Predicting Fever in Neutropenia with Safety Relevant Events in Children
Undergoing Chemotherapy for Cancer: the Prospective Multicenter SPOG
2015 FN Definition Study
Abstract
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.