From the Guidelines
CML transformation refers to the progression of chronic myeloid leukemia from the chronic phase to either accelerated phase or blast crisis, which represents a more aggressive disease state, and is characterized by the acquisition of additional genetic abnormalities beyond the Philadelphia chromosome, leading to increased proliferation and decreased differentiation of myeloid cells 1.
Key Points
- The transformation of CML is driven by the BCR-ABL1 fusion gene, which codes for a protein with high tyrosine kinase activity, and is associated with the development of additional genetic abnormalities, such as point mutations of the kinase domain or additional cytogenetic aberrations 1.
- The European LeukemiaNet (ELN) definition of CML phases is recommended as a basis for treatment decisions, and includes the chronic phase, accelerated phase, and blast crisis 1.
- The recommended approach for managing CML transformation includes immediate initiation of tyrosine kinase inhibitors (TKIs) and consideration of allogeneic stem cell transplantation, as it offers the best chance for long-term survival 1.
Treatment Approach
- TKIs, such as imatinib, dasatinib, or nilotinib, should be initiated immediately to target the BCR-ABL1 fusion gene 1.
- Chemotherapy regimens, such as hyperCVAD, may be considered for blast crisis 1.
- Allogeneic stem cell transplantation should be pursued as soon as possible after achieving remission, as it offers the best chance for long-term survival 1.
Monitoring and Follow-up
- Regular monitoring of BCR-ABL transcript levels is essential to assess treatment response 1.
- Bone marrow biopsy and cytogenetic testing should be performed to confirm transformation and guide therapy 1.
From the FDA Drug Label
By 7 years, transformation to either accelerated or blast phase occurred in nine patients on treatment in the 100 mg once-daily treatment group
- Transformation of Chronic Myeloid Leukemia (CML): transformation to either accelerated phase or blast phase.
- The exact mechanisms or pathways of transformation are not specified in the provided text.
- Key finding: 9 patients transformed to either accelerated or blast phase after 7 years on treatment with dasatinib 100 mg once daily 2
From the Research
Transformation of Chronic Myeloid Leukemia (CML)
- CML is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, which is defined by the BCR::ABL1 oncogene that develops after fusion of the ABL1 proto-oncogene to the constitutively active BCR gene 3.
- The disease progresses through different phases, including:
- Chronic phase: defined as blasts of less than 10% in the blood or bone marrow, absence of extramedullary evidence of leukemia, basophils of less than 20%, and platelet counts of 100 to 1000 × 10^9/L 3.
- Accelerated phase: characterized by an increase in blasts, basophils, or platelets, and a decrease in platelet counts 4, 5, 6.
- Blastic phase: the most advanced stage, characterized by 20% or more blasts/immature cells in the blood or bone marrow 3.
- The transformation of CML is driven by the BCR::ABL1 fusion oncogene, which leads to the proliferation of leukemic cells and the development of the disease 4, 5, 6.
- The progression of CML can be influenced by various factors, including the patient's age, disease stage, and response to treatment 3, 4, 5, 6.
- Treatment options for CML include tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, bosutinib, and nilotinib, which target the BCR::ABL1 oncogene and can help to control the disease 3, 4, 5, 6, 7.
- Allogeneic hematopoietic stem cell transplantation is also a treatment option for patients with CML, particularly those who have failed multiple TKIs or have advanced-phase disease 3, 4, 5, 6.