What is the treatment approach of CML?
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
Describe the targeted therapy with tyrosine kinase inhibitors in CML.
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
What are further treatment options in CML?
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)
Describe the treatment of CLL.
Indications for anticancer therapy: based on disease risk (Rai staging) and disease activity
Low-risk disease (Rai stage 0)
Expectant management
Intermediate risk disease (Rai stage I or II)
Consider expectant management if stable and asymptomatic.
Medical therapy: indicated for progressive or symptomatic disease (i.e., active disease)
High-risk disease (Rai stage III or IV): medical therapy
Anticancer therapy may include:
Targeted therapy, e.g., ibrutinib, rituximab, alemtuzumab
Chemoimmunotherapy, e.g., FCR: fludarabine, cyclophosphamide, rituximab
Allogeneic HSCT: currently the only curative treatment option (not routinely performed)
Describe the treatment approach of acute leukemia.
The treatment of acute leukemia is decided by a hematologist-oncologist specialist depending on the specific subtype and results of molecular testing.
Pretreatment: All patients should have prechemotherapy screening as part of preparation for cancer treatment.
Chemotherapy
Systemic chemotherapy: The regimen of choice is based on individual patient and disease factors.
Intrathecal chemotherapy (commonly used): Consider adding for patients with or at high risk of CNS infiltration (e.g., all patients with ALL).
Targeted chemotherapy: Consider adding for leukemias with specific immunophenotype and genetic profiles, e.g., Philadelphia translocation.
Adjunctive treatment, e.g., radiation therapy, immunotherapy, or stem cell transplantation (SCT): Consider based on individual evaluation.
Supportive care: Provide holistic care to reduce symptoms and support patients and carers (see “Principles of cancer care”).
Management of complications: initiate monitoring, prevention, and early aggressive treatment as needed for infection, bleeding, pancytopenia, and oncologic emergencies (see “Management of complications”).
List commonly used agents for ALL.
Alkylating agents: e.g., cyclophosphamide
Anthracyclines: e.g., daunorubicin, doxorubicin
Antimetabolites: e.g., cytarabine, methotrexate, 6-mercaptopurine
Enzyme therapy: e.g., L-asparaginase
Alkaloids: e.g., vincristine
Glucocorticoids: e.g., prednisone, dexamethasone
List commonly used agents for AML.
Anthracyclines (e.g., idarubicin, high-dose daunorubicin)
Antimetabolites (e.g., cytarabine, methotrexate)
Hypomethylating agents (e.g., azacitidine)
List the agents for APL.
Differentiation agents: to induce the maturation of immature malignant WBCs
ATRA (All-trans retinoic acid)
Arsenic trioxide
Chemotherapy with anthracyclines (e.g., idarubicin)
In APL, the t(15;17) translocation and subsequent formation of the PML-RARA fusion gene can inhibit myeloblast differentiation under physiological levels of retinoic acid. High doses of ATRA (a vitamin A derivative) may induce myeloblast differentiation and promote remission.
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