- Prophylactic use of colony-stimulating factors (CSFs) to reduce the risk of febrile neutropenia is warranted when the risk of febrile neutropenia is approximately 20% or higher and no other equally effective and safe regimen that does not require CSFs is available.
- Primary prophylaxis is recommended for the prevention of febrile neutropenia in patients who are at high risk on the basis of age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen.
- Dose-dense regimens that require CSFs should be used only within an appropriately designed clinical trial or if supported by convincing efficacy data.
- Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death as a result of injury to other organs, include the prompt administration of CSFs.
Table 1. Patient Risk Factors for Febrile Neutropenia
In addition to chemotherapy regimen and type of malignancy, consider the following factors when estimating patient's overall risk of febrile neutropenia.
- Age ≥65 years
- Poor performance status or poor nutritional status
- Advanced disease
- Poor renal function
- Previous chemotherapy or radiation therapy
- Liver dysfunction, most notably elevated bilirubin
- Preexisting neutropenia or bone marrow involvement with tumor
- Cardiovascular disease
- Multiple comorbid conditions
- Open wounds or recent surgery
- HIV infection
Table 2. Patient Risk Factors for Poor Clinical Outcomes Resulting From Febrile Neutropenia or lnfection
- Sepsis syndrome
- Age >65 years
- Invasive fungal infection
- Profound neutropenia (absolute neutrophil count <0.1 × 109/L)
- Other clinically documented infections
- Hospitalization at time of fever
- Neutropenia expected to last >10 days
- Prior episode of febrile neutropenia
Treatment for Adult Patients
- Primary prophylaxis with a CSF starting with the first cycle and continuing through subsequent cycles of chemotherapy is recommended in patients who have an approximately 20% or higher risk for febrile neutropenia based on patient-, disease- and treatment-related factors. Primary CSF prophylaxis should also be administered in patients receiving dose-dense chemotherapy when considered appropriate. Consideration should be given to alternative, equally effective, and safe chemotherapy regimens not requiring CSF support when available. (Strong Recommendation; EB-B-H) (See Table 1)
- Secondary prophylaxis with a CSF is recommended for patients who experienced a neutropenic complication from a prior cycle of chemotherapy (for which primary prophylaxis was not received), in which a reduced dose or treatment delay may compromise disease-free or overall survival or treatment outcome. In many clinical situations, dose reduction or delay may be a reasonable alternative. (Strong Recommendation; EB-B-H)
- CSFs should not be routinely used for patients with neutropenia who are afebrile. (Strong Recommendation; EB-B-H)
- CSFs should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia. However, CSFs should be considered in patients with fever and neutropenia who are at high risk for infection-associated complications or who have prognostic factors predictive of poor clinical outcomes. (Strong Recommendation; EB-B-H) (See Table 2)
- Dose-dense regimens with CSF support should be used only if supported by convincing efficacy data or within an appropriately designed clinical trial. Efficacy data support the use of dose-dense chemotherapy in the adjuvant treatment of high-risk breast cancer and the use of high-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin in urothelial cancer. There are limited and conflicting data on the value of dose-dense regimens with CSF support in non-Hodgkin lymphoma, and it cannot routinely be recommended at this time. (Strong Recommendation; EB-B-H [for breast cancer and lymphoma]; Moderate Recommendation; EB-B-I [for urothelial cancer]).
- CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral-blood progenitor cells. Choice of mobilization strategy depends in part on type of cancer and type of transplantation. (Strong Recommendation; EB-B-H)
- CSFs should be administered after autologous stem-cell transplantation to reduce the duration of severe neutropenia.
(Strong Recommendation; EB-B-H)
- CSFs may be administered after allogeneic stem-cell
transplantation to reduce the duration of severe neutropenia.
(Weak Recommendation; EB-L).
- Prophylactic CSFs for patients with diffuse aggressive lymphoma age ≥ 65 years treated with curative chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) should be considered, particularly in the presence of comorbidities. (Moderate Recommendation; EB-B-I)
- Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia. The choice of agent depends on convenience, cost, and clinical situation. There have been no additional data comparing granulocyte CSFs and granulocyte-macrophage CSFs since the 2006 update. Therefore, there is no change in the recommendation regarding their therapeutic equivalency. (Strong Recommendation; EB-B-H)
- Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, include the prompt administration of CSFs or pegylated granulocyte CSFs. (Moderate Recommendation; FC [by others] B-I)
- The use of CSFs in pediatric patients will almost always be guided by clinical protocols. As in adults, the use of CSFs is reasonable as primary prophylaxis for pediatric patients with a high likelihood of febrile neutropenia. Similarly, the use of CSFs for secondary prophylaxis or for therapy should be limited to high-risk patients. (Strong Recommendation; EB-B-H)
- For pediatric indications in which dose-intense chemotherapy is known to have a survival benefit, such as Ewing sarcoma, CSFs should be used to enable the administration of these regimens. (Strong Recommendation; EB-B-H)
- CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection. (Moderate Recommendation; IC-I)