From the Guidelines
Chronic Myelomonocytic Leukemia (CMML) type 2 is a specific subtype of CMML, characterized by a higher percentage of blast cells in the blood and bone marrow, with 5-19% blasts in the blood or 10-19% blasts in the bone marrow, indicating a more aggressive disease with a poorer prognosis compared to CMML-1. This classification is based on the WHO classification system, which distinguishes CMML-1 and CMML-2 based on the percentage of blasts plus monocytes in peripheral blood and bone marrow 1. The symptoms of CMML-2 include fatigue, weakness, easy bruising, frequent infections, and enlarged spleen.
Key Characteristics of CMML-2
- Higher percentage of blast cells in the blood and bone marrow compared to CMML-1
- 5-19% blasts in the blood or 10-19% blasts in the bone marrow
- More aggressive disease with a poorer prognosis compared to CMML-1
- Symptoms include fatigue, weakness, easy bruising, frequent infections, and enlarged spleen
Treatment Options for CMML-2
- Supportive care (blood transfusions, antibiotics)
- Hypomethylating agents like azacitidine or decitabine
- Chemotherapy
- Allogeneic stem cell transplantation for eligible patients
Genetic Mutations in CMML-2
- TET2, ASXL1, and SRSF2 are commonly found genetic mutations in CMML-2
- These mutations contribute to the disease's development and progression by disrupting normal blood cell production and maturation
Management of CMML-2
- Regular monitoring of blood counts and bone marrow examinations are essential for managing this condition and evaluating response to treatment 2
- Comprehensive diagnostic criteria, including persistent peripheral blood monocytosis, no Philadelphia chromosome or BCR-ABL1 fusion gene, and less than 20% blasts in the peripheral blood and bone marrow, are necessary for accurate diagnosis 2
From the Research
Definition and Classification of Chronic Myelomonocytic Leukemia (CMML)
- CMML is a myelodysplastic syndrome/myeloproliferative overlap neoplasm characterized by sustained peripheral blood monocytosis and an inherent risk for transformation to acute myeloid leukemia (15-30% over 3-5 years) 3.
- CMML is morphologically classified into CMML-0,1, and 2 based on peripheral blood and bone marrow promonocyte/blast counts 3.
- A more clinically relevant classification into dysplastic and proliferative subtypes, based on the presenting white blood cell count, is helpful in prognostication and therapeutics 3.
CMML Type 2
- CMML-2 is characterized by a higher percentage of blasts and promonocytes in the bone marrow and peripheral blood compared to CMML-0 and CMML-1 3.
- The diagnosis of CMML-2 is based on the presence of 5-19% blasts (including promonocytes) in the bone marrow or 4-19% blasts (including promonocytes) in the peripheral blood 4.
- Patients with CMML-2 have a higher risk of transformation to acute myeloid leukemia and a poorer prognosis compared to those with CMML-0 and CMML-1 5, 6.
Risk Stratification and Management
- Risk stratification models, such as the Mayo Molecular Model (MMM), can help identify high-risk patients who may benefit from allogeneic stem cell transplant (ASCT) 5, 6.
- Hypomethylating agents, such as 5-azacitidine and decitabine, are commonly used to treat CMML, but have limited efficacy and do not alter the natural course of the disease 3, 5, 6.
- ASCT is the only potentially curative option for CMML, but is associated with significant morbidity and mortality 3, 5, 6.