Chronic neutrophilic leukemia is a rare blood cancer characterized by the overproduction of mature neutrophils, a type of white blood cell. Currently, no standard treatment exists, but emerging research may offer new options.

Chronic neutrophilic leukemia (CNL) is a rare cancer that affects blood cells. It belongs to a group of disorders called myeloproliferative neoplasms.

In these disorders, your bone marrow makes too much of a certain type of blood cell. In the case of CNL specifically, your body produces too many neutrophils (a category of white blood cells).

CNL is very rare, with just over 200 cases reported. Its rarity has made it difficult to establish known risk factors or standard therapies. But researchers have identified a link to specific genetic mutations, particularly in the CSF3R gene.

CNL is a rare leukemia that progresses slowly. Early stages typically have no symptoms. As the disease advances, symptoms may develop.

Possible symptoms include:

These symptoms result from an abnormal increase in white blood cells, particularly neutrophils. This disrupts regular blood function.

Doctors may diagnose CNL using the World Health Organization (WHO) criteria for CNL diagnosis.

During a physical exam, the doctor may feel an enlarged spleen and order further tests to rule out other conditions.

These tests may include:

  • Complete blood count (CBC): A CBC measures the levels of different blood cells, looking for abnormally high white blood cell counts, especially neutrophils.
  • Bone marrow biopsy: Your doctor may extract a small sample of bone marrow and send it for examination under a microscope to check for abnormal cell production.
  • Genetic testing: Doctors look for mutations, especially in the CSF3R gene, which is often associated with CNL.

There’s no standard treatment for CNL, but doctors aim to manage symptoms and reduce the overproduction of white blood cells using specific medications.

Treatment options may include:

  • Hydroxyurea: This medication helps lower white blood cell counts and relieve symptoms. It’s often the first-line treatment.
  • Interferon alpha: This protein boosts your immune system, helping reduce the number of leukemia cells and slow disease progression.
  • Chemotherapy: Doctors don’t often recommend chemotherapy for people with CNL because it is unlikely to help and has strong side effects. However, it may be an option for people whose CNL is transforming into acute myeloid leukemia (AML).
  • Targeted therapy: Drugs like ruxolitinib (Jakafi) target specific genetic mutations, such as CSF3R, which are linked to the disease. However, researchers are still studying these therapies.
  • Stem cell transplant: Doctors may consider stem cell transplant as a potential treatment in young people or those with advanced disease. This procedure replaces the affected bone marrow with healthy stem cells to regenerate normal blood cell production.

Treatment plans are often personalized depending on the disease’s progression and the person’s needs, with regular blood tests to monitor response to treatment.

CNL is a rare and serious disease. A person’s outlook with this disease will depend on various factors, such as:

  • their age
  • their overall health
  • how early they receive a diagnosis

On average, life expectancy is about 2 years after diagnosis, though this depends on the response to treatment and the person’s overall health.

According to a 2020 paper, the 5-year overall survival rate for CNL ranged from 29% to 42%. Researchers note that all those who received stem cell transplants were still alive after 5 years, though they were all younger than age 65 years at the time of treatment.

Gene mutations, especially in CSF3R, and the effectiveness of treatment may also affect the outlook. Although recent advances in targeted therapies provide hope for better outcomes, the overall survival rate is still uncertain due to the disease’s rarity.

CNL typically progresses slowly but can lead to complications such as intracranial hemorrhage or AML.

The exact cause of CNL remains unknown. Most cases are linked to mutations in the CSF3R gene.

The CSF3R gene provides instructions for making a protein that controls the production and function of neutrophils. Mutations in this gene can cause uncontrolled growth of neutrophils.

The overproduction of neutrophils can cause splenomegaly and disrupt the production of other blood cells, which may lead to CNL.

Advancements in genetic research have also identified mutations in other genes that may lead to CNL, such as:

  • ASXL1
  • TET2
  • SETBP1

Researchers are still studying these mutations to understand their role in disease progression and potential treatment options.

Because of its rarity and the limited studies available, risk factors for CNL are not as well defined as they are for more common cancers or leukemias.

​​Some research suggests that CNL most commonly occurs in older adults, with the median age at diagnosis in the United States being age 70 to 73 years. People assigned male at birth may be at a slightly increased risk.

There are also no established environmental or lifestyle risk factors for CNL, making it difficult to predict who is more likely to develop the disease.

CNL is a rare but serious blood cancer that primarily affects older adults. It involves the overproduction of neutrophils due to genetic mutations, most often in the CSF3R gene.

The exact causes of CNL, including environmental or lifestyle factors, remain unclear. This is because the genetic mutations occur sporadically.

Early symptoms may not be noticeable, but timely diagnosis and treatment may improve quality of life and extend survival.