prospective multicenter study (NCT02324231). A score predicting the risk to develop FN with safety relevant events (SRE; bacteremia, severe sepsis, intensive care unit admission, death) was developed using multivariate mixed Poisson regression. Its predictive performance was assessed by internal cross-validation and compared with the performance of published rules. Results In 238 patients, 318 FN episodes were recorded, including 53 (17%) with bacteremia and 68 (21%) with SRE. The risk prediction score used three variables: chemotherapy intensity, time since diagnosis and type of malignancy. Its cross-validated performance, assessed by the time needed to cover (TNC) one event, exceeded the performance of published rules. Two clinically useful score thresholds were found: a threshold of ≥11 resulted in 2.3% time at risk and 4.1 months TNC; a threshold of ≥8 in 24.9% time at risk and 12.1 months TNC. Using external information on efficacy and timing of intermittent antibiotic prophylaxis, 4.3 months of prophylaxis were needed to prevent one FN with bacteremia, and 5.2 months to prevent one FN with SRE, using a threshold of ≥11. Conclusions This score, based on three routinely accessible characteristics, accurately identifies pediatric patients at risk to develop FN with SRE during chemothearpy. The score can help to design clinical decision rules on targeted primary antibiotic prophylaxis and corresponding efficacy studies.

Infant acute lymphoblastic leukemia (infant ALL) is known for its poor prognosis. Current treatment protocols include aggressive chemotherapy and allogeneic stem cell transplantation but prognosis remains poor. Immunotherapy is a new approach with promising results. CAR-T cell therapy has recently been approved for relapsed or refractory childhood ALL but lacks documentation regarding infant ALL. We describe here two cases of patients suffering from infant ALL who were treated with CAR-T cell therapy, the feasibility and efficiency of treatment and their outcome.