Systematic review and meta-analysis of the discriminatory performance of risk prediction rules in febrile neutropaenic episodes in children and young people

Introduction Febrile neutropaenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer, yet many children are aggressively over-treated. We aimed to undertake a systematic review and meta-analysis to summarise evidence on the discriminatory ability and predictive accuracy of clinical decision rules (CDR) of risk stratification in febrile neutropaenic episodes. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, using random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100453. Results We found 20 studies describing 16 different CDR assessed in 8388 episodes of FNP. No study compared different approaches and only one CDR had been subject to testing across multiple datasets. This review cannot conclude that any system is more effective or reliable than any other. Conclusion To maximise the value of the information already collected by these and other cohorts of children with febrile neutropaenia, an individual-patient-data (IPD) meta-analysis is required to develop and test new and existing CDR to improve stratification and optimise therapy.

[1]  Kim G. Adcock,et al.  Evaluation of Empiric Vancomycin Therapy in Children with Fever and Neutropenia , 1999, Pharmacotherapy.

[2]  Steve Goodacre,et al.  Meta-Analysis: The Value of Clinical Assessment in the Diagnosis of Deep Venous Thrombosis , 2005, Annals of Internal Medicine.

[3]  C Gatsonis,et al.  Meta‐analysis of Diagnostic Test Accuracy Assessment Studies with Varying Number of Thresholds , 2003, Biometrics.

[4]  R. Gonin,et al.  Predicting the risk of bacteremia in childen with fever and neutropenia. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Roger M. Harbord,et al.  METANDI: Stata module to perform meta-analysis of diagnostic accuracy , 2008 .

[6]  S. Richards,et al.  Progressive reduction in treatment‐related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI) , 2001, British journal of haematology.

[7]  H. Patel,et al.  Management of febrile neutropenia in pediatric oncology patients: A Canadian survey , 2007, Pediatric blood & cancer.

[8]  P. Bossuyt,et al.  Empirical evidence of design-related bias in studies of diagnostic tests. , 1999, JAMA.

[9]  L. Elting,et al.  The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. O'Ryan,et al.  Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  Y. Bertrand,et al.  Trends in treatment‐related deaths (TRDs) in childhood cancer and leukemia over time: A follow‐up of patients included in the childhood cancer registry of the Rhône‐Alpes region in France (ARCERRA) , 2008, Pediatric blood & cancer.

[12]  S. Dzik.  Early goal-directed therapy in the treatment of severe sepsis and septic shock , 2002 .

[13]  C. Mullen,et al.  Clinical parameters associated with low bacteremia risk in 1100 pediatric oncology patients with fever and neutropenia , 2001, Cancer.

[14]  J. Stockman.  A Proposed Score for Predicting Severe Infection Complications in Children With Chemotherapy-induced Febrile Neutropenia , 2008 .

[15]  G H Guyatt,et al.  Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group. , 2000, JAMA.

[16]  G. Ensinck,et al.  A prospective, multicentric scoring system to predict mortality in febrile neutropenic children with cancer , 2007, Cancer.

[17]  J. Habbema,et al.  Prognostic modelling with logistic regression analysis: a comparison of selection and estimation methods in small data sets. , 2000, Statistics in medicine.

[18]  B. Phillips,et al.  Variation in policies for the management of febrile neutropenia in United Kingdom Children’s Cancer Study Group centres , 2006, Archives of Disease in Childhood.

[19]  P. Riikonen,et al.  Fever and neutropenia in children with cancer: diagnostic parameters at presentation , 1993, Acta paediatrica.

[20]  J. García,et al.  Criterios de riesgo de bacteriemia en el paciente oncológico neutropénico febril pediátrico , 2005 .

[21]  M. Gultekin,et al.  EPISODES OF FEVER AND NEUTROPENIA IN CHILDREN WITH CANCER IN A TERTIARY CARE MEDICAL CENTER IN TURKEY , 2006, Pediatric hematology and oncology.

[22]  Andrew Thomas,et al.  WinBUGS - A Bayesian modelling framework: Concepts, structure, and extensibility , 2000, Stat. Comput..

[23]  S. Pusek,et al.  Infection risk factors in febrile, neutropenic children and adolescents. , 1996, Pediatric hematology and oncology.

[24]  Patrick M M Bossuyt,et al.  Differences between univariate and bivariate models for summarizing diagnostic accuracy may not be large. , 2009, Journal of clinical epidemiology.

[25]  Gilles Clermont,et al.  The epidemiology of severe sepsis in children in the United States. , 2003, American journal of respiratory and critical care medicine.

[26]  W. Sauerbrei,et al.  Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. , 1994, Journal of the National Cancer Institute.

[27]  M. O'Ryan,et al.  Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  E. Steliarova-Foucher,et al.  Cancer in children and adolescents in Europe: developments over 20 years and future challenges. , 2006, European journal of cancer.

[29]  G. Heller,et al.  The identification of febrile, neutropenic children with neoplastic disease at low risk for bacteremia and complications of sepsis , 1996, Cancer.

[30]  Patrick Royston,et al.  Multivariable Model-Building: A Pragmatic Approach to Regression Analysis based on Fractional Polynomials for Modelling Continuous Variables , 2008 .

[31]  A. Hirt,et al.  Identification of children presenting with fever in chemotherapy-induced neutropenia at low risk for severe bacterial infection. , 2003, Medical and pediatric oncology.

[32]  R. Klaassen,et al.  "Low-risk" prediction rule for pediatric oncology patients presenting with fever and neutropenia. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  S. Parsons,et al.  Evaluation of Risk Prediction Criteria for Episodes of Febrile Neutropenia in Children With Cancer , 2002, Journal of pediatric hematology/oncology.

[34]  M. Paesmans,et al.  A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies , 1997, British journal of haematology.

[35]  J. Marcin,et al.  Children With Cancer, Fever, and Treatment-Induced Neutropenia: Risk Factors Associated With Illness Requiring the Administration of Critical Care Therapies , 2004, Pediatric emergency care.

[36]  P. Breitfeld,et al.  Value of Electronic Data for Model Validation and Refinement: Bacteremia Risk in Children With Fever and Neutropenia , 2002, Journal of pediatric hematology/oncology.

[37]  Akers,et al.  Systematic Reviews [ressource électronique]. CRD's guidance for undertaking reviews in health care , 2009 .

[38]  P. Bossuyt,et al.  BMC Medical Research Methodology , 2002 .

[39]  P C Lambert,et al.  Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future , 2003, British Journal of Cancer.