The American Society of Clinical Oncology (ASCO) has released an updated version of its Clinical Practice Guidelines on the use of hematopoietic colony-stimulating factors (CSFs), a treatment option for neutropenia, which is a major complication of myelosuppressive chemotherapy.

The updates were based on a systematic review of randomized clinical trials, meta-analyses, and systematic reviews conducted between October 2005 and September 2014 and are intended to address the limitations and strengths of using CSFs in clinical practice.1

Key guideline recommendations include:

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• In patients with a greater than 20% risk of febrile neutropenia, primary prophylaxis with CSF with first and subsequent cycles of chemotherapy is recommended. The guidelines also note that regimens that do not require CSF and are equally effective should be considered as well.
• In patients with a neutropenic complication from a previous cycle of chemotherapy (without primary prophylaxis) and reduction or delay in treatment would alter outcome/survival, CSF is recommended for secondary prophylaxis. The authors note, however, that a reduction/delay may be reasonable in many situations.
• In patients with afebrile neutropenia, CSFs should not be used routinely.
• Adjunctive treatment of CSFs with antibiotics should not be routinely used for patients with febrile neutropenia. However, patients with febrile neutropenia who are considered at risk for poor outcomes or infection related-complications may be considered for adjunctive treatment with CSFs.
• The authors note that use of CSF with dose-dense regimens should only be considered when involved in a well-designed clinical trial or with support of convincing efficacy data.
• In order to mobilize peripheral-blood progenitor cells, CSFs may be used with plerixafor, after chemotherapy, or alone.
• To lessen the duration of severe neutropenia, CSFs should be given after autologous stem-cell transplants.
• To lessen the duration of severe neutropenia, CSFs may be given after allogeneic stem-cell transplants. Since the 2006 update, reports of increased risk of grade 2 to 4 graft-versus-host disease with CSF use after allogeneic transplantation have not been confirmed. The researchers note that the benefits seem to be modest with the limited amount of data.
• Patients age 65 or older, particularly those with comorbidities, with aggressive forms of diffuse lymphoma treated with curative chemotherapy should be considered for CSF prophylaxis.
• In pediatric patients, CSFs for primary prophylaxis is considered reasonable in patients at high risk for febrile neutropenia. Likewise, the guidelines note that secondary prophylaxis should be limited to patients who are high risk.
• CSFs should be used in pediatric patients to facilitate dose-intense chemotherapy regimens that are known to have survival benefits (Ewing sarcoma).
• The guidelines do not recommend using CSFs in nonrelapsed acute myeloid leukemia or nonrelapsed acute lymphocytic leukemia in pediatric patients without infection.
• There were no additional data to support a change in recommendation on treatment choice for treatment-related neutropenia. Patient’s clinical situation, convenience, and cost are factors considered in the agent choice.
• The authors note a moderate recommendation for use of CSFs or pegylated granulocyte CSFs in patients exposed to lethal doses of total-body radiotherapy without evidence of impending death from organ injury.

The authors highlight the evidence that comorbid conditions increase the risk of febrile neutropenia in patients treated with chemotherapy.

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Furthermore, when taking into account age and type of cancer, a patient’s comorbidities continue to be an important predictor for febrile neutropenia.

Finally, the authors note that granulocyte-CSFs are expensive and questions remain to be answered on cost effectiveness. However, it is emphasized that choice of agent should be guided by the clinical scenario, not cost.


  1. Smith T, Bohlke K, Lyman G, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol.  July 13, 2015. [epub ahead of print] doi: 10.1200/JCO.2015.62.3488.