Risk Stratification in Febrile Neutropenic Patients



Febrile neutropenia is a common complication of antineoplastic chemotherapy, especially in patients with hematologic malignancies. Infection prevention strategies such as chemoprophylaxis or the administration of prophylactic growth factors have not been clearly shown to reduce complications of febrile neutropenia, to be cost-effective, or to have a significant impact on mortality. Since febrile neutropenic patients represent a heterogeneous population, extensive research has been conducted on how to reliably identify a low-risk subset and to develop risk-based treatment strategies for low-risk and non-low-risk subsets. For adult patients, two validated risk prediction models have been developed: the Talcott model and the MASCC risk index. Clinical criteria and the MASCC model have been used successfully to identify patients suitable for treatment with oral antimicrobial regimens, after early discharge from hospital or entirely as outpatients. The primary focus of risk assessment models has been the identification of patients at low risk for serious medical complications. Very little research has been conducted to try and identify intermediate-risk or high-risk patients. This area is open for further study.


Acute Myeloid Leukemia Chronic Myeloid Leukemia Hematologic Malignancy Febrile Neutropenia Medical Complication 
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  1. 1.
    Aapro MS, Cameron DA, Pettengell R, Bohlius J, Crawford J, Ellis M, et al. EORTC guidelines for the use of colony-stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer. 2006;42:2433–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Ameye L, Paesmans M, Aoun M, Thiel S, Jensenius JC. Severe infection is associated with lower M-ficolin concentration in patients with hematologic cancer undergoing chemotherapy. Abstract presented at the 12th International Symposium on Febrile Neutropenia, Luxemburg, Luxemburg, Mar 2010.Google Scholar
  3. 3.
    Baskaran ND, Gan GG, Adeeba K. Applying the multinational association for supportive care in cancer risk scoring in predicting outcome of febrile neutropenia patients in a cohort of patients. Ann Hematol. 2008;87:563–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Chamilos G, Bamias A, Efstathiou E, Zorzou PM, Kastritis E, Kostis E, et al. Outpatient treatment of low-risk neutropenic fever in cancer patients using oral moxifloxacin. Cancer. 2005;103:2629–35.Google Scholar
  5. 5.
    Cherif H, Johansson E, Björkholm M, Kalin M. The feasibility of early hospital discharge with oral antimicrobial therapy in low-risk patients with febrile neutropenia following chemotherapy for hematologic malignancies. Haematologica. 2006;91(2):215–22.PubMedGoogle Scholar
  6. 6.
    Cometta A, Calandra T, Gaya H, et al. Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto Infection Program. Antimicrob Agents Chemother. 1996;40:1108–15.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Cooper KL, Madan J, Whyte S, Stevenson MD, Akehurst RL. Granulocyte-colony stimulating factors for febrile neutropenia prophylaxis following chemotherapy : systematic review and meta-analysis. BMC Cancer. 2011;11:404.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    de Souza VL, Serufo JC, da Costa Rocha MO, Costa RN, Duarte RC. Performance of a modified MASCC index score for identifying low-risk febrile neutropenia cancer patients. Support Care Cancer. 2008;16:841–6.CrossRefGoogle Scholar
  9. 9.
    Elting LS, Lu C, Escalante CP, Giordano SH, Trent JC, Cooksley C, Avritscher BC, Tina Shih YC, Ensor J, Nebiyou Bekele B, Gralla RJ, Talcott JA, Rolston K. Outcomes and cost of outpatient or inpatient management of 712 patients with febrile neutropenia. J Clin Oncol. 2008;26:606–11.PubMedCrossRefGoogle Scholar
  10. 10.
    Feld R, Paesmans M, Freifeld AG, Klastersky J, Pizzo PA, Rolston KV, Rubenstein E, Talcott JA, Walsh TJ. Methodology for clinical trials involving patients with cancer who have febrile neutropenia : updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies. Clin Infect Dis. 2002;35:1463–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Finberg RW, Talcott JA. Fever and neutropenia : how to use a new treatment strategy. N Engl J Med. 1999;341:362–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Freifeld A, Marchigiani D, Walsh T, Chanock S, Lewis L, Hiemenz J, et al. A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during chemotherapy. New Engl J Med. 1999;341:305–11.PubMedCrossRefGoogle Scholar
  13. 13.
    Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:427–31.PubMedCrossRefGoogle Scholar
  14. 14.
    Gafter-Gvili A, Frase A, Paul M, Vidal L, Lawrie TA, van de Wetering MD, Kremer LCM, Leibovici L. Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database Syst Rev. 2012;(1):CD004386.Google Scholar
  15. 15.
    Girmenia C, Russo E, Carmosino I, Breccia M, Dragoni F, Latagliata R, Mecarocci S, Morano SG, Stefanizzi C, Alimena G. Early hospital discharge with oral antimicrobial therapy in patients with hematologic malignancies and low-risk febrile neutropenia. Ann Hematol. 2007;86:263–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Hendriks AM, Trice Loggers E, Talcott JA. Costs of home versus inpatient treatment for fever and neutropenia: analysis of a multicenter randomized trial. J Clin Oncol. 2011;29:3984–9.CrossRefGoogle Scholar
  17. 17.
    Hui EP, Leung LKS, Poon TCW, Mo F, Chan VTC, Ma ATW, Poon A, Hui EK, Mak S-s, Kenny ML, Lei KIK, Ma BBY, Mok TSK, Yeo W, Zee BCY, Chan ATC. Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network. Support Care Cancer. 2011;19:1625–35.PubMedCrossRefGoogle Scholar
  18. 18.
    Hughes WT, Amstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34:730–51.PubMedCrossRefGoogle Scholar
  19. 19.
    Innes HE, Smith DB, O’Reilly SM, Clark PI, Kelly V, Marshall E. 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. 2003;89:43–9.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Innes HE, Lim SL, Hall A, Chan SY, Bhalla N, Marshall E. Management of febrile neutropenia in solid tumors and lymphomas using the Multinational Association for Supportive Care in Cancer (MASCC) risk index: feasibility and safety in routine clinical practice. Support Care Cancer. 2008;16:485–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Kern WV, Cometta A, De Bock R, Langenaeken J, Paesmans M, Gaya H. Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. New Engl J Med. 1999;341:312–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Kern WV. Risk assessment and treatment of low-risk patients with febrile neutropenia. Clin Infect Dis. 2006;42:533–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Kern WV, Marchetti O, Drgona L, Akan H, Aoun M, Akova M, de Bock R, Paesmans M, Maertens J, Viscoli C, Calandra T. Oral moxifloxacin versus ciprofloxacin plus amoxicillin/clavulanic acid for low-risk febrile neutropenia – a prospective, double-blind, randomised, multicentre EORTC-Infectious Diseases Group (IDG) Trial (protocol 46001, IDG trial XV). 18th European Congress of Clinical Microbiology and Infectious Diseases, Barcelona, 2008.Google Scholar
  24. 24.
    Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, et al. The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18:3038–51.PubMedGoogle Scholar
  25. 25.
    Klastersky J. Management of patients with different risks of complication. Clin Infect Dis. 2004;39:S32–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Klastersky J, Paesmans M, Georgala A, Muanza F, Plehiers B, Dubreucq L, et al. Management with oral antibiotics in an outpatient setting of febrile neutropenic cancer patients selected on the basis of a score predictive for complications. J Clin Oncol. 2006;24:4129–34.PubMedCrossRefGoogle Scholar
  27. 27.
    Klastersky J, Ameye L, Maertens J, Georgala A, Muanza F, Aoun M, Ferrant A, Rapoport B, Rolston K, Paesmans M. Bacteremia in febrile neutropenic cancer patients. Int J Antimicrob Agents. 2007;30:51–9.CrossRefGoogle Scholar
  28. 28.
    Klastersky J, Paesmans M. Risk-adapted strategy for the management of febrile neutropenia in cancer patients. Support Care Cancer. 2007;15:477–82.PubMedCrossRefGoogle Scholar
  29. 29.
    Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106:2258–66.PubMedCrossRefGoogle Scholar
  30. 30.
    Leibovici D, Paul M, Cullen M, Bucaneve G, Gafter-Gvili A, Fraser A, Kern WV. Antibiotic prophylaxis in neutropenic patients: new evidence, practical decisions. Cancer. 2006;107:1743–51.PubMedCrossRefGoogle Scholar
  31. 31.
    Levenga TH, Timmer-Bonte JNH. Review of the value of colony stimulating factors for prophylaxis of febrile neutropenic episodes in adult patients treated for hematologic malignancies. Br J Haematol. 2007;138:146–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Moreau M, Klastersky J, Schwarzbold A, Muanza F, Georgala A, Aoun M, Loizidou A, Barette M, Costantini S, Delmelle M, Dubreucq L, Vekemans M, Ferrant A, Bron D, Paesmans M. A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematologic malignancies. Ann Oncol. 2009;20:513–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Paesmans M. Risk factors assessment in febrile neutropenia. Int J Antimicrob Agents. 2000;16:107–11.PubMedCrossRefGoogle Scholar
  34. 34.
    Paesmans M. Factors predictive for low and high risk of complications during febrile neutropenia and their implications for the choice of empirical therapy: experience of the MASCC Study Group on Infectious Diseases Abstract presented at the 6th International Symposium on Febrile Neutropenia – Brussels, Dec 2003.Google Scholar
  35. 35.
    Paesmans M for the MASCC study section on infectious diseases; the duration of febrile neutropenia. Abstract presented at the 8th International Symposium on Febrile Neutropenia, Athens, Jan 2006.Google Scholar
  36. 36.
    Paesmans M, Klastersky J, Maertens J, Georgala A, Muanza F, Aoun M, Ferrant A, Rapoport B, Rolston K, Ameye L. Predicting febrile neutropenia at low-risk using the MASCC score: does bacteremia matter? Support Care Cancer. 2011;19:1001–8Google Scholar
  37. 37.
    Park Y, Kim DS, Park SJ, Seo HY, Lee SR, Sung HJ, Park KH, Choi IK, Kim SJ, Oh SC, Seo JH, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS. The suggestion of a risk stratification system for febrile neutropenia patients with hematologic disease. Leuk Res. 2010;34:294–300.PubMedCrossRefGoogle Scholar
  38. 38.
    Rolston K, Rubenstein E, Elting L, Escalante C, Manzullo E, Bodey GP. Ambulatory management of febrile episodes in low-risk neutropenic patients (abstract LM 81). In: Program and Abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Washington DC, 2005.Google Scholar
  39. 39.
    Rolston KVI, Manzullo EF, Elting LS, Frisbee-Hume SE, McMahon L, Theriault RL, et al. Once daily, oral, outpatient quinolone monotherapy for low-risk cancer patients with fever and neutropenia. A pilot study for low-risk cancer patients with fever and neutropenia. Cancer. 2006;106:2489–94.PubMedCrossRefGoogle Scholar
  40. 40.
    Rolston KV, Frisbee-Hume SE, Patel S, et al. Oral moxifloxacin for outpatient treatment of low-risk, febrile neutropenic patients. Support Care Cancer. 2010;18:89–94.PubMedCrossRefGoogle Scholar
  41. 41.
    Rubenstein EB, Rolston K, Benjamin RS, Loewy J, Escalante C, Manzullo E, et al. Outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. Cancer. 1993;71:3640–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Sebban C, Dussart S, Fuhrmann C, Ghesquières H, Rodrigues I, Geoffrois L, Devaux Y, Lancry L, Chvetzoff G, Bachelot T, Chelghoum M, Biron P. Oral moxifloxacin or intravenous ceftriaxone for the treatment of low-risk neutropenic fever in cancer patients suitable for early hospital discharge. Support Care Cancer. 2008;16:1017–23.PubMedCrossRefGoogle Scholar
  43. 43.
    Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, et al. Update of Recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–205.PubMedCrossRefGoogle Scholar
  44. 44.
    Talcott JA, Finberg R, Mayer RJ, Goldman L. The medical course of patients with fever and neutropenia: clinical identification of a low-risk subgroup at presentation. Arch Intern Med. 1988;148:2561–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Talcott JA, Siegel RD, Finberg R, Goldman L. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol. 1992;10:316–22.PubMedGoogle Scholar
  46. 46.
    Talcott JA, Yeap BY, Clark JA, Siegel RD, Trice Loggers E, Lu C, Godley PA. Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial. J Clin Oncol. 2011;29:3977–83.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Teuffel O, Amir E, Alibhai S, Beyene J, Shung L. Cost effectiveness of outpatient treatment for febrile neutropenia in adult cancer patients. Br J Cancer. 2011;104:1377–83.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Uys A, Rapoport BL, Anderson R. Febrile neutropenia: a prospective study to validate the Multniational Association for Supportive Care in Cancer (MASCC) risk-index score. Support Care Cancer. 2004;12:555–60.PubMedCrossRefGoogle Scholar
  49. 49.
    Uys A, Rapoport BL, Fickl H, Meyer PWA, Anderson R. Prediction of outcome in cancer patients with febrile neutropenia: comparison of the Multinational Association of Supportive Care in Cancer risk-index score with procalcitonin, C-reactive protein, serum amyloid A, and interleukins-1β, -6, -8 and -10. Eur J Cancer. 2007;16:475–83.CrossRefGoogle Scholar
  50. 50.
    Vento S, Cainelli F. Infections in patients with cancer undergoing chemotherapy: aetiology, prevention and treatment. Lancet Oncol. 2003;4:595–604.PubMedCrossRefGoogle Scholar
  51. 51.
    Vidal L, Paul M, Ben dor I, Soares-Weiser K, Leibovici L. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials. JAC. 2004;54:29–37.PubMedGoogle Scholar
  52. 52.
    Weycker D, Malin J, Edelsberg J, Glass A, Gokhale M, Oster G. Cost of neutropenic complications of chemotherapy. Ann Oncol. 2008;19:454–60.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Data Centre – Institut Jules BordetBrusselsBelgium

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