What Is Neutropenic Fever?

Neutropenic fever, also sometimes referred to as febrile neutropenia, is a form of fever that occurs in combination with a low white blood cell count. Specifically, neutrophils, a type of white blood cell that works to fight infections, are decreased in number in a neutropenic fever.

Usually, the people at risk for neutropenic fever are those with weakened immune systems from cancer treatments such as chemotherapy and hematopoietic stem cell transplantation. Other people at risk are those who are immunosuppressed as a result of an organ transplant or for treatment of an autoimmune disorder.

Definition

Neutrophils play an important role in the body as they are a type of immune cell that responds to bacterial and fungal infections. If there are low levels of neutrophils in the blood, then the body has a restricted ability to fight off infections.

In neutropenic fever, a person has both a low neutrophil count and a fever. Definitions used in neutropenic fever include:

• Neutropenia, or a low neutrophil level, is determined through blood tests and is defined as an absolute neutrophil count (ANC) lower than 500 cells per microliter (cells/µL) or an expected level that will fall below 500 cells/µL in the next 48 hours.
• Fever is a sustained temperature above 100.4 degrees Fahrenheit for at least one hour, or a single temperature reading above 101 degrees.

In people with a weakened immune system, neutropenic fever can be the sign of an infection. It is considered a medical emergency that requires prompt evaluation and treatment.

Signs and Symptoms of Neutropenic Fever

In addition to a fever, you may notice symptoms like chills, cough, sore throat, or fatigue. However, when the immune system is weakened, the normal signs of an infection may not always be present. As a result, a neutropenic fever may be one of the first signs that your body has an infection.

Causes and Risks

The first step in evaluation is to determine what may be causing the neutropenic fever, namely if it is the result of an infection or another cause, such as chemotherapy, medications that treat cancer. Chemotherapy can reduce your immune system’s ability to fight off infections and make these infections more serious.

In many cases, chemotherapy and stem-cell treatments for cancer can directly be linked to a neutropenic fever. During chemotherapy, neutrophil levels will naturally reach a low point around seven to 10 days following treatment.

Certain cancer treatments such as stem cell transplants and chimeric antigen receptor T-cell (CAR-T) therapy may also play a part in developing a neutropenic fever.

Diagnosis and Treatment of Neutropenic Fever

Diagnosis for neutropenic fever is established when there is a combination of a low neutrophil count and fever. The neutrophil count is determined as part of a complete blood count (CBC) with differential, which is a common blood test.

The treatment for neutropenic fever is predominantly focused on identifying and evaluating for potential causes such as chemotherapy vs. an infection. If your neutropenic fever is severe enough, you may receive treatment with antibiotics that have a broad spectrum of coverage for a variety of bacteria.

Blood tests to evaluate for bacteria and viruses can be used to help direct antibiotic treatment. Of note, however, blood tests are limited and can only identify a culprit organism in about 50% of people with a neutropenic fever.

Most of the bacteria that cause neutropenic fever are actually normal bacteria that live in the body and gut. When the immune system is weakened, bacteria from the gut can move across the mucosal surface of the gastrointestinal tract and into the bloodstream, where they cause a widespread infection.

Other common sources of infection are catheters and central lines that are used to deliver chemotherapy treatments into veins. If these central lines and catheters are left in the body for a long period of time, or if they are improperly cleaned, then bacteria that live on the skin can get inside the body.

In some cases, bacteria from the skin can travel into these catheters and throughout the bloodstream and cause a widespread infection. Fortunately, antibiotic treatments can help the body fight off these infections even if the immune system is weakened.

Select treatments aimed at supporting the function of the immune system are also used. The treatments, known as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to boost the immune system. Ryzneuta (efbemalenograstim alfa), Neupogen (filgrastim), and Neulasta (pegfilgrastim) are drugs that are based on G-CSF.

These colony-stimulating factor treatments promote the production of white blood cells in the bone marrow and work to increase the circulating levels of neutrophils and macrophages (another type of white blood cell).

In some cases, your healthcare provider may prescribe these colony-stimulating factors along with chemotherapy treatments to prevent neutropenic fever (prophylactic treatment).

Summary

Neutropenic fever is a fever, either sustained or spiked, in a patient who has a low white blood cell count. Cancer treatments such as chemotherapy and hematopoietic stem cell transplant (HSCT) are the most common causes of neutropenic fever. Bacterial infection may or may not be detected.

Treatment may include antibiotics. Drugs such as Neupogen and Neulasta that stimulate the production of white blood cells may be used.

A Word From Verywell

A neutropenic fever can occur at any time during the treatment for cancer and does not always indicate cancer is progressing or worsening. Identifying a neutropenic fever early and starting treatment can be a major help.