What Is Neutropenia
Neutrophils are a type of white blood cell that defend your body against bacteria. Chemotherapy, in addition to attacking tumor cells, damages the bone marrow where they are produced. When their levels drop significantly, this is called neutropenia, and your ability to fight off an infection is greatly reduced.
Not all cases of neutropenia cause symptoms. The problem arises when, in addition to having low neutrophil counts, you develop a fever: this is known as febrile neutropenia.
What Exactly Is Febrile Neutropenia?
The definition used by Spanish oncology is quite specific: febrile neutropenia is defined as an axillary temperature greater than 38.5°C for more than one hour, accompanied by an absolute neutrophil count of less than 500 mm³. Other hospital protocols use a slightly different threshold: an oral temperature of more than 38.3 °C, or two consecutive readings of more than 38.0 °C over a 2-hour period, along with a neutrophil count below 0.5 × 10⁹/L, or one that is expected to fall below that level within the next 48 hours. The exact figure may vary slightly depending on the hospital; what matters is the concept: fever + very low white blood cell count.
Why It’s a True Medical Emergency
This is not just a figure of speech. Neutropenic fever is a medical emergency that requires aggressive and early empirical treatment. Spanish emergency department guidelines are very clear on this point: broad-spectrum empirical antibiotic treatment should be initiated immediately after blood cultures are drawn, always within 60 minutes of the patient’s triage.
The reason is that, without neutrophils, an infection that would be mild in another person can progress very rapidly to sepsis. The mortality rate ranges from 4% to 30%, rising to as high as 70% if the correct empirical antibiotic treatment is not initiated early. With prompt and appropriate treatment, the vast majority of cases resolve favorably; that is why every minute counts.
When is it most likely to occur?
It does not occur at any point during the treatment cycle. Neutropenia reaches its nadir (lowest point) between 12 and 14 days after the first day of chemotherapy, and short-term neutropenia (less than 7 days) is expected in patients with solid tumors. In other words: the period of highest risk is usually around the second week after each cycle, not on the day of the infusion itself.
The microorganisms most commonly involved in severe infections are bacteria that normally live in the intestine: Gram-negative bacteria account for 30 to 50% of bacteremias and are the most common cause of severe febrile neutropenia, with the most frequent pathogens being Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa.
Signs to Watch For
The key symptom is fever, but the oncology team usually asks you to also watch for other warning signs related to low neutrophil counts:
- Fever (the main indicator).
- Fatigue. Unusual headaches.
- Chills, shivering, sore throat, cough, diarrhea, discomfort when urinating, or redness around the catheter or reservoir.
There is an important caveat: when neutrophil counts are very low, the body does not always react as it normally would. Most of these patients do not typically have an identifiable source of the fever or positive culture results, and the opacities characteristic of pneumonia may be atypical or even absent on the X-ray. This means there’s no need to wait for a clear diagnosis: a fever alone, in this context, is already reason enough to go to the emergency room.
What to Do If You Develop a Fever During Chemotherapy
- Take your temperature if you feel unwell, have chills, or feel feverish.
- Do not self-medicate. Before taking anything to lower your fever—including anti-inflammatory drugs or corticosteroids—consult your care team: some medications can mask the fever and delay diagnosis. Immunocompromised patients may not have a fever, and the fever may be masked by NSAIDs or corticosteroids.
- Call your hospital’s oncology/oncology emergency hotline (they usually provide this number when treatment begins) or go directly to the emergency room if the line is unavailable.
- Bring a report or note with you that includes your diagnosis, chemotherapy regimen, the date of your last cycle, and the medications you’re taking. This greatly speeds up the evaluation process.
- Don’t wait to see if it goes away on its own. Getting there early is what makes all the difference.
What Will Happen at the Hospital
In the ER, they’ll run blood tests to check your neutrophil count, perform blood cultures, and, if necessary, take a chest X-ray. The priority is to start broad-spectrum antibiotics as soon as possible: empirical antibiotic therapy should begin within the first hour after arrival at the ER, after samples have been taken for culture.
Not all cases require hospitalization. There are scales, such as the CISNE index, that help determine whether you can be treated on an outpatient basis with close monitoring or whether you need to be hospitalized; the medical team makes this decision based on your risk of complications—it’s not a choice you have to make on your own.
How to Prevent It: Growth Factors (G-CSF)
To prevent this from happening, many chemotherapy regimens are accompanied by granulocyte colony-stimulating factors (G-CSF), such as filgrastim or pegfilgrastim, which stimulate the bone marrow to produce more neutrophils. Primary prophylaxis with filgrastim, pegfilgrastim, or biosimilars is recommended when the probability of febrile neutropenia exceeds 20%; for intermediate risk (10–20%), the indication is determined on a case-by-case basis. Studies show that they work: the relative risk of febrile neutropenia with primary G-CSF prophylaxis compared to no prophylaxis was 0.51—meaning it reduces the risk by nearly half.
If your healthcare team has prescribed these injections, it’s important to follow the instructions on when to take them (your oncologist determines the dose and schedule). If they haven’t been prescribed, it doesn’t mean you’re unprotected: it depends on the specific treatment regimen and your individual risk.
In colon cancer, specifically
The risk of febrile neutropenia varies depending on the treatment regimen. With intensified three-drug chemotherapy for metastatic cancer (FOLFOXIRI), the risk is higher than with two-drug combinations such as FOLFOX or FOLFIRI: FOLFOXIRI/bevacizumab was associated with a higher incidence of neutropenia (51% vs. 21%) and febrile neutropenia (8% vs. 4%) than two-drug combinations. One reassuring finding from that same study: neither grade 3–4 neutropenia nor febrile neutropenia impaired treatment efficacy in terms of response, progression-free survival, or overall survival—in other words, if you experience these side effects, it does not mean the treatment will be less effective.
You’ll find more details about the effects of each regimen in the specific guidelines for FOLFOX, CAPOX, FOLFIRI, and bevacizumab on this website.
What Not to Do
- Don’t wait to see if the fever “goes away on its own” as the hours pass.
- Do not take anti-inflammatory drugs, aspirin, or corticosteroids on your own to lower your fever without first notifying the medical team.
- Don’t downplay other symptoms (diarrhea with a fever, pain when urinating, redness around the catheter): in this context, any sign of infection matters.
If, in addition to a fever, you have severe diarrhea, also consult our guide on chemotherapy-induced diarrhea, which explains when that symptom alone constitutes a medical emergency.