Biomarkers and Fever During Neutropenia in Pediatric Cancer
Biomarkers and Fever During Neutropenia in Pediatric Cancer
Background: Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. The role of biomarkers in predicting morbidity and mortality associated with FN in children has been explored with varying results. This systematic review identified, critically appraised and synthesized information on the use of biomarkers for the prediction of outcome of FN in children/young adults, updating a review of initial assessment and adding further analysis of their value at reassessment.
Methods: This review was conducted in accordance with the Centre for Reviews and Dissemination Methods, using 3 different random effects meta-analysis models.
Results: Thirty-seven studies involving over 4689 episodes of FN in children were assessed, including an additional 13 studies investigating 18 biomarkers in 1670 FN episodes since the original review. Meta-analysis was possible for admission C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 and interleukin-8 in their ability to detect significant infection. Marked heterogeneity exists, precluding clear clinical interpretation of the results. Qualitative synthesis of the role of serial biomarkers suggests their predictive ability may be more pronounced at 24 to 48 hours compared with admission. Direct comparisons of the discriminatory power of admission values of PCT and CRP showed PCT generally had a better discriminatory estimate of serious infection than CRP.
Conclusions: There remains a paucity of robust and reproducible data on the use of biomarkers in prediction of serious infection in children with FN. Available evidence suggests PCT has better discriminatory ability than CRP and that the role of serial biomarkers warrants further study.
Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. Fortunately, improvements in supportive care have dramatically reduced infection-related mortality. The focus has now been turned toward reducing the associated morbidity and healthcare costs, as well as optimizing the quality of life of the child and their family during these episodes. In particular, there has been increasing attention directed toward the development of a clinical decision rule that identifies children with FN at low risk of serious infection and medical complications who may be suitable for reduced intensity treatment.
The Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer Secretariat previously conducted a systematic review in 2009 of the value of serum biomarkers in the initial risk assessment of FN episodes. The review concluded that there was marked heterogeneity in the reports, but that data were suggestive of the more powerful predictive ability of procalcitonin (PCT), interleukin (IL)-6 and IL-8 over C-reactive protein (CRP). Since this review was undertaken, there have been further publications. Additionally, the question of the value of these markers in the reassessment of individuals, to determine their response to therapy and enhance their subsequent treatment, has not been systematically addressed.
A biomarker has been broadly defined as a "characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." This systematic review aims to identify, critically appraise and synthesize information on the use of serum biomarkers for the prediction of adverse outcomes of FN episodes in children/young adults, both by updating the previous review of their initial value, and conducting a further analysis based around their potential value at reassessment.
Abstract and Introduction
Abstract
Background: Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. The role of biomarkers in predicting morbidity and mortality associated with FN in children has been explored with varying results. This systematic review identified, critically appraised and synthesized information on the use of biomarkers for the prediction of outcome of FN in children/young adults, updating a review of initial assessment and adding further analysis of their value at reassessment.
Methods: This review was conducted in accordance with the Centre for Reviews and Dissemination Methods, using 3 different random effects meta-analysis models.
Results: Thirty-seven studies involving over 4689 episodes of FN in children were assessed, including an additional 13 studies investigating 18 biomarkers in 1670 FN episodes since the original review. Meta-analysis was possible for admission C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 and interleukin-8 in their ability to detect significant infection. Marked heterogeneity exists, precluding clear clinical interpretation of the results. Qualitative synthesis of the role of serial biomarkers suggests their predictive ability may be more pronounced at 24 to 48 hours compared with admission. Direct comparisons of the discriminatory power of admission values of PCT and CRP showed PCT generally had a better discriminatory estimate of serious infection than CRP.
Conclusions: There remains a paucity of robust and reproducible data on the use of biomarkers in prediction of serious infection in children with FN. Available evidence suggests PCT has better discriminatory ability than CRP and that the role of serial biomarkers warrants further study.
Introduction
Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. Fortunately, improvements in supportive care have dramatically reduced infection-related mortality. The focus has now been turned toward reducing the associated morbidity and healthcare costs, as well as optimizing the quality of life of the child and their family during these episodes. In particular, there has been increasing attention directed toward the development of a clinical decision rule that identifies children with FN at low risk of serious infection and medical complications who may be suitable for reduced intensity treatment.
The Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer Secretariat previously conducted a systematic review in 2009 of the value of serum biomarkers in the initial risk assessment of FN episodes. The review concluded that there was marked heterogeneity in the reports, but that data were suggestive of the more powerful predictive ability of procalcitonin (PCT), interleukin (IL)-6 and IL-8 over C-reactive protein (CRP). Since this review was undertaken, there have been further publications. Additionally, the question of the value of these markers in the reassessment of individuals, to determine their response to therapy and enhance their subsequent treatment, has not been systematically addressed.
A biomarker has been broadly defined as a "characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." This systematic review aims to identify, critically appraise and synthesize information on the use of serum biomarkers for the prediction of adverse outcomes of FN episodes in children/young adults, both by updating the previous review of their initial value, and conducting a further analysis based around their potential value at reassessment.
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