Atypical chronic myeloid leukemia

Atypical Chronic Myeloid Leukemia (aCML), also known as Chronic Myelomonocytic Leukemia 2 (CMML-2), is a rare type of leukemia that does not express the Philadelphia chromosome or BCR-ABL1 fusion gene, distinguishing it from the more common Chronic Myeloid Leukemia (CML). It is characterized by an increase in white blood cells in the blood and bone marrow, with features that are atypical of classical CML. This article provides an overview of aCML, including its symptoms, diagnosis, treatment, and prognosis.

Symptoms

Patients with aCML may present with a variety of symptoms, which can include fatigue, weight loss, fever, and night sweats. Due to the overproduction of white blood cells, individuals may also experience an enlarged spleen (splenomegaly), feeling of fullness, pain or discomfort in the left upper part of the abdomen, and easy bruising or bleeding.

Diagnosis

The diagnosis of aCML involves a combination of clinical findings and laboratory tests. Key diagnostic criteria include:

• Elevated white blood cell count with a significant number of immature white cells (myelocytes and promyelocytes)
• Absence of the Philadelphia chromosome and BCR-ABL1 fusion gene
• Presence of dysplastic features in the blood and bone marrow cells
• Exclusion of other causes of monocytosis and myelodysplastic syndromes

Bone marrow biopsy and cytogenetic analysis are critical for confirming the diagnosis and ruling out other conditions.

Treatment

Treatment options for aCML are limited and primarily focus on managing symptoms and improving quality of life. Options may include:

• Hydroxyurea to reduce white blood cell count
• Allogeneic stem cell transplantation for eligible patients, which offers the potential for a cure but comes with significant risks
• Supportive care, including blood transfusions and antibiotics for infections

Due to the rarity of aCML, patients may also be considered for clinical trials exploring new treatment options.

Prognosis

The prognosis for aCML varies and is generally considered poor, with a median survival of approximately 20-30 months from diagnosis. Factors that can influence prognosis include age, general health, and response to treatment.

Research Directions

Ongoing research is focused on understanding the genetic and molecular mechanisms underlying aCML to develop targeted therapies. The identification of specific genetic mutations in aCML patients offers hope for the development of new treatment strategies.