Risk Prediction in Pediatric Cancer Patients With Fever and Neutropenia

Department of Infectious Diseases, Mail Stop 600, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 12/2009; 29(1):53-59. DOI: 10.1097/INF.0b013e3181c3f6f0
Source: PubMed


Background: To identify predictors for 2 risk measures—“proven invasive bacterial infection or culture-negative sepsis (IBD)” and “clinical complications (CC)”—in pediatric cancer patients with fever and neutropenia (FN).
Methods: Records of 390 patients with FN hospitalized over 2 years were reviewed. For the 332 who met inclusion criteria, one FN episode was randomly selected. Independent predictors at presentation were analyzed using multiple regression models. Optimal cut-off risk prediction scores were determined. These models were validated by bootstrap analysis.
Results: Patients' median age was 6.0 years; 66% had an underlying diagnosis of leukemia. Independent predictors of IBD (n = 56) were absolute neutrophil count <100, temperature at presentation ≥39.0°C, “sick” clinical appearance, and underlying diagnosis of acute myeloid leukemia. A total weighted score <24 reliably identified patients at low risk for IBD. Independent predictors of CC (n = 47) were relapse of malignancy, non-white race, “sick” clinical appearance, and underlying diagnosis of acute myeloid leukemia. A total weighted score <19 predicted patients at low risk for CC. Of those misclassified as low risk, 11 of 12 with IBD and 3 of 9 with CC had the outcome within 24 hours of presentation. Of the remaining patients classified as low-risk for IBD and CC, 99.5% and 97.1%, respectively, remained outcome-free after 24 hours of observation.
Conclusions: This study identifies predictors of infection/complications in pediatric patients with FN, establishes clinical cut-off scores and highlights the importance of the initial clinical impression and 24 hours of observation. These prediction models warrant prospective validation.

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    • "Five studies attempted to derive at least one CDR. Four studies examined rules to predict significant medical complications; a group of outcomes generally encompassing death, intensive care admission, significant bacterial or fungal infection, and need for organ support such as supplemental oxygen, inotropes or dialysis [7], [14], [16], [17]. Two examined rules to predict bacteraemia [16], [18], and one intensive care admission [15]. "
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    ABSTRACT: Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia.
    PLoS ONE 05/2012; 7(5):e38300. DOI:10.1371/journal.pone.0038300 · 3.23 Impact Factor
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    ABSTRACT: Abstract. Neutrophils or neutrophilic granulocytes have an important role in human im - mune response and serve to fight foreign organisms and initial infection. Neutrophil count ranges around 2,5 – 7,5x10 9 /L (varies between laboratories). They represent about 60-70 % of all white blood cells present in peripheral blood. State with decreased absolute neu - trophil count is called neutropenia. It is very important not to overlook neutropenia as it can lead to infection, especially bacterial. Neutropenia can be caused by a variety of factors, one of these being chemotherapy-induced febrile neutropenia. This type of neutropenia is caused by a direct toxic effect of cytotoxic agents on granulocytopoietic cells which in turn block neutrophil development. Febrile neutropenia represents an iatrogenic syndrome, gen - erally characterized by fever (>38,5°C) along with decreased absolute neutrophil count (<0,5x10 9 /L). It occurs frequently in patients receiving cytotoxic therapy. Febrile neutropenia is a hematological emergency which requires rapid detection and vigorous treatment with broad-spectrum antibiotics in order to stop infections, their complications and possible le - thal outcome. Key words: clinical features, febrile neutropenia, treatment
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    ABSTRACT: Inherited and acquired immune system dysfunctions associated with fever are reviewed. Recent evidence of best practices in the diagnosis and treatment of fever caused by infections in children are also discussed. Descriptive studies on clinical presentation of periodic fever and outcomes associated with and without interventions are discussed. Diagnostic evaluation and therapy of fever and neutropenia in cancer patients and challenges associated with the diagnosis of Kawasaki disease are also included. New evidence on the treatment of urinary tract infection in the neonate, and clinical evaluation tools for febrile infants, are reviewed. Immune-dysfunction as a cause of fever is not well understood. In order to target therapy appropriately, more studies are needed to understand the pathogenesis of fever in this population. Better diagnostic methods are available for detection of viruses, especially in patients with fever and neutropenia, but further investigation is required for the interpretation of those results.
    Current opinion in pediatrics 02/2011; 23(1):115-20. DOI:10.1097/MOP.0b013e328342338c · 2.53 Impact Factor
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