With the introduction of tyrosine kinase inhibitors (TKIs) for the treatment of patients with chronic phase myeloid leukemia (CP-CML), the survival of patients with this condition has dramatically improved in the last 10 to 15 years. Thus, the prevalence of CP-CML continues to increase while the incidence remains stable. Proper diagnosis, as well as early monitoring of responses, is crucial to secure the good outcomes seen in the randomized, controlled clinical trials.

To date, 3 different TKI therapies are approved for front-line therapy (imatinib, dasatinib, and nilotinib). However nilotinib and dasatinib have not demonstrated superiority in overall survival or progression-free survival (PFS) over imatinib, so the choice for front-line therapy for patients with CP-CML depends on several factors, including age, comorbid conditions, life expectancy, and risk stratification based on the likelihood of progression to more advance phases.

Initial Patient Presentation/History

A 55-year-old man presents to the local emergency department for an episode of left-upper-quadrant abdominal pain. A physical examination reveals an enlarged spleen 5 cm under the costal margin.

Laboratory results are as follows:

  • Complete blood cell count (CBC): Hgb 10.1 g/d
  • White blood cell count (WBC): 130 000/nL
  • Platelets: 510 000/nL
  • Peripheral blood smear:
  • WBC differential: 25% neutrophils, 23% band cells, 17% myelocytes, 10% promyelocytes, 8% basophils, 6% monocytes, 4% lymphocytes, and 8% blasts
  • Bone marrow analysis reveals a myeloproliferative disorder: 6% blasts, 8% basophils
Cytogenetic analysis is consistent with 46XY,t(9;22) in 20 out of 20 metaphases. Fluorescence in situ hybridization (FISH) is positive for BCR-ABL in all cells, and analysis by polymerase chain reaction (PCR) on the International Scale (IS) is 135%.

Previous medical history is significant for hypercholesterolemia, hypertension, and type 2 diabetes mellitus.

The patient is diagnosed with CP-CML, with high risk based on the Sokal score.

Which TKI is most appropriate for this patient?

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