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Chemotherapy Induced Neutropenia

Chemotherapy Induced Neutropenia – an Unmet Clinical Need

One of the major side effects of cancer chemotherapy is myelosuppression leading to an obligate period of neutropenia. Systemic infection resulting in neutropenic sepsis is the leading cause of morbidity and mortality in cancer patients. Due to these reasons chemotherapy induced neutropenia has been considered as an “oncologic emergency”.

Chemotherapy treatments for cancer are well- -known to Be associated with a depletion of white blood cells, in particular neutrophils, causing a condition known as chemotherapy- -induced neutropenia (CIN).

Where neutropenia is significant, it is associated with an increased risk of systemic infections that lead to sepsis and death [1,2,3,7,9].

Chemotherapy Induced Neutropenia

Neutropenia is a serious adverse effect frequently associated with cancer chemotherapy [1,7]. Loss of neutrophils causes disruption of immune defence mechanisms and increases the likelihood for infections. Infections lead to fever known as febrile neutropenia (FN). According to the European Society for Medical Oncology (ESMO), FN is defined by oral temperature greater than 38.5 °C for two consecutive readings within 2h and an absolute neutrophil count (ANC) below 0.5 x 109/ [1]. Neutrophils constitute the first line of defence against invading pathogens. Reduction of ANC leads to a predisposition to infection caused by bacteria and fungi [1,2].

Incidence, management strategies and impact

The incidence of FN can be as high as 50% in solid tumours and ≥80% in hematological malignancies [4,5]. Globally, the mortality rates associated with FN amongst cancer patients is extremely high ranging from 10-21% [4,8]. Chemotherapy- -induced neutropenia is the major cause for infection-related complications in cancer patients [4], including fungal infections, sepsis resulting from severe bacterimia, pneumonia and other respiratory tract infections, cerebrovascular disease and disorders of the liver and kidney [6,7].

The risk of death is further increased due to the presence of co-morbidities in the patients which poses an additional risk, these include patient specific characteristics such as age, type of malignancy, treatment regime, performance status, health and nutritional status and infectious complications [6,9].

In the current management if CIN occurs in the first few cycles of chemotherapy it results in significant dose reduction and delay in delivery of subsequent cycles, compromising effectiveness of treatment and disease-free/overall survival in patients treated with a curative intent [3,10,11]. Increasing age is associated with a higher risk of cancer. In addition, age also leads to reduced bone marrow reserve and compromised lung, kidney and liver functions, further increasing the risk of chemotherapy- -induced complications [3,11]. Other variables contributing to higher risk of developing neutropenia include the treatment regime, the chemotherapy drug or combination of drugs and associated toxicity [1,2].

 

References

  1. Lyman GH, CH Lyman, O Agboola (2005) Risk models for predicting chemotherapy- -induced neutropenia. Oncologist 10(6): 427-437.
  2. Lyman GH, NM Kuderer (2003) Epidemiology of febrile neutropenia. Support Cancer Ther 1(1): 23-35.
  3. Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult càncer patients. Cancer 106(10): 2258-2266.
  4. Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, et al., (2011) 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 47(1): 8-32.
  5. Aapro MS, Cameron DA, Pettengell R, Bohlius J, Crawford J, et al., (2006) 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 42(15): 2433-2453.
  6. Crawford J, DC Dale, GH Lyman (2004) Chemotherapy- -induced neutropenia: risks, consequences, and new directions for its management. Cancer 100(2): 228-237.
  7. Crawford J, Armitage J, Balducci L, Becker PS, Blayney DW, et al., (2013) Myeloid growth factors. J Natl Compr Canc Netw 11(10): 1266-1290.
  8. Wheatley JR, Kelly WT, Tully A, Engel LA (1991) Pressure- -diameter relationships of the upper airway in awake supine subjects. J Appl Physiol (1985) 70(5): 2242-2251.
  9. Dunbar Angela, Tai E, Nielsen DB, Shropshire S, Richardson LC (2014) Preventing Infections During Cancer Treatment: Development of an Interactive Patient Education Website. Clin J Oncol Nurs 18.4 (2014): 426- 431.
  10. Dale DC, McCarter GC, Crawford J, Lyman GH (2003) Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials. J Natl Compr Canc Netw 1(3): 440-454.
  11. Marshall E, H Innes (2008) Chemotherapy induced febrile neutropenia: management and prevention. Clin Med (Lond) 8(4): 448-451.