Description
Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder driven by the BCR-ABL fusion gene, which produces an abnormal tyrosine kinase. The introduction of tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib has revolutionized CML treatment, transforming it into a manageable chronic condition. Effective management requires regular molecular monitoring using quantitative PCR to assess BCR-ABL transcript levels and guide therapy adjustments. Resistance mutations, adherence issues, and side effects must be carefully addressed. Ongoing research into newer TKIs and treatment-free remission strategies continues to improve long-term outcomes and quality of life for patients with CML.
Summary Listen
- Chronic Myeloid Leukemia (CML) arises from myeloid progenitor cells due to a genetic translocation between chromosomes 9 and 22, forming the Philadelphia chromosome and the BCR-ABL1 oncogene. This leads to excessive cell proliferation and reduced apoptosis. While the incidence in Western data is 1.5-2 per lack, in India it's 0.8-2.2 per lack. CML is more common in males and the median age of diagnosis in India (35-40 years) is lower than in the West (55-65 years).
- Targeted therapy using tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment, significantly improving survival rates. TKIs inhibit the BCR-ABL1 protein, preventing uncontrolled cell growth. Treatment selection considers factors like age, comorbidities, cost, and risk profile, with the aim of achieving hematological normalization, complete cytogenetic response (CCyR), and major molecular response (MMR) to minimize relapse risk.
- Risk assessment in CML involves scoring systems like the Sokal and ELTS scores, which help predict outcomes and guide treatment decisions. Patients are classified into low, intermediate, and high-risk groups. While imatinib remains effective, second-generation TKIs may be preferred for higher-risk patients, aiming for deeper molecular responses.
- Monitoring CML treatment involves assessing hematological, cytogenetic, and molecular responses. Hematological response is monitored through CBC, cytogenetic response via bone marrow examination, and molecular response through quantitative PCR. Key time points for monitoring include 3, 6, and 12 months, with specific BCR-ABL1 transcript levels used to determine response and guide further treatment.
- Treatment resistance in CML requires a strategic approach, involving second-line and third-line TKIs. The choice of subsequent therapy depends on the initial treatment and the specific resistance patterns. In cases of TKI failure, allogeneic hematopoietic stem cell transplant (allo-HSCT) may be considered.
Sample Certificate
About the Speakers
Dr. Ram Ganjoo
Senior Consultant Medicine & Clinical Haematology, Sarvodaya Medicentre, Delhi
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