, Volume 30, Issue 9, pp 809–823 | Cite as

Costs Associated with Febrile Neutropenia in the US

  • Shannon L. MichelsEmail author
  • Rich L. Barron
  • Matthew W. Reynolds
  • Karen Smoyer Tomic
  • Jingbo Yu
  • Gary H. Lyman
Original Research Article


Background and Objective: Febrile neutropenia (FN) is a potentially life-threatening condition that may develop in cancer patients treated with myelosuppressive chemotherapy and result in considerable costs. This study was designed to estimate US healthcare utilization and costs in those experiencing FN by location of care, tumour type and mortality.

Methods: Cancer patients who received chemotherapy between 2001 and 2006 were identified from the HealthCore Integrated Research Database®, a longitudinal claims database with enrolment, medical, prescription and mortality information covering 12 health plans and more than 20 million US patients. Patients who experienced FN were prospectively matched using propensity score methods within each tumour type of interest (non-Hodgkin’s lymphoma, breast, lung, colorectal and ovarian cancer) to those not experiencing FN. Health resource utilization was compared per patient per month for unique prescriptions and visits (inpatient and outpatient) over the length of follow-up. Healthcare total paid costs adjusted to 2009 US dollars per patient per month were examined by FN group (FN vs non-FN, FN died vs FN survived), by source of care (physician office visit, outpatient services, hospitalization and prescriptions) and by tumour type. The number of unique FN-related encounters (inpatient and outpatient) and the number of patients experiencing at least one FN-related encounter were examined. The costs per encounter were tabulated. FN encounters differ from FN episodes in that a single FN episode may include multiple FN encounters (i.e. a patient is seen multiple times [encounters] for treatment of a single FN event [episode]).

Results: A total of 5990 patients each were successfully matched between the FN and non-FN (control) groups. Health resource utilization was generally higher in those with FN than in controls. FN patients incurred greater costs (mean ± SD: $US9628±12517 per patient-month) than non-FN patients ($US8478±12978). Chemotherapy comprised the majority of costs for both FN (33.5%) and non-FN (40.6%) patients. The largest cost difference by categorical source of care was for hospitalization (p<0.001). FN patients who died had the highest mean total costs compared with FN surviving patients ($US21 214 ± 25 596 per patient-month vs $US8227 ± 8850, respectively). Follow-up time for those surviving was, on average, 6.6 months longer. Hospitalization accounted for 53.1% of costs in those experiencing mortality with FN, while chemotherapy accounted for the majority of costs (37.1%) in surviving FN patients. A total of 6574 patients with at least one FN encounter experienced a total of 55 726 unique FN-related encounters, 90% of which were outpatient in nature. The majority of FN-related encounters (79%) occurred during the first chemotherapy course. The average costs for FN encounters were highest for inpatient encounters, $US22 086 ± 43 407, compared with $US985±1677 for outpatient encounters.

Conclusions: The occurrence of FN in cancer patients receiving chemotherapy results in greater healthcare resource utilization and costs, with FN patients who die accounting for the greatest healthcare costs. Most FN patients experience at least one outpatient FN encounter, and the total cost of treatment for FN continues to be high.


Propensity Score Febrile Neutropenia Healthcare Utilization Pegfilgrastim Outpatient Management 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The work reported here was funded by and performed for Amgen Inc. by the United BioSource Corporation. Shannon L. Michels was employed by United BioSource Corporation at the time of completion of this paper and is currently employed by Competitive Health Analytics Inc., a subsidiary of Humana. Matthew W. Reynolds works for the United BioSource Corporation, which performed this work under contract to Amgen Inc. Karen Smoyer Tomic and Jingbo Yu were employed by HealthCore, which received research funding from United BioSource Corporation and Amgen Inc. for conducting this study. Gary H. Lyman is a principal investigator on a research grant to the Duke Comprehensive Cancer Center at Duke University from Amgen Inc. Rich Barron is an employee of Amgen Inc.

Shannon L. Michels served as the principal investigator for the project, contributed to the study design and interpretation of the analysis, and drafted and revised the manuscript with input from all co-authors. Rich Barron contributed to the study design and interpretation of the analysis and assisted in drafting the manuscript. Matthew Reynolds contributed to the study design and interpretation of the analysis and reviewed and commented on/edited all drafts of the manuscript. Karen Smoyer Tomic contributed to the study design and interpretation of analysis, supervised the data extraction and analysis, and reviewed and commented on/edited all drafts of the manuscript. Jingbo Yu contributed to the study design and interpretation of analysis, performed the data extraction and analysis, and reviewed and commented on/edited all drafts of the manuscript. Gary H. Lyman contributed significantly to the study design and interpretation of analysis with expert knowledge in the field of oncology and assisted in drafting the manuscript. Shannon L. Michels can act as a guarantor for the overall content.


  1. 1.
    Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer 2004 Jan 15; 100(2): 228–37PubMedCrossRefGoogle Scholar
  2. 2.
    Kuderer NM, Dale DC, Crawford J, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 2006 May 15; 106(10): 2258–66PubMedCrossRefGoogle Scholar
  3. 3.
    Lyman GH, Kuderer NM. Epidemiology of febrile neutropenia. Support Cancer Ther 2003 Oct 1; 1(1): 23–35PubMedCrossRefGoogle Scholar
  4. 4.
    Pizzo PA. Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med 1993 May 6, 1993; 328(18): 1323–32Google Scholar
  5. 5.
    Crawford J, Dale DC, Kuderer NM, et al. Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. J Natl Compr Canc Netw 2008 Feb;6(2): 109–18PubMedGoogle Scholar
  6. 6.
    Lyman GH, Delgado DJ. Risk and timing of hospitalization for febrile neutropenia in patients receiving CHOP, CHOP-R, or CNOP chemotherapy for intermediate-grade non-Hodgkin lymphoma. Cancer 2003 Dec 1; 98(11): 2402–9PubMedCrossRefGoogle Scholar
  7. 7.
    Lyman GH, Morrison VA, Dale DC, et al. Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma 2003 Dec; 44(12): 2069–76PubMedCrossRefGoogle Scholar
  8. 8.
    Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist 2005 Jun–Jul; 10(6): 427–37PubMedCrossRefGoogle Scholar
  9. 9.
    Caggiano V, Weiss RV, Rickert TS, et al. Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 2005 May 1; 103(9): 1916–24PubMedCrossRefGoogle Scholar
  10. 10.
    Weycker D, Malin J, Edelsberg J, et al. Cost of neutropenic complications of chemotherapy. Ann Oncol 2008 Mar; 19(3): 454–60PubMedCrossRefGoogle Scholar
  11. 11.
    Elting LS, Lu C, Escalante CP, et al. Outcomes and cost of outpatient or inpatient management of 712 patients with febrile neutropenia. J Clin Oncol 2008 Feb 1; 26(4): 606–11PubMedCrossRefGoogle Scholar
  12. 12.
    Vogel CL, Wojtukiewicz MZ, Carroll RR, et al. First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol 2005 Feb 20; 23(6): 1178–84PubMedCrossRefGoogle Scholar
  13. 13.
    Lathia N, Mittmann N, DeAngelis C, et al. Evaluation of direct medical costs of hospitalization for febrile neutropenia. Cancer 2010 Feb 1; 116(3): 742–8PubMedCrossRefGoogle Scholar
  14. 14.
    Cosler LE, Sivasubramaniam V, Agboola O, et al. Effect of outpatient treatment of febrile neutropenia on the risk threshold for the use of CSF in patients with cancer treated with chemotherapy. Value Health 2005 Jan–Feb; 8(1): 47–52PubMedCrossRefGoogle Scholar
  15. 15.
    Trueman P. Prophylactic G-CSF in patients with early-stage breast cancer: a health economic review. Br J Cancer 2009 Sep; 101 Suppl. 1: S15–7PubMedCrossRefGoogle Scholar
  16. 16.
    Bennett CL, Calhoun EA. Evaluating the total costs of chemotherapy-induced febrile neutropenia: results from a pilot study with community oncology cancer patients. Oncologist 2007 Apr; 12(4): 478–83PubMedCrossRefGoogle Scholar
  17. 17.
    Stokes ME, Muehlenbein CE, Marciniak MD, et al. Neutropenia-related costs in patients treated with first-line chemotherapy for advanced non-small cell lung cancer. J Manag Care Pharm 2009 Oct; 15(8): 669–82PubMedGoogle Scholar
  18. 18.
    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 Sep; 14(9): 901–9PubMedCrossRefGoogle Scholar
  19. 19.
    Chang J. Chemotherapy dose reduction and delay in clinical practice. evaluating the risk to patient outcome in adjuvant chemotherapy for breast cancer. Eur J Cancer 2000 Apr; 36 Suppl. 1: S1 1–4Google Scholar
  20. 20.
    Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002 Mar 15; 34(6): 730–51PubMedCrossRefGoogle Scholar
  21. 21.
    Kuderer NM, Dale DC, Crawford J, et al. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol 2007 Jul 20; 25(21): 3158–67PubMedCrossRefGoogle Scholar
  22. 22.
    Clark OA, Lyman G, Castro AA, et al. Colony stimulating factors for chemotherapy induced febrile neutropenia. Cochrane Database Syst Rev 2003; (3): CD003039PubMedGoogle Scholar
  23. 23.
    Cosler LE, Eldar-Lissai A, Culakova E, et al. Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective. Pharmacoeconomics 2007; 25(4): 343–51PubMedCrossRefGoogle Scholar
  24. 24.
    Ozer H, Mirtsching B, Rader M, et al. Neutropenic events in community practices reduced by first and subsequent cycle pegfilgrastim use. Oncologist 2007 Apr; 12(4): 484–94PubMedCrossRefGoogle Scholar
  25. 25.
    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 Mar; 45(4): 608–17CrossRefGoogle Scholar
  26. 26.
    Elting LS, Rubenstein EB, Rolston KV, et al. Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials. Clin Infect Dis 1997 Aug; 25(2): 247–59PubMedCrossRefGoogle Scholar
  27. 27.
    Heckman J, Ichimura H, Todd P. Matching as an econometric evaluation estimator: evidence from evaluating a job training programme. Rev Econ Stud 1997; 64: 605–54CrossRefGoogle Scholar
  28. 28.
    Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983 Apr 1; 70(1): 41–55CrossRefGoogle Scholar
  29. 29.
    Rosenbaum P, Rubin D. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat 1985 Feb; 39(1): 33–8Google Scholar
  30. 30.
    Gold MR. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996Google Scholar
  31. 31.
    Efron B, Tibshirani R. An introduction to the bootstrap. New York: Chapman & Hall, 1993Google Scholar
  32. 32.
    Lyman GH, Michels SL, Reynolds MW, et al. Risk of mortality in patients with cancer who experience febrile neutropenia. Cancer 2010 Dec 1; 116(23): 5555–63PubMedCrossRefGoogle Scholar
  33. 33.
    Mayordomo JI, Lopez A, Vinolas N, et al. Retrospective cost analysis of management of febrile neutropenia in cancer patients in Spain. Curr Med Res Opin 2009 Oct; 25(10): 2533–42PubMedCrossRefGoogle Scholar
  34. 34.
    Segal BH, Freifeld AG, Baden LR, et al. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw 2008 Feb; 6(2): 122–74PubMedGoogle Scholar
  35. 35.
    Chen-Hardee S, Chrischilles EA, Voelker MD, et al. Population-based assessment of hospitalizations for neutropenia from chemotherapy in older adults with non-Hodgkin’s lymphoma (United States). Cancer Causes Control 2006 Jun; 17(5): 647–54PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Shannon L. Michels
    • 1
    Email author
  • Rich L. Barron
    • 2
  • Matthew W. Reynolds
    • 1
  • Karen Smoyer Tomic
    • 3
  • Jingbo Yu
    • 3
  • Gary H. Lyman
    • 4
  1. 1.United BioSource CorporationLexingtonUSA
  2. 2.Amgen Inc.Thousand OaksUSA
  3. 3.HealthCoreWilmingtonUSA
  4. 4.Duke University and the Duke Comprehensive Cancer CenterDurhamUSA

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