Chronic neutrophilic leukemia (CNL) is a rare blood cancer affecting the bone marrow. It is a myeloproliferative neoplasm, a group of diseases defined by the overproduction of certain blood cells. In CNL, the bone marrow specifically produces an excessive number of mature white blood cells called neutrophils.
Neutrophils are part of the immune system that fights infections. The uncontrolled growth of these cells in CNL causes them to accumulate in the blood, bone marrow, spleen, and liver. This buildup disrupts normal blood cell production and function, leading to health problems.
Causes and Risk Factors
The primary cause of chronic neutrophilic leukemia is an acquired genetic mutation in the Colony-Stimulating Factor 3 Receptor (CSF3R) gene. This mutation is not inherited but occurs spontaneously in a bone marrow cell during a person’s life. The CSF3R gene’s protein controls neutrophil production, and the mutation causes this signaling process to become constantly active, leading to their overproduction.
The specific trigger for this mutation is unknown, but some factors are associated with a higher likelihood of developing CNL. The disease affects older adults, with an average diagnosis age of 66, and has a slight male predominance. These risk factors are statistical associations, as the disease’s development is traced back to the specific genetic change.
Symptoms and Complications
Many individuals with chronic neutrophilic leukemia initially have no symptoms, with the condition often discovered through routine blood tests. As the disease progresses, systemic issues can emerge from the body’s response to the cancer. These include:
- Persistent fatigue
- Unexplained weight loss
- Fever
- Night sweats
Patients often experience discomfort from an enlarged spleen and liver (hepatosplenomegaly), caused by the accumulation of excess neutrophils. This can lead to a feeling of fullness, bloating, or pain in the upper abdomen.
Other signs include bone pain from the expansion of bone marrow and easy bruising or bleeding due to abnormal platelet production. The formation of blood clots (thrombosis) is another potential complication resulting from the increased number and abnormal function of blood cells.
The Diagnostic Process
The diagnostic process for chronic neutrophilic leukemia begins with a complete blood count (CBC). This blood test reveals a persistently high number of neutrophils (neutrophilia) and may show other abnormalities like anemia or a low platelet count.
Because elevated neutrophil levels have many potential causes, doctors must first rule out more common conditions like chronic infections, inflammatory diseases, or other cancers.
A definitive diagnosis requires specialized testing. A bone marrow aspiration and biopsy are performed to confirm the overabundance of granulocytes. The most conclusive test is a molecular genetic analysis to detect the CSF3R mutation, a primary diagnostic criterion set by the World Health Organization (WHO).
Treatment Approaches
Due to its rarity, there is no single standard treatment for chronic neutrophilic leukemia. Goals include managing symptoms, lowering the neutrophil count, and reducing spleen and liver size. Plans are personalized based on a patient’s health, symptoms, and disease characteristics.
A common first-line therapy is the oral chemotherapy drug hydroxyurea, which decreases white blood cell production. Interferon-alfa is another medication that can slow blood cell production by engaging the immune system.
For patients with the CSF3R gene mutation, targeted therapies like ruxolitinib may be an option. These drugs inhibit the signaling pathways activated by the mutation. The long-term effectiveness of these medications is still under evaluation.
The only curative option for CNL is an allogeneic stem cell transplant, which replaces diseased bone marrow with healthy donor stem cells. This intensive procedure has significant risks and is considered only for younger, healthier patients with advanced disease.
Prognosis and Disease Management
The long-term outlook for individuals with chronic neutrophilic leukemia is variable. Prognosis depends on factors like the patient’s age, overall health, genetic features of the cancer, and treatment response. The median survival is estimated to be around 24 months.
CNL is a chronic condition requiring continuous management. Regular follow-up appointments with a hematologist are necessary to perform blood tests and monitor the disease’s status for any treatment adjustments.
A primary concern is the risk of CNL transforming into a more aggressive form of leukemia, such as acute myeloid leukemia (AML). This transformation occurs in a percentage of patients and impacts the prognosis. Medical supervision aims to control the disease in its chronic phase and monitor for signs of progression.