4 Clinical Pearls for Granulocyte Colony Stimulating Factors (G-CSFs)

Neutropenia (an abnormally low number of granulocytes or neutrophils) is a common side effect of the cytotoxic chemotherapy used to treat many malignancies.

Unfortunately, there are a number of complications associated wth neutropenia. Most notably, a patient with neutropenia is less able to mount an immune response and is open to infections. In fact, neutropenic fever is a medical emergency. Untreated, it often progresses to sepsis, septic shock, and death. Furthermore, many patients undergoing chemotherapy are required to keep a central line in place to receive their medication. This places them at considerable risk for bloodstream infections.

To help prevent and treat neutropenia, we routinely use Granulocyte Colony Stimulating Factors (G-CSF) to patients undergoing myelosuppressive chemotherapy. Here are 4 clinical pearls for using G-CSFs.

1. Indications for G-CSF

In general, G-CSFs are indicated to either prevent or treat neutropenia. Although used most often in the setting of chemotherapy, they can also be used for patients with severe neutropenia outside of the oncological setting. Finally, G-CSFs are also used to "mobilize" hematopoietic progenitor cells to the peripheral circulation prior to a bone marrow transplant.

2. Differences in G-CSF Formulations

There are 6 formulations of G-CSF at the time of this writing (including 2 biosimilars). Here's a quick breakdown of the dosing for each.

• filgrastim [Neupogen]: 5 - 10 mcg/kg/day daily SubQ or IV
• filgrastim-sndz [Zarxio]: a biosimilar product for Neupogen. Also dosed at 5 - 10 mcg/kg/day daily SubQ or IV
• tbo-filgrastim [Granix]: another biosimilar for Neupogen. Also dosed at 5 - 10 mcg/kg/day daily SubQ or IV
• pegfilgrastim [Neulasta], [Neulasta Onpro]: 6 mg SubQ once per cycle of myelosuppressive chemotherapy.
• sargramostim [Leukine]: 250 mcg/m2/day daily SubQ or IV. Leukine is actually a GM-CSF (it stimulates both granulocytes and macrophages). It's primarily used in the setting of stem cell/bone marrow transplants, although it also has an indication for AML.

3. Timing and Duration of Therapy

G-CSFs are administered between 24-72 hours after receiving chemotherapy. The reason for this minimum 24-hour delay is to allow the body time to metabolize and excrete the cytotoxic drugs. Otherwise, there is a risk that enough chemotherapy will still be present in circulation to kill many of the neutrophils that are produced as a result of giving G-CSF.

Most G-CSFs are administered daily until neutrophil counts have recovered to at least 1000 cells/mm3. The package insert for filgrastim recommends treating for up to two weeks, or until counts have recovered to 10,000 cells/mm3 (whichever occurs first). The specific dosing depends on the indication for use. In the outpatient setting, it is much more common to administer peg-filgrastim (Neulasta). It is administered as a single 6mg subcutaneous injection. Only a single dose per cycle of chemotherapy is necessary. A newer formulation of peg-filgrastim, the Neulasta OnPro is another convenient option. This is an on-body injector that is placed on the patient immediately after receiving chemotherapy. It auto-injects itself 27 hours later, saving the patient another trip back to the infusion center. Of note, the patient cannot shower while wearing the OnPro.

4. Adverse Effects of G-CSF

Overall, G-CSFs are well tolerated. Although rare, there are a few serious adverse effects to monitor for. Patients must be monitored for splenic rupture. This often presents as left upper abdominal or shoulder pain. Splenic rupture can be fatal if left untreated. Patients may also rarely present with Acute Respiratory Distress Syndrome (ARDS), allergic reactions (including anaphylaxis), glomerulonephritis, capillary leak syndrome, and alveolar hemorrhage.

Nausea, pyrexia, dizziness, and rash are less serious (but more common) adverse effects to monitor for. Patients also may complain of bone pain as a result of treatment with G-CSFs. In many patients, this bone pain can be managed by administered PO antihistamines, such as loratadine.