Chronic Myelomonocytic Leukemia

• CMML is a rare blood cancer characterized by an overproduction of monocytes and abnormal myeloid cells in the bone marrow and blood.
• Symptoms are often non-specific and can include fatigue, unintended weight loss, fever, and an enlarged spleen.
• The exact causes of CMML are largely unknown, but it is associated with acquired genetic mutations in blood-forming stem cells.
• Treatment strategies vary based on disease risk and patient health, ranging from watchful waiting to chemotherapy or allogeneic stem cell transplantation.

What is Chronic Myelomonocytic Leukemia (CMML)?

Chronic Myelomonocytic Leukemia (CMML) is a rare cancer that affects the blood-forming cells in the bone marrow. It is unique among blood cancers because it has characteristics of both myelodysplastic syndromes (MDS), where blood cells are abnormal and don’t mature properly, and myeloproliferative neoplasms (MPN), where there is an overproduction of certain types of blood cells. Specifically, CMML is defined by a persistent increase in monocytes in the blood (monocytosis) and often an increase in other myeloid cells, along with signs of dysplasia (abnormal development) in at least one myeloid cell line in the bone marrow.

This condition primarily affects older adults, with a median age of diagnosis typically around 70 years. According to the American Cancer Society, CMML is relatively uncommon, accounting for approximately 3% of all myelodysplastic syndromes and having an incidence of about 1 in 100,000 people per year. The disease can progress over time, and in some cases, it may transform into acute myeloid leukemia (AML).

Chronic Myelomonocytic Leukemia Symptoms and Causes

The presentation of chronic myelomonocytic leukemia symptoms can be quite varied, and many individuals experience non-specific signs that can be mistaken for other conditions. These symptoms arise from the abnormal production of blood cells, leading to issues like anemia, low platelet counts, or an overabundance of white blood cells. Common symptoms include:

• Persistent fatigue and weakness
• Unexplained weight loss
• Fever and night sweats
• Easy bruising or bleeding due to low platelet counts
• Frequent infections due to dysfunctional white blood cells
• An enlarged spleen (splenomegaly), which can cause abdominal discomfort or a feeling of fullness
• Skin rashes or lesions

Regarding the causes of chronic myelomonocytic leukemia, the exact mechanisms are not fully understood. It is generally considered an acquired genetic disorder, meaning the mutations occur during a person’s lifetime rather than being inherited. Researchers have identified several recurrent genetic mutations in myeloid stem cells that are frequently associated with CMML. These include mutations in genes such as TET2, SRSF2, ASXL1, and CBL. These genetic changes disrupt the normal regulation of blood cell production and maturation, leading to the characteristic features of CMML. However, having these mutations does not guarantee the development of CMML, and many individuals with CMML do not have a clear identifiable risk factor.

Chronic Myelomonocytic Leukemia Treatment

The approach to chronic myelomonocytic leukemia treatment is highly individualized, depending on the patient’s specific symptoms, overall health, and the risk stratification of their disease. Risk stratification typically considers factors like bone marrow blast percentage, cytogenetic abnormalities, and specific gene mutations. The primary goals of treatment are to manage symptoms, improve blood counts, prevent disease progression, and enhance quality of life.

Treatment options may include:

For low-risk, asymptomatic patients, a “watch and wait” approach may be adopted, involving regular monitoring without immediate intervention. For those with more advanced disease or significant symptoms, therapeutic options include:

Hypomethylating agents, such as azacitidine or decitabine, are often used to modify gene expression in cancer cells, aiming to reduce the number of abnormal cells and improve blood counts. These agents can help control the disease and may delay progression to acute myeloid leukemia. Hydroxyurea may be prescribed to reduce high white blood cell counts and manage symptoms related to an enlarged spleen. In certain cases, targeted therapies may be considered if specific genetic mutations are identified that can be addressed by available drugs. For eligible patients, allogeneic stem cell transplantation (a transplant using stem cells from a donor) is currently the only potentially curative treatment option for CMML, though it carries significant risks and is typically reserved for younger, fitter patients with higher-risk disease.