SUMMARY: Neutropenia is a clinical challenge and its associated complications, such as febrile neutropenia and infection, are significant toxicities resulting from myelosuppressive chemotherapy. These complications necessitate immediate evaluation and treatment, frequently requiring empirical antibiotics and hospitalization. Hematopoietic Colony-Stimulating Factors (CSFs) are used to decrease the severity and duration of neutropenia and are recommended for patients at high risk of neutropenia due to chemotherapy regimens, age, or comorbidities, thereby reducing the risk of febrile neutropenia. Further, they are also utilized for stem-cell mobilization in transplantation (SCT). ASCO guidelines (updated in 2015) provided evidence-based guidance on the appropriate use of CSFs in adults receiving cancer treatment.
The present ASCO guideline update on use of hematopoietic Colony-Stimulating Factors (CSFs) in cancer patients was based on review of 33 randomized controlled trials and 16 meta-analyses, and systematic reviews, that addressed use of CSFs for the prevention or treatment of neutropenic events, published from September 1, 2014, to August 22, 2025.
Guideline Questions and Recommendations
Clinical Question: What factors should influence the decision to administer primary prophylaxis of febrile neutropenia with a CSF?
Recommendation:
1.1. Patients should be offered primary prophylaxis with a G-CSF when the risk of febrile neutropenia, secondary to a chemotherapy regimen, is equal to or greater than approximately 20%, unless an alternative chemotherapy regimen with comparable efficacy and safety that does not require G-CSF is available.
1.2. Among patients who receive chemotherapy with a lower risk of febrile neutropenia, primary prophylaxis with a G-CSF should be offered if a patient is at high risk of complications from febrile neutropenia based on age, comorbidities, or disease characteristics, and no alternative chemotherapy regimen with comparable efficacy and safety that does not require G-CSF is available.
1.3. If G-CSF is not affordable or available, antibiotic prophylaxis may be offered.
Qualifying statement for Recommendation 1.3: Antibiotic prophylaxis is not a preferred option due to the risk of antimicrobial resistance, disturbance of gut microbiome, Clostridioides difficile infection, and other adverse effects, which may outweigh the benefits of antibiotic use in many cases.
Clinical Question: What factors should influence the decision to administer secondary prophylaxis of febrile neutropenia with a CSF?
Recommendation:
2.1. Secondary prophylaxis with a CSF is recommended for patients who experienced a neutropenic complication from a previous cycle of chemotherapy (for which primary prophylaxis was not received), in which a reduced dose or treatment delay may compromise cure rates or survival outcomes. In many clinical situations, dose reduction or delay may be a reasonable alternative or additional strategy.
Clinical Question: Are there circumstances in which CSFs may be administered for the treatment of febrile neutropenia?
Recommendation:
3.1. A CSF should not be routinely used for patients with neutropenia who are afebrile.
3.2. A CSF should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia.
3.3. A CSF may be offered in patients with fever and neutropenia who are at high risk for infection-associated complications or who have prognostic factors that are predictive of poor clinical outcomes.
Clinical Question: What is the role of CSFs as adjuncts to progenitor-cell transplantation?
Recommendation:
4.1. A CSF should be used alone, after chemotherapy, or in combination with a CXCR4 inhibitor (Plerixafor or Motixafortide), to mobilize peripheral-blood progenitor cells. Choice of mobilization strategy depends in part on the type of cancer and type of transplantation.
4.2. A CSF should be administered after autologous SCT to reduce the duration of severe neutropenia.
4.3. A CSF may be administered after allogeneic SCT to reduce the duration of severe neutropenia.
Clinical Question: Should CSFs be avoided in patients receiving concomitant chemotherapy and radiation therapy?
Recommendation:
5.1. CSFs are not recommended in patients receiving concomitant chemotherapy and radiation therapy, particularly involving the mediastinum.
Note for Recommendation 5.1: There is little evidence regarding use of CSFs in patients receiving radiation therapy alone.
Clinical Question: Do CSFs differ in efficacy or safety?
Recommendation:
6.1. Filgrastim, Pegfilgrastim, Eflapegrastim, and biosimilars can be used for prophylaxis or treatment of febrile neutropenia. The choice of agent depends on cost, patient convenience, availability, accessibility, health system context, disease subtype, and treatment regimen.
The following factors increase the risk for Febrile Neutropenia in addition to chemotherapy regimen and type of malignancy
- Age 65 years or older or frailty based on geriatric assessment
- Advanced disease
- Previous chemotherapy or radiation therapy
- Preexisting neutropenia or bone marrow involvement with tumor
- Active or recent infection
- Colonization with multidrug-resistant organisms
- Open wounds or recent surgery
- Poor performance status
- Poor nutritional status or low BMI
- Poor renal function
- Liver dysfunction, most notably elevated bilirubin
- Cardiovascular disease
- HIV
- Multiple comorbid conditions
WBC Growth Factors: ASCO Guideline Update. Gyawali B, Bohlke K, Dickter JK, et al. J Clin Oncol. 2026; 44:812-824.
