Chronic myeloid
leukemia (CML)
- Method:
- Anticoagulant:
- Recommendation:
- Method:
- Anticoagulant:
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- Method:
- Anticoagulant:
- Recommendation:
- Method:
- Anticoagulant:
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- Method:
- Anticoagulant:
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- Method:
- Anticoagulant:
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* in (suspected) blast crisis
Through the use of tyrosine kinase inhibitors, the life expectancy of patients with chronic myeloid leukemia is almost comparable to a healthy control population. Here you can learn more about the classification, diagnosis and prognosis of CML. We also provide links for further reading on the ELTS score and the therapy of chronic myeloid leukemia.
CML: Classification
According to the WHO classification, chronic myeloid leukemia (CML) is a myeloproliferative neoplasm and is characterized by the presence of a BCR::ABL1 rearrangement. Untreated, the disease follows a biphasic or triphasic course. According to WHO 2022, the chronic phase (CP-CML) and the blast phase ("blast crisis"; BP-CML) are differentiated as the essential disease phases (WHO 2022).
CML: Diagnostic methods and their significance
CML: Prognosis
Additional chromosomal abnormalities are partly associated with a poorer prognosis
In up to 10% of patients, additional chromosomal abnormalities besides the Philadelphia translocation are observed at initial diagnosis (see above). The proportion of patients with additional alterations increases during the course of the disease and is approximately 60-80% in blast crisis (Anastasi et al. 1995, Johansson et al. 2002, Chen et al. 2017, Hehlmann et al. 2020, Hehlmann et al. 2022). Such additional chromosomal abnormalities are indicative of disease progression. In addition to point mutations in the ABL1 kinase domain, they also represent a potential cause of TKI resistance.
"High-risk" additional abnormalities are predictive for a reduced response to therapy as well as for an increased risk of progression. Accordingly, they are relevant for therapy planning (Hochhaus et al. 2020, Clark et al. 2021). High-risk additional abnormalities include the trisomies 8 and 19, isochromosome 17q, monosomy 7 or deletion(7q), 11q23 aberrations, 3q26.2 alterations, and a complex karyotype.
Quality of response is predictive for the further course
According to ELN criteria, patients should have achieved a molecular response of BCR::ABL1 ≤10% after 3 months (optimal response). If this is not the case, TKI resistance due to one or more BCR::ABL1 mutations may be underlying and may require a change of TKI depending on the mutation status (Hochhaus et al. 2020).
Achieving a major molecular response (MMR, BCR::ABL1 ≤ 0.1%) is predictive of a CML-specific survival rate approaching 100% (Hochhaus et al. 2020). In addition, it is considered established that the achievement of a deep molecular remission (BCR::ABL1 ≤0.01%) is associated with a reduced risk of loss of treatment response as well as the occurrence of TKI resistance (Branford 2020).
Clinical prognosis scores
Scores for risk assessment based on clinical parameters have been developed in each CML therapy era (Table 2).
Table 2: Comparison of different clinical scores for risk stratification in CML
Score |
Sokal (1984) |
Hasford (1998) |
EUTOS (2011) |
ELTS (2016) |
Therapy era |
Busulfan/splenectomie + intensive chemotherapie |
Interferon alpha |
Imatinib |
Imatinib |
parameters considered: |
|
|
|
|
Age |
x |
x |
|
x |
Spleen size |
x |
x |
x |
x |
Thrombocytes |
x |
x |
|
x |
Blasts in PB |
x |
x |
|
x |
Basophils in PB |
|
x |
x |
|
Eosinophils in PB |
|
x |
|
|
The EUTOS long term survival (ELTS) score described in 2016 holds the most prognostic relevance in the current era of tyrosine kinase inhibitors (Geelen et al. 2018) and should therefore be used for risk stratification according to the ELN recommendation (Hochhaus et al. 2020). The ELTS score differs from the Sokal score, which uses the same parameters for risk classification, in the weighting of the parameters (Hochhaus et al. 2020).
Prognosis calculation
This link takes you to an ELTS score online calculator for prognosis estimation.
CML: Therapy
The German guidelines for CML therapy can be found on the Onkopedia website.
Overview of clinical studies of the German CML Alliance
The linked PDF document from the University Hospital of Jena provides an overview of currently recruiting clinical studies for adult CML patients of the German CML Alliance. Currently, the information is only available in German.
CML: Recommendation
Table 3 provides an overview of which diagnostic methods are recommended by the European LeukemiaNet at which time point.
Table 3: CML diagnostics according to ELN recommendations (with modification according to Hochhaus et al. 2020)
Method |
Time point |
|||
|
At diagnosis |
Follow-up |
Therapy failure/Resistence |
(suspected) progression |
Cytomorphology |
x |
x every 2 weeks until complete hematological remission, more often in case of hematological toxicity |
- |
x determination of blast percentage
|
Immunophenotyping |
- |
- |
- |
Differentiation between myeloid and lymphoid blasts |
Chromosome analysis (Bone marrow) |
x detection of philadelphia chromosome, detection/exclusion of additional chromosomal abnormalities |
- |
x detection/exclusion of additional chromosomal abnormalities |
x detection/exclusion of additional chromosomal abnormalities |
FISH |
(x) in Ph-negative cases |
(x) for atypical BCR::ABL1 transcripts |
- |
- |
Molecular genetics |
x qualitative PCR to detect the BCR::ABL1 fusion and determination of the transcript type; optional: RQ-PCR |
x RQ-PCR every 3 months, even after reaching MMR |
x mutation analysis of the ABL1 kinase domain |
x mutation analysis of the ABL1 kinase domain |
Status: September 2023