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Value of lipopolysaccharide binding protein as diagnostic marker of infection in adult cancer patients with febrile neutropenia: comparison with C-reactive protein, procalcitonin, and interleukin 6

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Abstract

Purpose

Early detection of infection is essential for initial management of cancer patients with chemotherapy-associated febrile neutropenia in the emergency department. In this study, we evaluated lipopolysaccharide binding protein (LBP) as predictor for infection in febrile neutropenia and compared with other biomarkers previously studied: C-reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6.

Methods

A total of 61 episodes of chemotherapy-associated febrile neutropenia in 58 adult cancer patients were included. Serum samples were collected on admission at emergency department and CRP, LBP, PCT, and IL-6 were measured. Patients were classified into fever of unknown origin and infection, including microbiologically and clinically documented infection, groups. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker for the diagnosis of infection.

Results

Thirty-two of the 61 episodes were classified as infection. On admission, CRP, PCT, IL-6, and LBP were significantly increased in patients with infection compared to fever of unknown origin group. Area under the ROC curve (AUC ROC) of CRP, PCT, IL-6, and LBP for discriminating both groups was 0.77, 0.88, 0.82, and 0.82, respectively, without significant difference between them. The combination of IL-6 and PCT or LBP did not lead to a significant improvement of the diagnostic accuracy of PCT or LBP alone.

Conclusions

On admission, LBP has a similar diagnostic accuracy than PCT or IL-6 for the diagnosis of infection and might be used as additional diagnostic tool in adult cancer patients with chemotherapy-associated febrile neutropenia.

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References

  1. Oude Nijhuis CS, Daenen SM, Vellenga E et al (2002) Fever and neutropenia in cancer patients: the diagnostic role of cytokines in risk assessment strategies. Crit Rev Oncol Hematol 44:163–174

    Article  CAS  PubMed  Google Scholar 

  2. Innes HE, Smith DB, O’Reilly SM et al (2003) Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study. Br J Cancer 89:43–49

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Lingaratnam S, Worth LJ, Slavin MA et al (2011) A cost analysis of febrile neutropenia management in Australia: ambulatory v.s in-hospital treatment. Aust Health Rev 35:491–500

    PubMed  Google Scholar 

  4. Klastersky J, Awada A, Paesmans M et al (2011) Febrile neutropenia: a critical review of the initial management. Crit Rev Oncol Hematol 78:185–194

    Article  PubMed  Google Scholar 

  5. de Bont ES, Vellenga E, Swaanenburg JC et al (1999) Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia. Br J Haematol 107:375–380

    Article  PubMed  Google Scholar 

  6. von Lilienfeld-Toal M, Dietrich MP, Glasmacher A et al (2004) Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein. Eur J Clin Microbiol Dis 23:539–544

    Google Scholar 

  7. Kim Y, Lee Y, Ahn S et al (2011) The usefulness of procalcitonin and C-reactive protein as early diagnostic markers of bacteremia in cancer patients with febrile neutropenia. Cancer Res Treat 43:176–180

    Article  PubMed Central  PubMed  Google Scholar 

  8. Jimeno A, García A, del Val O et al (2004) Assessment of procalcitonin as a diagnostic and prognostic Marker in Patients with Solid Tumors and Febrile Neutropenia. Cancer 100:2462–2469

    Article  CAS  PubMed  Google Scholar 

  9. Urbonas V, Eidukaité A, Tamuliené I (2012) Increased interleukin-10 levels correlate with bacteremia and sepsis in febrile neutropenia pediatric oncology patients. Cytokine 57:313–315

    Article  CAS  PubMed  Google Scholar 

  10. Reitman AJ, Pisk RM, Gates JV et al (2012) Serial procalcitonin levels to detect bacteremia in febrile neutropenia. Clin Pediatr (Phila) 51:1175–1183

    Article  Google Scholar 

  11. Mian A, Becton D, Saylors R et al (2012) Biomarkers for risk stratification of febrile neutropenia among children with malignancy: a pilot study. Pediatr Blood Cancer 59:238–245

    Article  PubMed  Google Scholar 

  12. Miedema KG, de Bont ES, Elferink RF et al (2011) The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia. Support Care Cancer 19:1593–1600

    Article  PubMed Central  PubMed  Google Scholar 

  13. Hatzistilianou M, Rekliti A, Athanassiadou F et al (2010) Procalcitonin as an early marker of bacterial infection in neutropenic febrile children with acute lymphoblastic leukemia. Inflamm Res 59:339–347

    Article  CAS  PubMed  Google Scholar 

  14. Diepold M, Noellke P, Duffner U et al (2008) Performance of interleukin-6 and interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk. BMC Infect Dis 8:28

    Article  PubMed Central  PubMed  Google Scholar 

  15. Prat C, Sánchez JM, Domínguez J et al (2008) Evaluation of procalcitonin, neopterin, C-protein reactive, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia. Leuk Lymphoma 49:1572–1581

    Article  Google Scholar 

  16. Ortega M, Rovira M, Filella X et al (2004) Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation. Br J Haematol 126:372–376

    Article  CAS  PubMed  Google Scholar 

  17. Robinson JO, Lamoth F, Bally F et al (2011) Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent fever? PLoS One 6:e18886

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Oude Nijhuis CS, Vellenga E, Daenen SM et al (2003) Lipopolysaccharide-binding protein: a possible diagnostic marker for Gram-negative bacteremia in neutropenic cancer patients. Intensive Care Med 29:2157–2161

    Article  PubMed  Google Scholar 

  19. Kitanovski L, Jazbec J, Hojker S et al (2014) Diagnostic accuracy of lipopolysaccharide-binding protein for predicting bacteremia/clinical sepsis in children with febrile neutropenia: comparison with interleukin-6, procalcitonin, and C-reactive protein. Support Care Cancer 22:269–277

    Article  PubMed  Google Scholar 

  20. Schumann R, Zweigner J (1999) A novel acute-phase marker: lipopolysaccharide binding protein (LBP). Clin Chem Lab Med 37:271–274

    Article  CAS  PubMed  Google Scholar 

  21. Zweigner J, Schumann RR, Wener JR (2006) The role of lipopoysaccharide binding protein in modulating the innate immune response. Microbes Infect 8:946–952

    Article  CAS  PubMed  Google Scholar 

  22. Faure E, Equils O, Sieling PA (2000) Bacterial lypopolysaccharide activates NF-KappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem 275:11058–11063

    Article  CAS  PubMed  Google Scholar 

  23. Klastersky J, Paesmans M, Rubenstein EB et al (2000) The multinational association for supportive care in cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenia cancer patients. J Clin Oncol 18:3038–3051

    CAS  PubMed  Google Scholar 

  24. Hughes WT, Armstrong D, Bodey GP et al (2002) 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34:730–751

    Article  PubMed  Google Scholar 

  25. Levy MM, Fink MP, Marshall JC et al (2003) International Sepsis Definitions Conference: SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference

  26. Gudiol F, Berenguer J, Lizasoaín M et al (2000) Infecciones en el paciente neutropénico. In: Aguado JM, Almirante B, Fortín J (eds) Procedimientos en Microbiología Clínica. [consulted 6/2013]. Available at www.seimc.org/documentoscientíficos/protocolos clínicos2000

  27. Cisneros JM, Cobo J, Pujol M et al (2007) Guía para el diagnóstico y tratamiento del paciente con bacteriemia. Guías de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Enferm Infecc Microbiol Clin 25:111–130

    Article  Google Scholar 

  28. Talcott JA, Finberg R, Mayer RJ et al (1988) Risk assessment in cancer patients with fever and neutropenia. Clinical identification of a low-risk subgroup at presentation. Arch Intern Med 148:2561–2568

    Article  CAS  PubMed  Google Scholar 

  29. Sakr Y, Sponholz C, Tuche F et al (2008) The role of procalcitonin in febrile neutropenic patients: review of the literature. Infection 36:396–407

    Article  CAS  PubMed  Google Scholar 

  30. Julián-Jiménez A, Candel-González FJ, González del Castillo J (2014) Utilidad de los biomarcadores de inflamación e infección en los servicios de urgencias. Enferm Infecc Microbiol Clin 32:177–190

    Article  PubMed  Google Scholar 

  31. Riedel S (2012) Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis. Diagn Microbiol Infect Dis 73:221–227

    Article  CAS  PubMed  Google Scholar 

  32. Gómez-Gerique JA, Ortiz-Espejo M, Torrealba-Rodríguez M et al (2010) Evaluación de la capacidad diagnóstica y pronóstica de procalcitonina, proteína C reactiva, interleucina-6 y proteína fijadora del lipopolisacárido en pacientes con sospecha de sepsis. Rev Lab Clin 3:12–19

    Google Scholar 

  33. Ratzinger F, Schuardt M, Eichbichler K et al (2013) Utility of sepsis biomarkers and the infection probability score to discriminate sepsis and systemic inflammatory response syndrome in standard care patients. PLoS One 8:e82946

    Article  PubMed Central  PubMed  Google Scholar 

  34. Engel A, Steinbach G, Kern P et al (1999) Diagnostic value of procalcitonin serum levels in neutropenic patients with fever: comparison with interleukin-8. Scand J Infect Dis 31:185–189

    Article  CAS  PubMed  Google Scholar 

  35. Schuetz P, Amin DN, Greenwald JL (2012) Role of procalcitonin in managing adult patients with respiratory tract infections. Chest 141:1063–1073

    Article  PubMed  Google Scholar 

  36. Kaya S, Köksal I, Mentese A et al (2013) The significance of serum urokinase plasminogen activation receptor (suPAR) in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies. Int J Infect Dis 17:e1056–e1059

    Article  CAS  PubMed  Google Scholar 

  37. Gac AC, Parienti JJ, Chantepie S et al (2011) Dynamics of procalcitonin and bacteremia in neutropenic patients with acute myeloid leukaemia. Leuk Res 35:1294–1296

    Article  CAS  PubMed  Google Scholar 

  38. Kwofie L, Rapoport BL, Fickl H et al (2012) Evaluation of circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients eith chemotherapy-associated febrile neutropenia: a pilot study. Ann Hematol 91:605–611

    Article  CAS  PubMed  Google Scholar 

  39. Tan BH, Png ME, Yeo CP, Wong GC (2014) Procalcitonin in febrile neutropenia-timing is important. Support Care Cancer 22:583–584

    Article  PubMed  Google Scholar 

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Acknowledgments

The first author had full control of primary data. The journal is allowed to review the data, if required.

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Correspondence to Luis García de Guadiana-Romualdo.

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García de Guadiana-Romualdo, L., Español-Morales, I., Cerezuela-Fuentes, P. et al. Value of lipopolysaccharide binding protein as diagnostic marker of infection in adult cancer patients with febrile neutropenia: comparison with C-reactive protein, procalcitonin, and interleukin 6. Support Care Cancer 23, 2175–2182 (2015). https://doi.org/10.1007/s00520-014-2589-1

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