Skip to main content
SpringerLink
Log in

Myelosuppression

  • Chapter
  • First Online:
Pathobiology of Cancer Regimen-Related Toxicities

Abstract

Myelosuppression is the principal dose-limiting toxicity of cancer ­chemotherapy. Neutropenia, febrile neutropenia, and infections are the most important consequences. Cancer chemotherapy also causes anemia, thrombocytopenia, and immunodeficiency, but these are usually less severe complications. The risk and severity of myelosuppression is dependent on several factors including the tumor type (location, grade, and metastases), comorbidities, and the treatment regimen. Based on randomized clinical trials and broader clinical experience, several organizations have developed and regularly update treatment recommendations for optimal regimens and guidelines regarding strategies to avoid adverse effects including the risk of myelosuppression. Myeloid growth factors are now widely used to prevent chemotherapy-associated febrile neutropenia and facilitate the treatment of cancer.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
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

Similar content being viewed by others

References

  1. Zubrod CG, Schepartz SA, Carter SK. Historical background of the National Cancer Institute’s drug development thrust. Natl Cancer Inst Monogr. 1977;45:7–11.

    PubMed  Google Scholar 

  2. DeVita Jr VT, Chu E. A history of cancer chemotherapy. Cancer Res. 2008;68:8643–53.

    Article  PubMed  CAS  Google Scholar 

  3. Goodman LS, Wintrobe MM, Dameshek W, et al. Nitrogen mustard therapy. Use of methyl-bis(beta-chloroethyl)amine hydrochloride and tris(beta-chloroethyl)amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. JAMA. 1984;251:2255–61.

    Article  PubMed  CAS  Google Scholar 

  4. Farber S. Some observations on the effect of folic acid antagonists on acute leukemia and other forms of incurable cancer. Blood. 1949;4:160–7.

    PubMed  CAS  Google Scholar 

  5. Farber S, Diamond LK. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med. 1948;238:787–93.

    Article  PubMed  CAS  Google Scholar 

  6. DeVita Jr VT, Lewis BJ, Rozencweig M, et al. The chemotherapy of Hodgkin’s disease: past experiences and future directions. Cancer. 1978;42(2S):979–90.

    Article  PubMed  Google Scholar 

  7. Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist. 2005;10:427–37.

    Article  PubMed  Google Scholar 

  8. National Comprehensive Cancer Network. http://www.nccn.com/ (2012). Accessed 18 Feb 2012.

  9. MedlinePlus® (2012) Cancer Chemotherapy. US National Library of Medicine/NIH National Institutes of Health. http://www.nlm.nih.gov/medlineplus/cancerchemotherapy.html. Accessed 18 Feb 2012.

  10. Catlin SN, Busque L, Gale RE, et al. The replication rate of human hematopoietic stem cells in vivo. Blood. 2011;117:4460–6.

    Article  PubMed  CAS  Google Scholar 

  11. Mercier FE, Ragu C, Scadden DT. The bone marrow at the crossroads of blood and immunity. Nat Rev Immunol. 2011;12:49–60.

    Article  PubMed  Google Scholar 

  12. Hoggatt J, Pelus LM. Many mechanisms mediating mobilization: an alliterative review. Curr Opin Hematol. 2011;18:231–8.

    Article  PubMed  CAS  Google Scholar 

  13. Keating GM. Plerixafor: a review of its use in stem-cell mobilization in patients with lymphoma or multiple myeloma. Drugs. 2011;71:1623–47.

    Article  PubMed  CAS  Google Scholar 

  14. Demirer T, Buckner CD, Gooley T, et al. Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant. 1996;17:937–41.

    PubMed  CAS  Google Scholar 

  15. To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. Blood. 2011;118:4530–40.

    Article  PubMed  CAS  Google Scholar 

  16. Cronkite EP, Fliedner TM. Granulocytopoiesis. N Engl J Med. 1964;270:1403–8.

    Article  PubMed  CAS  Google Scholar 

  17. Perry S, Godwin HA, Zimmerman TS. Physiology of the granulocyte. 1. JAMA. 1968;203:937–44.

    Article  PubMed  CAS  Google Scholar 

  18. Dancey JT, Deubelbeiss KA, Harker LA, et al. Neutrophil kinetics in man. J Clin Invest. 1976;58:705–15.

    Article  PubMed  CAS  Google Scholar 

  19. Price TH, Chatta GS, Dale DC. Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans. Blood. 1996;88:335–40.

    PubMed  CAS  Google Scholar 

  20. Dale DC, Liles WC, Llewellyn C, et al. 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 

  21. Cartwright GE, Athens JW, Wintrobe MM. The kinetics of granulopoiesis in normal man. Blood. 1964;24:780–803.

    PubMed  CAS  Google Scholar 

  22. Dale DC, Fauci AS, Guerry IV D, et al. Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone. J Clin Invest. 1975;56:808–13.

    Article  PubMed  CAS  Google Scholar 

  23. Hansen PB, Knudsen LM, Johnsen HE, et al. Stimulation tests for the bone marrow neutrophil pool in malignancies. Leuk Lymphoma. 1995;16:237–46.

    Article  PubMed  CAS  Google Scholar 

  24. Hansen PB, Johnsen HE, Ralfkiaer E, et al. Blood neutrophil increment after a single injection of rhG-CSF or rhGM-CSF correlates with marrow cellularity and may predict the grade of neutropenia after chemotherapy. Br J Haematol. 1993;84:581–5.

    Article  PubMed  CAS  Google Scholar 

  25. Friberg LE, Henningsson A, Maas H, et al. Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J Clin Oncol. 2002;20:4713–21.

    Article  PubMed  Google Scholar 

  26. Hansson EK, Friberg LE. The shape of the myelosuppression time profile is related to the probability of developing neutropenic fever in patients with docetaxel-induced grade IV neutropenia. Cancer Chemother Pharmacol. 2012;69(4):881–90.

    Article  PubMed  CAS  Google Scholar 

  27. Athlin L, Domellöf L, Björkstén B. The effect of combination chemotherapy on neutrophil function in cancer patients. Cancer Lett. 1979;7:21–5.

    Article  PubMed  CAS  Google Scholar 

  28. Lejeune M, Ferster A, Cantinieaux B, et al. Prolonged but reversible neutrophil dysfunctions differentially sensitive to granulocyte colony-stimulating factor in children with acute lymphoblastic leukaemia. Br J Haematol. 1998;102:1284–91.

    Article  PubMed  CAS  Google Scholar 

  29. Lejeune M, Sariban E, Cantinieaux B, et al. Granulocyte functions in children with cancer are differentially sensitive to the toxic effect of chemotherapy. Pediatr Res. 1996;39:835–42.

    Article  PubMed  CAS  Google Scholar 

  30. Wijayahadi N, Haron MR, Stanslas J, et al. Changes in cellular immunity during chemotherapy for primary breast cancer with anthracycline regimens. J Chemother. 2007;19:716–23.

    PubMed  CAS  Google Scholar 

  31. Mendonça MA, Cunha FQ, Murta EF, et al. Failure of neutrophil chemotactic function in breast cancer patients treated with chemotherapy. Cancer. 2006;57:663–70.

    Google Scholar 

  32. Lower EE, Baughman RP. The effect of cancer and chemotherapy on monocyte function. J Clin Lab Immunol. 1990;31:121–5.

    PubMed  CAS  Google Scholar 

  33. Markowicz S, Walewski J, Zajda K, et al. Recovery of dendritic cell counts and function in peripheral blood of cancer patients after chemotherapy. Cytokines Cell Mol Ther. 2002;7:15–24.

    Article  PubMed  CAS  Google Scholar 

  34. Kondo M, Oshita F, Kato Y, et al. Early monocytopenia after chemotherapy as a risk factor for neutropenia. Am J Clin Oncol. 1999;22:103–5.

    Article  PubMed  CAS  Google Scholar 

  35. Thirumala R, Ramaswamy M, Chawla S. Diagnosis and management of infectious complications in critically ill patients with cancer. Crit Care Clin. 2010;26:59–91.

    Article  PubMed  CAS  Google Scholar 

  36. Hattangadi SM, Wong P, Zhang L, et al. From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications. Blood. 2011;118:6258–68.

    Article  PubMed  CAS  Google Scholar 

  37. Erslev AJ. Erythropoietin and anemia of cancer. Eur J Haematol. 2000;64:353–8.

    Article  PubMed  CAS  Google Scholar 

  38. Kuter DJ. The physiology of platelet production. Stem Cells. 1996;14 Suppl 1:88–101.

    Article  PubMed  Google Scholar 

  39. Sneed TB, Kantarjian HM, Talpaz M, et al. The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase. Cancer. 2004;100:116–21.

    Article  PubMed  CAS  Google Scholar 

  40. Ruchatz H, Puttini M, Cleris L, et al. Effect of imatinib on haematopoietic recovery following idarubicin exposure. Leukemia. 2003;17:298–304.

    Article  PubMed  CAS  Google Scholar 

  41. Zaucha JM, Wyrowinska E, Prejzner W, et al. Imatinib-associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia. Clin Lab Haematol. 2006;28:208–10.

    Article  PubMed  CAS  Google Scholar 

  42. O’Shaughnessy JA. Management of febrile neutropenia and cardiac toxicity in the adjuvant treatment of breast cancer. Clin Breast Cancer. 2007;8 Suppl 1:S11–21.

    Article  PubMed  Google Scholar 

  43. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and ­trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.

    Article  PubMed  CAS  Google Scholar 

  44. Servitja S, Ramos M, Gil M, et al. Multicenter, phase II, nonrandomized study of docetaxel plus trastuzumab every 21 days as the primary therapy in metastatic breast cancer overexpressing HER2. Anticancer Drugs. 2012;23:239–46.

    Article  PubMed  CAS  Google Scholar 

  45. Baselga J, Cortés J, Kim SB, et al. CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.

    Google Scholar 

  46. Wolach O, Bairey O, Lahav M. Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature. Medicine. 2010;89:308–18.

    Article  PubMed  Google Scholar 

  47. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47:8–32.

    Article  PubMed  CAS  Google Scholar 

  48. Gethins M. International cancer conference: targeted therapies boom expected in 3–5 years. J Natl Cancer Inst. 2011;103:1491–3.

    Article  PubMed  Google Scholar 

  49. Langer CJ. Individualized therapy for patients with non-small cell lung cancer: emerging trends and challenges. Crit Rev Oncol Hematol. 2012;83(1):130–44.

    Article  PubMed  Google Scholar 

  50. Kuderer NM, Lyman GH. Personalized medicine and cancer supportive care: appropriate use of colony-stimulating factor support of chemotherapy. J Natl Cancer Inst. 2011;103(12):910–3.

    Article  PubMed  Google Scholar 

  51. Page AV, Liles WC. Colony-stimulating factors in the prevention and management of infectious diseases. Infect Dis Clin North Am. 2011;25:803–17.

    Article  PubMed  Google Scholar 

  52. Lieschke GJ, Grail D, Hodgson G, et al. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood. 1994;84:1737–46.

    PubMed  CAS  Google Scholar 

  53. Liu F, Wu HY, Wesselschmidt R, et al. Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice. Immunity. 1996;5:491–501.

    Article  PubMed  CAS  Google Scholar 

  54. 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;325:164–70.

    Article  PubMed  CAS  Google Scholar 

  55. Cooper KL, Madan J, Whyte S, et al. Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer. 2011;11:404.

    Article  PubMed  CAS  Google Scholar 

  56. van Raam BJ, Drewniak A, Groenewold V, et al. Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3. Blood. 2008;112:2046–54.

    Article  PubMed  Google Scholar 

  57. Stanley E, Lieschke GJ, Grail D, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci U S A. 1994;91:5592–6.

    Article  PubMed  CAS  Google Scholar 

  58. Molineux G. The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr Pharm Des. 2004;10:1235–44.

    Article  PubMed  CAS  Google Scholar 

  59. Holmes FA, Jones SE, O’Shaughnessy J, et al. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol. 2002;13:903–9.

    Article  PubMed  CAS  Google Scholar 

  60. Green MD, Koelbl H, Baselga J, et al., International Pegfilgrastim 749 Study Group. 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.

    Google Scholar 

  61. Gravel P, Naik A, Le Cotonnec JY. Biosimilar rhG-CSFs: how similar are they? Target Oncol Suppl. 2012;1:3–16.

    Article  Google Scholar 

  62. Hartmann LC, Tschetter LK, Habermann TM, et al. Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia. N Engl J Med. 1997;336:1776–80.

    Article  PubMed  CAS  Google Scholar 

  63. Pérez Velasco R. Review of granulocyte colony-stimulating factors in the treatment of established febrile neutropenia. J Oncol Pharm Pract. 2011;17:225–32.

    Article  PubMed  Google Scholar 

  64. Glaspy J, Crawford J, Vansteenkiste J, et al. Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes. Br J Cancer. 2010;102:301–15.

    Article  PubMed  CAS  Google Scholar 

  65. Ludwig H, Aapro M, Bokemeyer C, et al. Treatment patterns and outcomes in the management of anaemia in cancer patients in Europe: findings from the Anaemia Cancer Treatment (ACT) study. Eur J Cancer. 2009;45:1603–15.

    Article  PubMed  Google Scholar 

  66. Vansteenkiste J, Glaspy J, Henry D, et al. Benefits and risks of using erythropoiesis-stimulating agents (ESAs) in lung cancer patients: study-level and patient-level meta-analyses. Lung Cancer. 2012;76(3):478–85.

    Article  PubMed  Google Scholar 

  67. Rizzo JD, Somerfield MR, Hagerty KL, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood. 2008;111:25–41.

    Article  PubMed  CAS  Google Scholar 

  68. Kuter DJ. New thrombopoietic growth factors. Clin Lymphoma Myeloma. 2009;9 Suppl 3:S347–56.

    Article  PubMed  CAS  Google Scholar 

  69. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377:393–402.

    Article  PubMed  CAS  Google Scholar 

  70. Cohn CS, Bussel JB. Romiplostim: a second-generation thrombopoietin agonist. Drugs Today. 2009;45:175–88.

    Article  PubMed  Google Scholar 

  71. Psaila B, Bussel JB, Linden MD, et al. In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation. Blood. 2012;119(17):4066–72.

    Article  PubMed  CAS  Google Scholar 

  72. Isaacs C, Robert NJ, Bailey FA, et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 1997;15:3368–77.

    PubMed  CAS  Google Scholar 

  73. Dorner AJ, Goldman SJ, Keith Jr JC. Interleukin-11. BioDrugs. 1997;8:18–29.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Washington, Seattle, WA, USA

    David C. Dale M.D.

Authors
  1. David C. Dale M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David C. Dale M.D. .

Editor information

Editors and Affiliations

  1. Brigham and Women’s Hospital, Francis Street 75, Boston, 01778, Massachusetts, USA

    Stephen T. Sonis

  2. Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, South Australia, Australia

    Dorothy M. Keefe

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Dale, D.C. (2013). Myelosuppression. In: Sonis, S., Keefe, D. (eds) Pathobiology of Cancer Regimen-Related Toxicities. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5438-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation