From the Guidelines
Chronic Myeloid Leukemia (CML) progresses through three distinct phases: chronic, accelerated, and blast phases, as defined by the presence of the Philadelphia chromosome and the BCR-ABL1 fusion gene 1.
Phases of CML
The phases of CML are characterized by the following features:
- Chronic phase: less than 10% blast cells in blood or bone marrow, often asymptomatic or experiencing mild symptoms like fatigue or splenomegaly, and typically responds well to tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, or dasatinib 1.
- Accelerated phase: disease progression with 10-19% blasts, increasing basophils (>20%), persistent thrombocytopenia, and chromosomal abnormalities beyond the Philadelphia chromosome, requiring higher TKI doses or alternative agents 1.
- Blast phase: the most severe stage, resembling acute leukemia with over 20% blasts, extramedullary disease, and poor prognosis, managed with intensive chemotherapy regimens combined with TKIs, and allogeneic stem cell transplantation considered for eligible patients 1.
Management and Monitoring
Regular monitoring of BCR-ABL transcript levels is essential for tracking treatment response and detecting early progression between phases 1. The choice of therapies for individual patients is determined by considerations of efficacy, tolerability, early and late toxicity, and drug costs, with a focus on quality of life and avoiding long-term organ toxicities 1.
Treatment
First-line treatment is a tyrosine kinase inhibitor (TKI), with generic imatinib being the cost-effective initial treatment in chronic phase CML, and various contraindications and side-effects of all TKIs should be considered 1. Allogeneic transplantation continues to be a therapeutic option, particularly for advanced phase CML, and treatment discontinuation may be considered in patients with durable deep molecular response (DMR) with the goal of achieving treatment-free remission (TFR) 1.
From the Research
Phases of Chronic Myeloid Leukemia (CML)
- The phases of CML include:
- CML is usually diagnosed in the chronic phase in developed countries 3
- The primary goal of tyrosine kinase inhibitor (TKI) therapy in patients with chronic phase-CML is to prevent disease progression to accelerated phase-CML or blast phase-CML 3
- Patients diagnosed in AP are at higher risk of failure as compared to CP patients, but if they achieve optimal responses with frontline TKI treatment their outcome may be similarly favorable 2
- Patients diagnosed in BP may be treated with TKI alone or with TKI together with conventional chemotherapy regimens, and subsequent transplant decisions should rely on kinetics of response and individual transplant risk 2
- Patients in CP progressing under TKI treatment represent the most challenging population and they should be treated with alternative TKI according to the mutational profile, optional chemotherapy in BP patients, and transplant should be considered in suitable cases after return to second CP 2