Predicting Adverse Events in Children With Fever and Chemotherapy-Induced Neutropenia: The Prospective Multicenter SPOG 2003 FN Study

Abstract

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients

“…We consider clinical signs of infection/sepsis are more relevant for patient's prognosis than assessment based predominantly on microbiologically proven positive blood culture. This opinion is also supported by recent studies and by our empirical experience as well [14,31].…”

First‐day step‐down to oral outpatient treatment versus continued standard treatment in children with cancer and low‐risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

“…Multiorgan failure led to death 10 days after presentation despite cidofovir therapy [36]. This case illustrates that, by definition, risk-prediction rules are not perfect [9,18]. Since secondary deteriorations are well-known in children with FN [24,37,38], close follow-up is essential after step-down to outpatient management.…”

“…Except for the induction phase of acute leukemia, it was recommended to suspend chemotherapy until the end of severe neutropenia. The treating physician decided on further diagnostic procedures like peripheral blood cultures, urine culture, chest radiography, and supportive measures [18].…”

“…Safety was defined as the absence of any serious medical complication (SMC) resulting from infection after randomization. SMCs included death, complications requiring pediatric intensive care unit treatment, and potentially life-threatening complications as judged by the treating physician [3,17,18,23,24].…”

“…AEs included SMCs, microbiologically defined infections (positive bacterial or fungal culture from a normally sterile body fluid or compartment, detection of a viral antigen or product of polymerase chain reaction by a validated microbiologic method) and radiologically confirmed pneumonias [18].…”