Journal of Kerman University of Medical Sciences

Current Issue

By Issue

By Author

Author Index

Keyword Index

About Journal

Aims and Scope

JKMU Ethical Policies

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

Metric

Editorial Policies

Data Sharing Policy

Significance of Interleukin-6 and C-Reactive Protein in Predicting Outcomes in Febrile Neutropenia in Children with Malignancy

Document Type : Original Article

Authors

Department of Pediatrics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Background: Febrile neutropenia (FN) is a common complication in children with cancer. We investigated the ability of interleukin-6 (IL-6) and C-reactive protein (CRP) to predict FN and fever in these patients.
Methods: In this cross-sectional analytical study, all eligible patients diagnosed with hematological and non-hematological cancers referred to hematology, oncology wards of Motahari Hospital in Urmia, from 2021 to 2022 were selected by convenience method. Demographic information, type of malignancy, stage of malignancy treatment, drugs receiving chemotherapy, accompanying symptoms, test results and paraclinical findings were collected. We predefined cutoff values at 30 pg/mL for IL-6 and 30 mg/dL for CRP.
Results: Of 30 pediatric cancer patients, 21 were male (70%) and nine were female (30%), with a mean age of 7.2 ± 3.46 years. The mean duration of fever and hospital stay was 3.14 ± 1.95 days and 7.85 ± 2.8 days, respectively, in the group with IL-6 levels exceeding 30 pg/mL. In contrast, for those with IL-6 levels below 30 pg/mL, the mean duration of fever and hospitalization stood at 6.0 ± 2.8 days and 10.6 ± 3.8 days, respectively. A significant association was noted between IL-6 levels and both hospital stay (P = 0.034) and fever duration (P = 0.008). Conversely, no notable correlation was evident between CRP levels and the duration of hospitalization or fever in the participants under investigation (P ≤ 0.79).
Conclusion: Our findings suggest initial serum IL-6 levels may predict FN and fever in children with cancer. This makes IL-6 a potentially valuable tool for identifying low-risk patients.

Keywords

Main Subjects

References
  1. Al Omar S, Nazer L, Alkayed K. A prospective study of febrile neutropenia in pediatric cancer patients in Jordan. J Pediatr Hematol Oncol. 2013;35(8):614-7. doi: 10.1097/ MPH.0b013e31829f3480.
  2. Zimmer AJ, Freifeld AG. Optimal management of neutropenic fever in patients with cancer. J Oncol Pract. 2019;15(1):19-24. doi: 10.1200/jop.18.00269.
  3. Arif T, Phillips RS. Updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer. Pediatr Blood Cancer. 2019;66(10):e27887. doi: 10.1002/pbc.27887.
  4. Chaudhary N, Kosaraju K, Bhat K, Bairy I, Borker A. Significance of interleukin-6 (IL-6) and C-reactive protein (CRP) in children and young adults with febrile neutropenia during chemotherapy for cancer: a prospective study. J Pediatr Hematol Oncol. 2012;34(8):617-23. doi: 10.1097/ MPH.0b013e3182677fc6.
  5. Monuszko KA, Albright B, Katherine Montes De Oca M, Thao Thi Nguyen N, Havrilesky LJ, Davidson BA. Evaluation of the clinical Index of Stable febrile neutropenia risk stratification system for management of febrile neutropenia in gynecologic oncology patients. Gynecol Oncol Rep. 2021;37:100853. doi: 10.1016/j.gore.2021.100853.
  6. Raheja R, Reddy N, Patel T, Kilambi S, Mathew AA, Majeed A. Classification of chemotherapy-induced febrile neutropenic episodes into one of the three febrile neutropenic syndromes. Cureus. 2023;15(8):e42843. doi: 10.7759/cureus.42843.
  7. von Allmen AN, Zermatten MG, Leibundgut K, Agyeman P, Ammann RA. Pediatric patients at risk for fever in chemotherapy-induced neutropenia in Bern, Switzerland, 1993-2012. Sci Data. 2018;5:180038. doi: 10.1038/ sdata.2018.38.
  8. Massaro F, Andreozzi F, Vandevoorde C, Bron D. Supportive care in older lymphoma patients to reduce toxicity and preserve quality of life. Cancers (Basel). 2023;15(22):5381. doi: 10.3390/cancers15225381.
  9. Bognini JD, Samadoulougou S, Ouedraogo M, Smart F, Kankoye DT, Sankoh O, et al. What are the trends in seeking health care for fever in children under-five in Sierra Leone? evidence from four population-based studies before and after the free health care initiative. PLoS One. 2022;17(2):e0263364. doi: 10.1371/journal.pone.0263364.
  10. Haeusler GM, Thursky KA, Slavin MA, Babl FE, De Abreu Lourenco R, Allaway Z, et al. Risk stratification in children with cancer and febrile neutropenia: a national, prospective, multicentre validation of nine clinical decision rules. EClinicalMedicine. 2020;18:100220. doi: 10.1016/j. eclinm.2019.11.013.
  11. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463-6. doi: 10.1097/COH.0b013e32833ed177.
  12. Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33(3):127-48. doi: 10.1093/intimm/dxaa078.
  13. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295. doi: 10.1101/cshperspect.a016295.
  14. Binnie A, Lage J, Dos Santos CC. How can biomarkers be used to differentiate between infection and non-infectious causes of inflammation? In: Deutschman CS, Neligan PJ, eds. Evidence- Based Practice of Critical Care. 3rd ed. Elsevier; 2020. p. 319- 24.e1. doi: 10.1016/b978-0-323-64068-8.00055-9.
  15. Kar YD, Özdemir ZC, Bör Ö. Evaluation of febrile neutropenic attacks of pediatric hematology-oncology patients. Turk Pediatri Ars. 2017;52(4):213-20. doi: 10.5152/ TurkPediatriArs.2017.5312.
  16. van der Galiën HT, Loeffen EA, Miedema KG, Tissing WJ. Predictive value of PCT and IL-6 for bacterial infection in children with cancer and febrile neutropenia. Support Care Cancer. 2018;26(11):3819-26. doi: 10.1007/s00520-018- 4249-3.
  17. Koenig C, Lehrnbecher T. Diagnostics and therapy of paediatric patients with febrile neutropenia. EJC Paediatr Oncol. 2023;2:100116. doi: 10.1016/j.ejcped.2023.100116.
  18. Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017;96(11):1775-92. doi: 10.1007/s00277-017-3098-3.
  19. Bachlitzanaki M, Aletras G, Bachlitzanaki E, Messaritakis I, Koukias S, Koulouridi A, et al. Evaluation of febrile neutropenia in hospitalized patients with neoplasia undergoing chemotherapy. Microorganisms. 2023;11(10):2547. doi: 10.3390/microorganisms11102547.
  20. Hughes WT, Armstrong D, Bodey GP, Brown AE, Edwards JE, Feld R, et al. 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis. 1997;25(3):551- 73. doi: 10.1086/513764.
  21. Chai KL, Wong J, Weinkove R, Keegan A, Crispin P, Stanworth S, et al. Interventions to reduce infections in patients with hematological malignancies: a systematic review and meta-analysis. Blood Adv. 2023;7(1):20-31. doi: 10.1182/ bloodadvances.2022008073.
  22. Kharya G, Yadav SP, Srivastava LM, Sachdeva A. Use of interleukin 6, high sensitivity CRP, TNFα and procalcitonin as early markers of sepsis in febrile neutropenic children. Blood. 2007;110(11):3852. doi: 10.1182/blood.V110.11.3852.3852.
  23. Diepold M, Noellke P, Duffner U, Kontny U, Berner R. 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. 2008;8:28. doi: 10.1186/1471-2334-8-28.
  24. Urbonas V, Eidukaitė A, Tamulienė I. The diagnostic value of interleukin-6 and interleukin-8 for early prediction of bacteremia and sepsis in children with febrile neutropenia and cancer. J Pediatr Hematol Oncol. 2012;34(2):122-7. doi: 10.1097/MPH.0b013e3182446a60.
  25. Vidal L, Ben Dor I, Paul M, Eliakim-Raz N, Pokroy E, Soares- Weiser K, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev. 2013;2013(10):CD003992. doi: 10.1002/14651858. CD003992.pub3.
  26. Shokripour M, Omidifar N, Salami K, Moghadami M, Samizadeh B. Diagnostic accuracy of immunologic biomarkers for accurate diagnosis of bloodstream infection in patients with malignancy: procalcitonin in comparison with C-reactive protein. Can J Infect Dis Med Microbiol. 2020;2020:8362109. doi: 10.1155/2020/8362109.
  27. Engel A, Mack E, Kern P, Kern WV. An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients. Infection. 1998;26(4):213-21. doi: 10.1007/bf02962366.
  28. Nikkhoo B, Mohammadi M, Hasani S, Sigari N, Borhani A, Ramezani C, et al. Elevated interleukin (IL)-6 as a predictor of disease severity among COVID-19 patients: a prospective cohort study. BMC Infect Dis. 2023;23(1):311. doi: 10.1186/ s12879-023-08294-w.
  29. Santa Cruz A, Mendes-Frias A, Oliveira AI, Dias L, Matos AR, Carvalho A, et al. Interleukin-6 is a biomarker for the development of fatal severe acute respiratory syndrome coronavirus 2 pneumonia. Front Immunol. 2021;12:613422. doi: 10.3389/fimmu.2021.613422.
  30. Hashemi Shahri SM, Dehghan J, Bameri Z, Kor A, Sharifi Mood B, Mardani M. Evaluation of serum level of interleukin-6 in patients with Crimean-Congo hemorrhagic fever in Zahedan, Iran, from 2012 to 2015. Arch Clin Infect Dis. 2016;11(3):e28029. doi: 10.5812/archcid.28029.
  31. Stryjewski GR, Nylen ES, Bell MJ, Snider RH, Becker KL, Wu A, et al. Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children. Pediatr Crit Care Med. 2005;6(2):129-35. doi: 10.1097/01. Pcc.0000149317.15274.48.
  32. Prat C, Sancho JM, Dominguez J, Xicoy B, Gimenez M, Ferra C, et al. Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia. Leuk Lymphoma. 2008;49(9):1752-61. doi: 10.1080/10428190802258956.
  33. Jaing TH, Chang CC, Chang TY, Chen SH, Wen YC, Tsay PK. Diagnostic value of C-reactive protein and interleukin-8 in risk stratification of febrile neutropenic children with allogeneic hematopoietic stem cell transplantation. Sci Rep. 2020;10(1):2894. doi: 10.1038/s41598-020-59814-6.
  34. Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: from clinical significance to quantification. Adv Sci (Weinh). 2021;8(15):e2004433. doi: 10.1002/ advs.202004433.
  35. Lindström J, Nordeman L, Hagström B. What a difference a CRP makes. A prospective observational study on how point-of-care C-reactive protein testing influences antibiotic prescription for respiratory tract infections in Swedish primary health care. Scand J Prim Health Care. 2015;33(4):275-82. doi: 10.3109/02813432.2015.1114348.
  36. Ito A, Ishida T. Diagnostic markers for community-acquired pneumonia. Ann Transl Med. 2020;8(9):609. doi: 10.21037/ atm.2020.02.182.
  37. Pepys MB. The acute phase response and C-reactive protein. In: Warrell DA, Cox TM, Firth JD, eds. Oxford Textbook of Medicine. 5th ed. Oxford: Oxford University Press; 2010. Available from: https://doi.org/10.1093/ med/9780199204854.003.121201_update_001. Accessed March 14, 2024.
  38. Boenisch S, Fae P, Drexel H, Walli AK, Fraunberger P. Are circulating levels of CRP compared to IL-6 and PCT still relevant in intensive care unit patients? Laboratoriumsmedizin. 2013;37(1):1-10. doi: 10.1515/labmed-2013-0029.
  39. Gupta M, Kini PG, Bhat YR, Aroor S. Interleukin-6 versus C-reactive protein as markers for early detection of bacteremia in febrile neutropenia in pediatric population. Indian J Med Paediatr Oncol. 2020;41(5):702-6. doi: 10.4103/ijmpo. ijmpo_257_19.
Journal of Kerman University of Medical Sciences
Volume 32
Pages 1-8
Files
Share
How to cite
Statistics