Aim: Management of febrile neutropenia is challenged by lacking microbiological and clinical documentation of infection. Procalcitonin is emerging as a new promising biomarker of infection. We aimed to undertake a systematic review evaluating the diagnostic accuracy of procalcitonin as a marker of infection in febrile neutropenia. Methods: We performed a systematic re- view of the literature using the databases MEDLINE, EMBASE and Cochrane Library including a search of the grey literature (e.g. unpublished data, web sides of relevant societies). The methodological quality was assessed using predefined criteria. The relevant data were extracted and analyzed by two authors. Results: The literature search yielded a total of 193 studies of which nine were eligible for inclusion. There was a great variation in the quality of the methodological design. A notable heterogeneity exists regarding the studied populations and the definition of the reference standards. Among the nine included studies the sensitivity ranged from 42% to 72% and the specificity ranged from 64% - 89% at a cut off value ranging from 0.5 - 0.8 ng/ml. The studied endpoint was either microbiologically or clinically documented infection. Four studies found procalcitonin superior to Creactive protein in discriminating infection from the various other causes of fever. Conclusion: Procalcitonin appears to be a promising biomarker and might add new diagnostic information in the management of febrile neutropenia.
References
[1]
Maruna, P., Nedelnikova, K. and Gürlich, R. (2000) Phy- siology and genetics of procalcitonin. Physiol Research, 49, S57-S61.
[2]
Meisner, M. (2002) Pathobiochemistry and clinical use of procalcitonin. Clinical Chemica Acta, 323, 17-29.
doi:10.1016/S0009-8981(02)00101-8
[3]
Dandona, P., Nix, D., Wilson, M.F., et al. (1994) Procal- citonin increase after endotoxin injection in normal sub- jects. The Journal of Clinical Endocrinology & Metabo- lism, 79, 1605-1608.
doi:10.1210/jc.79.6.1605
[4]
Gabay, C. and Kushner, I. (1999) Acute-phase proteins and other systemic responses to inflammation. The New England Journal of Medicine, 340, 448-454.
doi:10.1056/NEJM199902113400607
[5]
Assicot, M., Gendrel, D., et al. (1993) High serum pro- calcitonin cencentration in patients with sepsis and infec- tion. Lancet, 341, 515-518.
[6]
Schneider, H.-G. and Lam, Q.T. (2007) Procalcitonin for the clinical laboratory, a review. Pathology, 39, 383-390.
doi:10.1080/00313020701444564
[7]
Simon, L., Gauvin, F., et al. (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial in- fection, a systematic review and meta-analysis. Clinical Infectious Diseases, 39, 206-217. doi:10.1086/421997
[8]
Tang, B. and Eslick, G. (2007) Accuracy of procalcitonin for sepsis diagnosed in the critically ill patients, syste- matic review and meta-analysis. The Lancet Infectious Diseases, 7, 210-217.
doi:10.1016/S1473-3099(07)70052-X
[9]
Al-Nawas, B. and Shah, P.M. (1996) Procalcitonin in patients with and without immunosuppression and sepsis. Infection, 24, 30-32. doi:10.1007/BF01713044
[10]
Marti, F. and Cullen, M.H. (2009) Management of febrile neutropenia, ESMO clinical recommendations. Annals of Oncology, 20, 166-169. doi:10.1093/annonc/mdp163
[11]
Schwenkglenks, M., Jackish, C., Constenla, M., et al. (2006) Neutropenic event risk and impaired chemothe- rapy delivery in 6 european audits of breast cancer treat- ment. Support Care Cancer, 14, 901-909.
doi:10.1007/s00520-006-0034-9
[12]
Chang, J. (2000) Chemotherapy dose reduction and delay in clinical practice. Evaluating the risk to patient outcome in adjuvant chemotherapy for breast cancer. European Journal of Cancer, 36, S11-S14.
doi:10.1016/S0959-8049(99)00259-2
[13]
Elting, L.S., Rubenstein, E.B., et al. (1997) Outcomes of bacteremia in patients with cancer and neutropenia, ob- servations from two decades of epidemiological and cli- nical trials. Clinical Infectious Diseases, 25, 247-59.
doi:10.1086/514550
[14]
Schüttrumpf, S., Binder, L., et al. (2003) Procalcitonin, a useful discriminator between febrile conditions of diffe- rent origin in hemato-oncological patients. Annals of He- matology, 82, 98-103.
[15]
Rintala, E. (1994) Incidence and clinical significance of positive blood cultures in febrile episodes of patients with hematological malignancies. Scandinavian Journal of In- fectious Diseases, 26, 77-84.
doi:10.3109/00365549409008594
[16]
Kim, D.Y., Lee, Y.-S., et al. (2011) The usefulness of procalcitonin and C-reactive protein as early diagnostic markers of bacteremia in cancer patients with febrile neu- tropenia. Cancer Treatment and Research, 43, 176-180.
doi:10.4143/crt.2011.43.3.176
[17]
Sakr, Y,, Sponholz, C., et al. (2008) The role of procalci- tonin in febrile neutropenic patients, review of the litera- ture. Infection, 36, 396-407.
doi:10.1007/s15010-008-7374-y
[18]
Whiting, P.F., Rutjes, A.W.S., Westwood, M.E., et al. (2011) QUADAS-2, a revised tool for the diagnostic ac- curacy studies. Annals of Internal Medicine, 155, 529- 536.
[19]
Ruokonen, E., Nousiainen, T., Pulkki, K., et al. (1999) Procalcitonin concentration in patients with neutropenic fever. European Journal of Clinical Microbiology & In- fectious Diseases, 18, 283-285.
doi:10.1007/s100960050277
[20]
Engel, A., Steinbach, G., Kern, P., et al. (1999) Diagnostic value of procalcitonin serum levels in neutropenic pa- tients with fever, comparison with interleukin-8. Scandi- navian Journal of Infectious Diseases, 31, 185-189.
doi:10.1080/003655499750006254
[21]
Giamarellos-Bourboulis, E.J., Grecka, P., Poulakou, G., et al. (2001) Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clinical Infectious Diseases, 32, 1718-1725.
doi:10.1086/320744
[22]
Jimeno, A., Garcia-Velasco, A., del Val, O., et al. (2004) Assessment of procalcitonin as a diagnostic and prognos- tic marker in patients with solid tumors and febrile neu- tropenia. Cancer, 100, 2462-2469.
doi:10.1002/cncr.20275
[23]
Giamarellou, H., Giamarellos-Bourboulis, E.J., Repoussis, P., et al. (2004) Potential use of procalcitonin as a diag- nostic criterion in febrile neutropenia, experience from a multicentre study. Clinical Microbiology and Infection, 10, 628-633. doi:10.1111/j.1469-0691.2004.00883.x
[24]
Lilienfeld-Toal, M.V., Dietrich, M.P., 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. Euro- pean Journal of Clinical Microbiology & Infectious Dis- eases, 23, 539-544. doi:10.1007/s10096-004-1156-y
[25]
Ahn, S., Lee, Y.-S., Chun, Y.H., et al. (2011) Predictive factors of bacteraemia in low-risk patients with febrile neutropenia. Emergency Medicine Journal, 29, 715-719.
[26]
Gac, A.-C., Parienti, J.-J., Chantepie, S., et al. (2011) Dy- namics of procalcitonin and bacteremia in neutropenic adults with acute myeloid leukemia. Leukemia Research, 35, 1294-1296. doi:10.1016/j.leukres.2011.05.035
[27]
Kim, D.Y., Lee, Y.-S., Ahn, S., et al. (2011) The useful- ness of procalcitonin and C-reactive protein as early di- agnostic markers of bacteremia in cancer patientswith febrile neutropenia. Cancer Research and Treatment, 43, 176-180. doi:10.4143/crt.2011.43.3.176
[28]
Rapoport, B.L. (2011) Management of the cancer patient with infection and neutropenia. Seminars in Oncology, 38, 424-430. doi:10.1053/j.seminoncol.2011.03.013
[29]
Lyman, G., Michels, S., Reynolds, M., et al. (2010) Risk of mortality in patients with cancer who experience feb- rile neutropenia. Cancer, 1, 5555-5563.
[30]
Schneider, H.-G. and Lam, Q.T. (2007) Procalcitonin for the clinical laboratory, a review. Pathology, 39, 383-390.
doi:10.1080/00313020701444564
[31]
Al-Ahwal, M., Al-Sayws, F. and Johar, I. (2005) Febrile neutronpenia comparison between solid tumors and he- matological malignincies. Arab Medical Journal, 4, 4-7.
[32]
Guyatt, G., Oxman, A., Vist, G., et al. (2008) What is quality of evidence” and why is it important to clinicians? British Medical Journal, 336, 995-998.
doi:10.1136/bmj.39490.551019.BE
[33]
Whiting, P., Weswood, M., Rutjes, A., et al. (2006) Eva- luation of QUADAS, a tool for the quality assessment of diagnostic accuracy studies. BMC Medical Research Methodology, 2006, 6, 9. doi:10.1186/1471-2288-6-9
[34]
Knudsen, T.B. and Kristiansen, T.B. (2005) Issues per- taining to data extraction and classification and publica- tion bias in meta analysis of the diagnostic accuracy of markers of bacterial infection. Clinical Infectious Dis- eases, 40, 1372-1373. doi:10.1086/429507
[35]
Whiting, P., Rutjes, A.W.S., Reitsma, J.B., et al. (2004) Sources of variation and bias in studies of diagnostic ac- curacy. Annals of Internal Medicine, 140, 189-202.
[36]
Hann, I., Viscoli, C., Paesmans, M., et al. (1997) A com- parison of outcome from febrile neutropenic episodes in children compared with adults, results from four EORTC studies. British Journal of Haematology, 99, 580-588.
doi:10.1046/j.1365-2141.1997.4453255.x
[37]
Albrich, W.C., Dusemund, F., Bucher, B., et al. (2012) Effectiveness and safety of procalcitonin-guided antibi- otic therapy in lower respiratory tract infections in “real life”. Archives of Internal Medicine, 172, 715-722.
doi:10.1001/archinternmed.2012.770
[38]
Hughes, W.T., Armstrong, D., Bodey, G.P., et al. (2002) Guidelines for the use of antimicrobial agents in neutron- penic patients with cancer. Clinical Infectious Diseases, 34, 730-751. doi:10.1086/339215
[39]
Link, H., Bohme, A., Cornely, O.A., et al. (2003) Antimi- crobial therapy of unexplained fever in neutropenic pa- tients—Guidelines of the infectious disease working par- ty of the german society of hematology and oncology. An- nals of Hematology, 82, S105-S117.
