Chronic myelomonocytic leukemia

CMML

Chronic Myelomonocytic Leukemia (CMML) is a rare type of cancer that primarily affects the blood and bone marrow. It is characterized by the increased production of monocytes, a type of white blood cell, in the bone marrow. CMML is a type of leukemia that shares characteristics of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), making it a unique and complex disease to understand and treat.

Etiology and Pathogenesis

The exact cause of CMML is not well understood, but it is believed to involve genetic mutations in the hematopoietic stem cells. These mutations lead to the abnormal growth and accumulation of monocytes and other cells in the bone marrow and blood. Several genetic mutations have been associated with CMML, including mutations in the TET2, ASXL1, and SRSF2 genes. However, the presence of these mutations alone is not sufficient to cause the disease, suggesting that additional factors are involved in its development.

Classification

CMML is classified into two subtypes based on the white blood cell count in the peripheral blood:

• CMML-1: White blood cell count is less than 13,000/μL
• CMML-2: White blood cell count is 13,000/μL or more, and/or the presence of more immature blood cells (blasts) in the blood or bone marrow.

This classification is important for determining the prognosis and guiding treatment decisions.

Symptoms

Symptoms of CMML can vary widely among patients and may include fatigue, fever, weight loss, and easy bruising or bleeding. Some patients may experience an enlarged spleen (splenomegaly) or liver (hepatomegaly), which can cause discomfort or pain in the left upper abdomen. Infections are common due to the abnormal function of the white blood cells.

Diagnosis

The diagnosis of CMML involves a combination of clinical examination, blood tests, and bone marrow analysis. Blood tests typically show an increased number of monocytes and may also reveal anemia, thrombocytopenia (low platelet count), or leukocytosis (high white blood cell count). A bone marrow biopsy is essential for confirming the diagnosis, allowing for the examination of the bone marrow cells under a microscope and the identification of any genetic mutations associated with CMML.

Treatment

Treatment for CMML is tailored to the individual patient and may include supportive care, drug therapy, and in some cases, stem cell transplantation. Supportive care focuses on relieving symptoms and may include blood transfusions, antibiotics to treat infections, and medications to control fever and pain. Drug therapy for CMML may involve the use of hydroxyurea to reduce the white blood cell count or hypomethylating agents such as azacitidine or decitabine, which can help control the disease in some patients. Allogeneic stem cell transplantation is the only potential cure for CMML but is associated with significant risks and is typically considered only for younger patients in good overall health.

Prognosis

The prognosis for patients with CMML varies depending on several factors, including the subtype of CMML, the patient's age, and overall health. CMML-2 is associated with a poorer prognosis than CMML-1 due to the higher risk of transformation to acute myeloid leukemia (AML). The median survival for patients with CMML ranges from 12 to 24 months, but individual outcomes can vary widely.

Conclusion

Chronic Myelomonocytic Leukemia is a complex and challenging disease that requires a comprehensive approach to diagnosis and treatment. Ongoing research into the genetic and molecular mechanisms underlying CMML is essential for developing more effective therapies and improving outcomes for patients.