The development of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of chronic myeloid leukemia (CML).1,2 However, despite effectively inducing remission and prolonging survival in patients with CML, TKI therapy does not eradicate leukemia stem cells (LSCs), which are responsible for drug resistance, relapse, and disease progression.2 Given recent changes to the treatment paradigm, updated clinical practice guidelines are essential to ensure optimal clinical care is provided.2

The British Society for Haematology (BSH) published a guideline update for the investigation and management of CML in adults and children in the British Journal of Haematology.1 Lead author of the guidelines, Graeme Smith, MD, of St James’s University Hospital in the United Kingdom, and coauthors, developed the evidence-based recommendations to provide clinical practitioners with clear guidance on the diagnosis and treatment of adults and children with CML (Tables 1 and 2).

Diagnosis and Key Investigations

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The diagnosis of CML is established based on findings from a peripheral blood smear and bone marrow aspirate showing positivity for BCR-ABL1, and the presence of the Philadelphia (Ph) chromosome. The Ph chromosome, or a variant, is present in approximately 95% of CML cases. Other cases include a cryptic BCR-ABL1 fusion, commonly detected by reverse transcriptase polymerase chain reaction (RT-PCR), or fluorescence in situ hybridization (FISH). Additional findings from bone marrow aspirate include the presence of other cytogenetic abnormalities, including isochromosome 17q or trisomy 19, and trisomy 8, suggesting a higher risk of progression to accelerated phase or blast crisis in adults.

Table 1. Selected Recommendations by the BSH Guideline Panel on the Diagnosis of CML1

RecommendationGRADE Criteria
At diagnosis, a bone marrow aspirate should be performed for full karyotype analysis and to confirm the phase of the diseaseGrade 2B
Establishing the fusion type is required for molecular monitoring to guide future managementGrade 1B
It is useful to calculate the ELTS* score to inform prognosis  Grade 2B
Abbreviations: BSH, British Society for Haematology; CML, chronic myeloid leukemia; ELTS, EUTOS long-term survival; GRADE, Grading of Recommendations Assessment. * The only prognostic score of value in children.

Table 2. ELTS Score Calculation1

Risk GroupELTS Score*
Low-risk group≤1.5680
Intermediate-risk group>1.5680 – ≤2.2185
High-risk group>2.2185
Abbreviation: ELTS, EUTOS long-term survival
*ELTS score = 0.0025 x (age/10)3 + (0.0615 x spleen size below costal margin) + (0.1052 x blasts in peripheral blood) + [0.4104 x (platelet count x 109 per l/1000) – 0.5]