Skip to main content
SpringerLink
Log in

Neutropenia and the Problem of Fever and Infection in Patients With Cancer

  • Chapter
Hematopoietic Growth Factors in Oncology

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 166 Accesses

Abstract

The role of blood neutrophils in the defense against infections is well recognized. A deficiency of neutrophils, or neutropenia, defined as an absolute neutrophil count (ANC) < 1.5 × 109/L, limits the rate at which neutrophils can accumulate at a site of tissue injury or infection. Chemotherapy can cause neutropenia and ultimately affect this defense mechanism. With severe neutropenia (an ANC < 0.5 × 109/L) the risk of serious infections increases substantially.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Blackwell S, Crawford J. Filgrastim (r-metHuG-CSF) in the chemotherapy setting. In: Morstyn G, Dexter T, eds., Filgrastim (r-metHuG-CSF) in Clinical Practice. New York: Marcel Dekker. 1994; 103–116.

    Google Scholar 

  2. 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; 34: 730–751.

    Article  PubMed  Google Scholar 

  3. Dale DC, McCarter GC, Crawford J et al. Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials. J Nall Coop Cancer Network 2003; 1: 440 154.

    Google Scholar 

  4. 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: 316–322.

    PubMed  CAS  Google Scholar 

  5. Lyman GH, Dale DC, Crawford J, Stolshek B, Carter W, Delgado D. Risk of febrile neutropenia among patients receiving CHOP chemotherapy. Blood 2001; 98:231b, abstract 4642.

    Google Scholar 

  6. Lyman GH, Kuderer NM, Djulbegovic B. Prophylactic granulocyte colony-stimulating factor in patients receiving dose-intensive cancer chemotherapy: a meta-analysis. Am J Med 2002b; 112: 406–411.

    Article  PubMed  CAS  Google Scholar 

  7. Silber JH, Fridman M, DiPaola RS, Erder MH, Pauly MV, Fox KR. First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy. J Clin Oncol 1998; 16: 2392–2400.

    PubMed  CAS  Google Scholar 

  8. Rivera E, Erder MH, Moore TD, et al. Targeted filgrastim support in early-stage breast cancer: towards the implementation of a risk model. Cancer 2003; 98: 222–228.

    Article  PubMed  Google Scholar 

  9. Agboola O, Crawford J, Dale DC, et al. Risk models for neutropenic complications associated with breast cancer adjuvant chemotherapy. Proc Am Soc Clin Oncol 2002; 21:66a, abstract 261.

    Google Scholar 

  10. Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 1991; 325: 164–170.

    Article  PubMed  CAS  Google Scholar 

  11. Chatta GS, Price TH, Allen RC, Dale DC. Effects of in vivo recombinant methionyl granulocyte colony-stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers. Blood 1994; 84: 2923–2929.

    PubMed  CAS  Google Scholar 

  12. Egusa Y, Fujiwara Y, Syaharuddin E, Sumiyoshi H, Isobe T, Yamakido M. Mobilization of peripheral blood stem cells in patients with advanced thoracic malignancies after irinotecan (CPT-11) administration. Anticancer Res 1998; 18: 481–488.

    PubMed  CAS  Google Scholar 

  13. Zinner SH. Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on gram-positive and resistant bacteria. Clin Infect Dis 1999; 29: 490–494.

    Article  PubMed  CAS  Google Scholar 

  14. McNeil MM, Nash SL, Hajjeh RA, et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 2001; 33: 641–647.

    Article  PubMed  CAS  Google Scholar 

  15. De Pauw BE. Practical modalities for prevention of fungal infections in cancer patients. Eur J Clin Microbiol Infect Dis 1997; 16: 32–41.

    Article  PubMed  Google Scholar 

  16. Singh N. Trends in the epidemiology of opportunistic fungal infections: predisposing factors and the impact of antimicrobial use practices. Clin Infect Dis 2001; 33: 1692–1696.

    Article  PubMed  CAS  Google Scholar 

  17. Rex JH, Walsh TJ, Anaissie EJ. Fungal infections in iatrogenically compromised hosts. Adv Intern Med 1998; 43: 321–371.

    PubMed  CAS  Google Scholar 

  18. Hachem R, Raad I. Prevention and management of long-term catheter related infections in cancer patients. Cancer Invest 2002; 20: 1105–1113.

    Article  PubMed  Google Scholar 

  19. Nagata S, Tsuchiya M, Asano S, et al. Molecular cloning and expression of cDNA for human granulocyte colony stimulating factor. Nature 1986; 319: 415–418.

    Article  PubMed  CAS  Google Scholar 

  20. Souza LM, Boone TC, Gabrilove J, et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 1986; 232: 61–65.

    Article  PubMed  CAS  Google Scholar 

  21. Kawakami M, Tsutsumi H, Kumakawa T, et al. Levels of serum granulocyte colony-stimulating factor in patients with infections. Blood 1990; 76: 1962–1964.

    PubMed  CAS  Google Scholar 

  22. Cheers C, Haigh AM, Kelso A, Metcalf D, Stanley ER, Young AM. Production of colony-stimulating factors (CSFs) during infection: separate determinations of macrophage-, granulocyte-, granulocyte-macrophage-, and multi-CSFs. Infect Immun 1988; 56: 247–251.

    PubMed  CAS  Google Scholar 

  23. Hammond WP, Csiba E, Canin A, et al. Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor. J Clin Invest 1991; 87: 704–710.

    Article  PubMed  CAS  Google Scholar 

  24. Selig C, Nothdurft W. Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections. Infect Immun 1995; 63: 104–109.

    PubMed  CAS  Google Scholar 

  25. Cebon J, Layton JE, Maher D, Morstyn G. Endogenous haemopoietic growth factors in neutropenia and infection. Br J Haematol 1994; 86: 265–274.

    Article  PubMed  CAS  Google Scholar 

  26. Begley CG, Lopez AF, Nicola NA, et al. Purified colony-stimulating factors enhance the survival of human neutrophils and eosinophils in vitro: a rapid and sensitive microassay for colony-stimulating factors. Blood 1986; 68: 162–166.

    PubMed  CAS  Google Scholar 

  27. Dale DC, Liles WC, Llewellyn C, Price TH. Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil kinetics and function in normal human volunteers. Am J Hematol 1998; 57: 7–15.

    Article  PubMed  CAS  Google Scholar 

  28. Price TH, Chatta GS, Dale DC. Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans. Blood 1996; 88: 335–340.

    PubMed  CAS  Google Scholar 

  29. Hubel K, Dale DC, Liles WC. Therapeutic use of cytokines to modulate phagocyte function for the treatment of infectious diseases: current status of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and interferon-gamma. J Infect Dis 2002; 185: 1490–1501.

    Article  PubMed  CAS  Google Scholar 

  30. Dale DC. Colony-stimulating factors for the management of neutropenia in cancer patients. Drugs 2002; 62: 1–15.

    Article  PubMed  CAS  Google Scholar 

  31. Milkovich G, Moleski RJ, Reitan JF, et al. Comparative safety of filgrastim versus sargramostim in patients receiving myelosuppressive chemotherapy. Pharmacotherapy 2000; 20: 1432–1440.

    Article  PubMed  CAS  Google Scholar 

  32. Garcia-Carbonero R, Mayordomo JI, Tornamira MV, et al. Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial. J Natl Cancer Inst 2001; 93: 31–38.

    Article  PubMed  CAS  Google Scholar 

  33. Anaissie EJ, Vartivarian S, Bodey GP, et al. Randomized comparison between antibiotics alone and antibiotics plus granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) in cancer patients with fever and neutropenia. Am J Med 1996; 100: 17–23.

    Article  PubMed  CAS  Google Scholar 

  34. Vellenga E, Uyl-de Groot CA, de Wit R, et al. Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia. J Clin Oncol 1996; 14: 619–627.

    PubMed  CAS  Google Scholar 

  35. Mayordomo JI, Rivera F, Diaz-Puente MT, et al. Improving treatment of chemotherapy-induced neutropenic fever by administration of colony-stimulating factors. J Natl Cancer Inst 1995; 87: 803–808.

    Article  PubMed  CAS  Google Scholar 

  36. Maher DW, Lieschke GJ, Green M, et al. Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial. Ann Intern Med 1994; 121: 492–501.

    PubMed  CAS  Google Scholar 

  37. Riikonen P, Saarinen UM, Makipernaa A, et al. Recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of febrile neutropenia: a double blind placebo-controlled study in children. Pediatr Infect Dis J 1994; 13: 197–202.

    Article  PubMed  CAS  Google Scholar 

  38. Wallam M, Agboola Y, Lyman G. Meta-analysis of colony-stimulating factors to treat febrile neutropenia (FN) in patients receiving cancer chemotherapy. Proc ASCO 2001; 2: 306b.

    Google Scholar 

  39. Green MD, Koelbl H, Baselga J, et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003; 14: 29–35.

    Article  PubMed  CAS  Google Scholar 

  40. Holmes FA, O’Shaughnessy JA, Vukelja S, et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 2002; 20: 727–731.

    Article  PubMed  CAS  Google Scholar 

  41. Engels EA, Lau J, Barza M. Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis. J Clin Oncol 1998; 16: 1179–1187.

    PubMed  CAS  Google Scholar 

  42. Rotstein C, Mandell LA, Goldberg N. Fluoroquinolone prophylaxis for profoundly neutropenic cancer patients: a meta-analysis. Curr Opin Oncol 1997; 4: S2–7.

    Google Scholar 

  43. Cruciani M, Rampazzo R, Malena M, et al. Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis 1996; 23: 795–805.

    Article  PubMed  CAS  Google Scholar 

  44. Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 3: 319–324.

    Article  Google Scholar 

  45. Weaver CH, Schulman KA, Wilson-Relyea B, Birch R, West W, Buckner CD. Randomized trial of filgrastim, sargramostim, or sequential sargramostim and filgrastim after myelosuppressive chemotherapy for the harvesting of peripheral-blood stem cells. J Clin Oncol 2000; 18: 43–53.

    PubMed  CAS  Google Scholar 

  46. Yau JC, Neidhart JA, Triozzi P, et al. Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating-factor support for dose-intensive cyclophosphamide, etoposide, and cisplatin. Am J Hematol 1996; 51: 289–295.

    Article  PubMed  CAS  Google Scholar 

  47. Bajorin DF, Nichols CR, Schmoll HJ, et al. Recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to conventional-dose ifosfamide-based chemotherapy for patients with advanced or relapsed germ cell tumors: a randomized trial. J Clin Oncol 1995; 13: 79–86.

    PubMed  CAS  Google Scholar 

  48. Bunn PA, Jr, Crowley J, Kelly K, et al. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 1995; 13: 1632–1641.

    PubMed  Google Scholar 

  49. Zinzani PL, Pavone E, Storti S, et al. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin’s lymphoma. Blood 1997; 89: 3974–3979.

    PubMed  CAS  Google Scholar 

  50. Chevallier B, Chollet P, Merrouche Y, et al. Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer. J Clin Oncol 1995; 13: 1564–1571.

    PubMed  CAS  Google Scholar 

  51. Pettengell R, Gurney H, Radford JA, et al. Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood 1992; 80: 1430–1436.

    PubMed  CAS  Google Scholar 

  52. Messori A, Trippoli S, Tendi E. G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation. J Clin Pharm Ther 1996; 21: 57–63.

    Article  PubMed  CAS  Google Scholar 

  53. Meropol NJ, Miller LL, Korn EL, Braitman LE, MacDermott ML, Schuchter LM. Severe myelosuppression resulting from concurrent administration of granulocyte colony-stimulating factor and cytotoxic chemotherapy. J Nati Cancer Inst 1992; 84: 1201–1203.

    Article  CAS  Google Scholar 

  54. Ozer H, Armitage JO, Bennett CL, et al. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel. J Clin Oncol 2000; 18: 3558–3585.

    PubMed  CAS  Google Scholar 

  55. Crawford J, Kreisman H, Garewal H, et al. The impact of filgrastim schedule variation on hematopoietic recovery post-chemotherapy. Ann Oncol 1997; 8: 1117–1124.

    Article  PubMed  CAS  Google Scholar 

  56. Koumakis G, Vassilomanolakis M, Barbounis V, et al. Optimal timing (preemptive versus supportive) of granulocyte colony-stimulating factor administration following high-dose cyclophosphamide. Oncology 1999; 56: 28–35.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. David C. Dale MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Amgen, Australia, Pty. Ltd., Monash University, Victoria, Australia

    George Morstyn MBBS, PhD, FRACP

  2. Amgen Inc., Thousand Oaks, CA, USA

    MaryAnn Foote PhD

  3. Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Melbourne, Australia

    Graham J. Lieschke MBBS, PhD, FRACP

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Dale, D.C. (2004). Neutropenia and the Problem of Fever and Infection in Patients With Cancer. In: Morstyn, G., Foote, M., Lieschke, G.J. (eds) Hematopoietic Growth Factors in Oncology. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-747-5_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-747-5_11

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9847-9

  • Online ISBN: 978-1-59259-747-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation