Treatment

Chronic phase

• TKIs: first-line and second-line treatment

• Adjunctive medical treatment or hematopoietic stem cell transplantation (HSCT) may be considered if other treatments fail.

Accelerated phase

• Begin treatment with TKIs.

• Consider systemic chemotherapy or HSCT, if the patient is eligible.

Blast phase: Treatment is similar to that of acute leukemia.

• Aggressive systemic chemotherapy in combination with a TKI

• HSCT, if the patient is eligible

Indication: all patients with CML, regardless of the phase

Agents

• First-generation TKIs (imatinib): indicated in low-risk CP-CML, patients with comorbidities, or older patients

• Second-generation TKIs (e.g., dasatinib, nilotinib): usually indicated in AP-CML

• Third-generation TKIs (e.g., ponatinib): especially effective in patients with additional mutations

Mechanism of action

• Selective inhibition of tyrosine kinase (e.g., by blocking its ATP binding site): inhibits tyrosine phosphorylation of downstream signaling proteins (no phosphate transfer from ATP to tyrosine residues)

• Disruption of the BCR-ABL1 pathway: inhibits proliferation and induces apoptosis in BCR-ABL1-positive cells

Special considerations

• Second-generation and third-generation TKIs are more effective in patients with certain additional mutations than first-generation TKIs, but are also associated with more adverse events.

• TKIs can interact with many common medications and herbal supplements (e.g., antacids, antidepressants, turmeric, green tea)

• Teratogenic, therefore, they should not be used during pregnancy

Adjunctive medical treatment

• Hydroxyurea or IFN-α may be used to reduce leukocyte counts and control symptoms associated with extreme leukocytosis or thrombocytosis. [7]

Systemic chemotherapy: indicated in BP-CML and certain cases of AP-CML

Allogeneic HSCT: Should be considered in patients with TKI-resistant CML and certain patients in advanced phases (AP-CML or BP-CML)

Survival rate without treatment:

• Chronic phase: 3.5–5 years

• Blast phase: 3–6 months

In most patients, life expectancy can be markedly improved through targeted therapy with imatinib. In some cases, it even results in molecular remission.