Chronic neutrophilic leukemia

Chronic Neutrophilic Leukemia

Chronic Neutrophilic Leukemia (CNL) is a rare myeloproliferative neoplasm characterized by the overproduction of neutrophils, a type of white blood cell. It is a clonal disorder of the hematopoietic stem cells and is classified under the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia.

Clinical Presentation

Patients with CNL often present with symptoms related to splenomegaly, such as abdominal discomfort or fullness. Other symptoms may include fatigue, weight loss, and night sweats. Laboratory findings typically show leukocytosis with a predominance of mature neutrophils and no significant left shift.

Diagnosis

The diagnosis of CNL is based on clinical, laboratory, and genetic criteria. Key diagnostic features include:

• Persistent neutrophilia (>25 x 10^9/L) with no identifiable cause of reactive neutrophilia.
• Hypercellular bone marrow with increased neutrophil precursors.
• Absence of the Philadelphia chromosome or BCR-ABL1 fusion gene, which distinguishes it from Chronic Myeloid Leukemia.
• Presence of CSF3R mutations, which are found in the majority of CNL cases.

Pathophysiology

CNL is driven by mutations in the CSF3R gene, which encodes the receptor for colony-stimulating factor 3. These mutations lead to constitutive activation of the receptor, promoting the proliferation and survival of neutrophil precursors. Other genetic abnormalities may also be present, contributing to the disease phenotype.

Treatment

The treatment of CNL is challenging due to its rarity and the lack of large clinical trials. Options include:

• Hydroxyurea, which is often used to control leukocytosis and splenomegaly.
• Interferon-alpha, which may be effective in some patients.
• JAK inhibitors, such as ruxolitinib, have shown promise in cases with JAK-STAT pathway activation.
• Allogeneic stem cell transplantation may be considered in younger patients with aggressive disease.

Prognosis

The prognosis of CNL varies, with some patients experiencing an indolent course while others progress to acute myeloid leukemia. The presence of additional genetic mutations and the response to treatment are important prognostic factors.

Also see

• Myeloproliferative Neoplasm
• Chronic Myeloid Leukemia
• Acute Myeloid Leukemia
• Neutrophilia