Chronic neutrophilic leukemia is an uncommon form of cancer that leads to the excessive production of a specific type of white blood cell called neutrophils. Neutrophils normally play an important role in the immune system by helping the body fight off infections. However, in CNL, the bone marrow, which is responsible for producing blood cells, starts creating too many neutrophils that don’t function properly.
CNL is classified as a type of blood cancer known as a myeloproliferative neoplasm. MPNs are a group of diseases that begin with abnormalities in stem cells within the bone marrow. In CNL, the overproduction of malfunctioning neutrophils can lead to complications like an enlarged liver or spleen, and in some cases, the disease may progress to a more severe form of cancer called acute leukemia.
A significant number of individuals with CNL have a certain genetic mutation called CSF3R T618I. This mutation is often found in the cells of individuals with the condition and is linked with the disease’s development.
CNL is considered a chronic condition, meaning it develops slowly over time. It is also quite uncommon, with only about 200 cases reported as of 2019. The exact number of people affected by CNL is unknown, but it typically affects individuals over age 66 and is slightly more common in men.
Symptoms
Chronic neutrophilic leukemia can sometimes develop without any noticeable signs, making it challenging to detect in its early stages. However, as the disease progresses and the number of neutrophils in the blood increases, various symptoms may begin to appear. Fatigue is a common sign, often leaving individuals feeling unusually tired or lacking energy. Some people may experience unexplained weight loss, which can be concerning.
Additionally, those with CNL might notice that they bruise more easily than usual, a sign that their blood’s ability to clot is affected. Bone pain, particularly in the limbs, is another symptom that can occur as the disease progresses. Night sweats, when individuals wake up drenched in sweat, can also be a distressing symptom.
As CNL advances, the spleen and liver may become enlarged. An enlarged spleen, located on the left side of the abdomen, can cause a feeling of fullness or discomfort in that area, even without eating a large meal. Similarly, an enlarged liver may also contribute to this sensation, further complicating the individual’s condition.
Causes
The exact cause of chronic neutrophilic leukemia remains unclear, but researchers have identified a strong link between the disease and a genetic mutation known as CSF3R. This mutation is commonly found in individuals with CNL and is believed to play a significant role in its development. In addition to CSF3R, other genetic alterations, like ASXL1, TET2, and SETBP1 are also doubted of contributing to the onset of CNL, although their precise roles are still being studied.
There may also be a connection between CNL and polycythemia vera, an uncommon blood disorder characterized by an increase in all kinds of blood cells. This potential association suggests that certain underlying conditions could influence the development of CNL.
Moreover, research indicates that up to 32 percent of individuals with CNL may experience issues with their plasma cells, further complicating the disease’s progression and highlighting the complex nature of CNL and its various contributing factors.
Diagnosis
The initial signs of CNL often include unexplained bruising or persistent fatigue. During a physical examination, a healthcare provider may also detect an enlarged spleen, which can be a key indicator of CNL. If these symptoms raise suspicion, the healthcare provider will likely order blood examinations and a bone marrow biopsy to further investigate.
To confirm the diagnosis, chromosome analysis is typically conducted to identify genetic alterations commonly associated with CNL, such as the CSF3R mutation. These genetic tests provide crucial information that helps in understanding the nature of the disease.
The diagnosis of CNL is made based on specific criteria established by the World Health Organization (WHO). These criteria guide healthcare providers in accurately detecting and determining CNL, ensuring that patients receive the appropriate treatment and care.
Treatment
There is no appropriate treatment for CNL due to its rarity, so healthcare providers typically focus on managing symptoms and slowing the over-creation of cells of white blood. Two commonly used medications for this purpose are interferon alpha and hydroxyurea.
Interferon alpha is another treatment option that helps manage CNL by overstimulating the immune system, which in turn slows down the production of white blood cells in the bone marrow. This medication can help regulate white blood cell counts in individuals with CNL, although its effectiveness can vary.
Hydroxyurea works by reducing the number of cells of white blood in the bloodstream and can also help shrink a swollen spleen, which is a common complication of CNL. However, it’s important to note that some individuals may eventually stop responding to hydroxyurea, even if it is initially effective.
In some cases, healthcare providers may suggest chemotherapy or targeted therapies to treat CNL. These options can include drugs like cladribine, thalidomide, ruxolitinib, and imatinib. However, the success of these treatments is variable, so they are not always the first choice.
Additionally, research is ongoing to explore treatments that specifically target the CSF3R gene alterations associated with CNL. These studies aim to develop more effective therapies tailored to the genetic characteristics of the disease.
When to consult a healthcare provider
You should consult a healthcare provider if you experience persistent symptoms like unexplained fatigue, frequent bruising, unexplained weight loss, night sweats, or a feeling of fullness in the left side of your abdomen, which could indicate an enlarged spleen. These symptoms may be subtle and develop gradually, but they can be signs of an underlying condition like chronic neutrophilic leukemia or other health issues. Early consultation with a healthcare provider is important for proper diagnosis and timely intervention, which can improve the effectiveness of treatment and overall outcomes.
Outlook
Individuals with chronic neutrophilic leukemia vary widely. The median survival time for those diagnosed with CNL is approximately 23.5 months, though survival can range anywhere from six months to over twenty years. The variability in outcomes underscores the need for continued research. An ongoing study on CNL is expected to significantly influence treatment approaches and potentially enhance outcomes for patients.
CNL is considered an aggressive type of leukemia and carries a risk of progressing to acute myeloid leukemia, a more serious kind of cancer that can affect red blood cells, white blood cells, and platelets. According to a review in 2015, about 10 to 20 percent of individuals with CNL experience this progression to AML. The time frame for this transformation is highly variable, ranging from 3 months to 94 months, with an average of around 21 months. This risk of transformation highlights the seriousness of CNL and the importance of careful monitoring and management.
Summary
Chronic neutrophilic leukemia is an uncommon blood cancer characterized by the excessive production of malfunctioning neutrophils, often linked to genetic alterations like CSF3R. Symptoms may include extreme tiredness, bruising, weight loss, and swollen liver or spleen. Diagnosis involves blood tests, bone marrow biopsy, and chromosome analysis. Treatment focuses on managing symptoms and may include medications like hydroxyurea and interferon alpha, though outcomes vary widely. CNL can progress to acute myeloid leukemia (AML) in some cases, with an average transformation time of 21 months. Ongoing research aims to improve treatment protocols and patient outcomes.
