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Risk assessment of adults with chemotherapy-induced neutropenia

Author
Eric Bow, MD
Section Editor
Kieren A Marr, MD
Deputy Editor
Anna R Thorner, MD

INTRODUCTION

Cancer patients receiving systemic antineoplastic therapy sufficient to adversely affect myelopoiesis and the developmental integrity of the gastrointestinal mucosa are at risk for invasive infection due to colonizing bacteria and/or fungi that translocate across intestinal mucosal surfaces damaged by cytotoxic therapy. Since the magnitude of the neutrophil-mediated component of the inflammatory response may be muted in neutropenic patients [1], a fever may be the earliest and only sign of infection.

It is critical to recognize neutropenic fever early and to initiate empiric systemic antibacterial therapy promptly in order to avoid progression to a sepsis syndrome and possibly death. It is also important to assess the risk of serious complications in patients with neutropenic fever, since this assessment will dictate the approach to therapy, including the need for inpatient admission, intravenous antibiotics, and prolonged hospitalization [2].

This topic will provide an overview of the risk assessment for patients with neutropenic fever. An overview of neutropenic fever syndromes and the prevention and treatment of neutropenic fever syndromes in cancer patients at high and low risk for serious complications are presented separately; the diagnostic approach to patients presenting with neutropenic fever is also discussed elsewhere. (See "Overview of neutropenic fever syndromes" and "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults" and "Prophylaxis of invasive fungal infections in adults with hematologic malignancies" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients)" and "Treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications" and "Diagnostic approach to the adult presenting with neutropenic fever".)

DEFINITIONS

Fever — Fever in neutropenic patients is defined as a single oral temperature of >38.3°C (101°F) or a temperature of >38°C (100.4°F) sustained for >1 hour [2]. This is discussed in greater detail separately. (See "Overview of neutropenic fever syndromes", section on 'Definitions'.)

Neutropenia — The definition of neutropenia varies from institution to institution, but neutropenia is usually defined as an absolute neutrophil count (ANC) <1500 cells/microL and severe neutropenia as an ANC <500 cells/microL or an ANC that is expected to decrease to <500 cells/microL over the next 48 hours [2,3]. The risk of clinically important infection rises as the neutrophil count falls below 500 cells/microL and is higher in those with a prolonged duration of neutropenia (>7 days). For the purposes of this discussion, we are defining neutropenia as an ANC <500 cells/microL.

                      

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Literature review current through: Nov 2016. | This topic last updated: Tue Dec 08 00:00:00 GMT+00:00 2015.
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References
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  1. Sickles EA, Greene WH, Wiernik PH. Clinical presentation of infection in granulocytopenic patients. Arch Intern Med 1975; 135:715.
  2. Freifeld AG, Bow EJ, Sepkowitz KA, et al. 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:e56.
  3. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE). http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (Accessed on February 16, 2012).
  4. Bow EJ. The diagnostic approach to the febrile neutropaenic patient: Clinical considerations. In: Infections in Hematology, Maschmeyer G, Rolston K (Eds), Springer-Verlag, Heidelberg 2011.
  5. Fosså SD, Kaye SB, Mead GM, et al. Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom. J Clin Oncol 1998; 16:716.
  6. Tjan-Heijnen VC, Postmus PE, Ardizzoni A, et al. Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study. Ann Oncol 2001; 12:1359.
  7. Timmer-Bonte JN, de Boo TM, Smit HJ, et al. Prevention of chemotherapy-induced febrile neutropenia by prophylactic antibiotics plus or minus granulocyte colony-stimulating factor in small-cell lung cancer: a Dutch Randomized Phase III Study. J Clin Oncol 2005; 23:7974.
  8. Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist 2005; 10:427.
  9. Lyman GH, Dale DC, Friedberg J, et al. Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin's lymphoma: a nationwide study. J Clin Oncol 2004; 22:4302.
  10. Schwenkglenks M, Jackisch C, Constenla M, et al. Neutropenic event risk and impaired chemotherapy delivery in six European audits of breast cancer treatment. Support Care Cancer 2006; 14:901.
  11. Voog E, Bienvenu J, Warzocha K, et al. Factors that predict chemotherapy-induced myelosuppression in lymphoma patients: role of the tumor necrosis factor ligand-receptor system. J Clin Oncol 2000; 18:325.
  12. Intragumtornchai T, Sutheesophon J, Sutcharitchan P, Swasdikul D. A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma. Leuk Lymphoma 2000; 37:351.
  13. Ray-Coquard I, Borg C, Bachelot T, et al. Baseline and early lymphopenia predict for the risk of febrile neutropenia after chemotherapy. Br J Cancer 2003; 88:181.
  14. Blay JY, Chauvin F, Le Cesne A, et al. Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia. J Clin Oncol 1996; 14:636.
  15. Klastersky J, Paesmans M, Rubenstein EB, 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.
  16. Gianni L, Munzone E, Capri G, et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol 1995; 13:2688.
  17. von Minckwitz G, Schwenkglenks M, Skacel T, et al. Febrile neutropenia and related complications in breast cancer patients receiving pegfilgrastim primary prophylaxis versus current practice neutropaenia management: results from an integrated analysis. Eur J Cancer 2009; 45:608.
  18. Aapro MS, Cameron DA, Pettengell R, et al. EORTC guidelines for the use of granulocyte-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.
  19. Pettengell R, Schwenkglenks M, Leonard R, et al. Neutropenia occurrence and predictors of reduced chemotherapy delivery: results from the INC-EU prospective observational European neutropenia study. Support Care Cancer 2008; 16:1299.
  20. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2015; 33:3199.
  21. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related infections. Version 2.2014. http://www.nccn.org (Accessed on November 06, 2014).
  22. Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2013; 31:794.
  23. de Naurois J, Novitzky-Basso I, Gill MJ, et al. Management of febrile neutropenia: ESMO Clinical Practice Guidelines. Ann Oncol 2010; 21 Suppl 5:v252.
  24. Paesmans M, Klastersky J, Maertens J, et al. Predicting febrile neutropenic patients at low risk using the MASCC score: does bacteremia matter? Support Care Cancer 2011; 19:1001.
  25. Uys A, Rapoport BL, Anderson R. Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score. Support Care Cancer 2004; 12:555.
  26. Klastersky J, Paesmans M, Georgala A, et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin Oncol 2006; 24:4129.
  27. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296.
  28. Klastersky J, Paesmans M. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score: 10 years of use for identifying low-risk febrile neutropenic cancer patients. Support Care Cancer 2013; 21:1487.
  29. de Souza Viana L, Serufo JC, da Costa Rocha MO, et al. Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients. Support Care Cancer 2008; 16:841.
  30. Combariza JF, Lombana M, Pino LE, Arango M. C-reactive protein and the MASCC risk index identify high-risk patients with febrile neutropenia and hematologic neoplasms. Support Care Cancer 2015; 23:1009.
  31. Carmona-Bayonas A, Gómez J, González-Billalabeitia E, et al. Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients. Br J Cancer 2011; 105:612.
  32. Carmona-Bayonas A, Jiménez-Fonseca P, Virizuela Echaburu J, et al. Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study. J Clin Oncol 2015; 33:465.
  33. Sickles EA, Young VM, Greene WH, Wiernik PH. Pneumonia in acute leukemia. Ann Intern Med 1973; 79:528.
  34. Bell MS, Scullen P, McParlan D, et al. Neutropenic sepsis guidelines. Northern Ireland Cancer Network, Belfast 2010. p. 1-11.
  35. Vidal L, Paul M, Ben dor I, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials. J Antimicrob Chemother 2004; 54:29.
  36. Teuffel O, Ethier MC, Alibhai SM, et al. Outpatient management of cancer patients with febrile neutropenia: a systematic review and meta-analysis. Ann Oncol 2011; 22:2358.
  37. Vidal L, Paul M, Ben-Dor I, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev 2004; :CD003992.
  38. Schwaber MJ, Carmeli Y. Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 2007; 60:913.
  39. Kang CI, Chung DR, Ko KS, et al. Risk factors for infection and treatment outcome of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae bacteremia in patients with hematologic malignancy. Ann Hematol 2012; 91:115.
  40. Park CM, Koh Y, Jeon K, et al. Impact of Eastern Cooperative Oncology Group Performance Status on hospital mortality in critically ill patients. J Crit Care 2014; 29:409.
  41. Wright JD, Neugut AI, Ananth CV, et al. Deviations from guideline-based therapy for febrile neutropenia in cancer patients and their effect on outcomes. JAMA Intern Med 2013; 173:559.