- Chronic myelogenous leukemia (CML) is defined by the presence of the Philadelphia chromosome (Ph), a translocation between chromosomes 9 and 22. The resulting abnormal fusion protein, p210 BCR-ABL, phosphorylates tyrosine kinase residues and is constitutively active, resulting in uncontrolled hematopoietic cell proliferation.
- The disease course of CML is characterized by a progressive increase in white blood cells over a period of years that ultimately transforms to an acute leukemia.
- The four commercially available tyrosine kinase inhibitors, imatinib, dasatinib, nilotinib, and bosutinib, have demonstrated efficacy in treatment of newly diagnosed CML patients and in patients with either accelerated phase or blast crisis.
- CML monitoring requires assessment of milestone throughout therapy such as hematologic, cytogenetic, and molecular responses, the ideal of which is a molecular response.
- Allogeneic hematopoietic stem cell transplant (HSCT) is the only known curative treatment option for CML and is reserved for patients with a suitable donor and progression after treatment with tyrosine kinase-based therapy.
- The management of CLL is highly individualized and includes observation in patients with early-stage disease and treatment with chemotherapy, biologic therapy, or both in patients with more advanced disease.
- Alemtuzumab, ofatumumab, and rituximab monoclonal antibody therapy are all indicated for the treatment of CLL. Ofatumumab is reserved for patients that have progressed following fludarabine-based and alemtuzumab-based regimens.
- Regimens such as fludarabine, cyclophosphamide, and rituximab are considered as first-line therapy for patients with CLL who are younger or have more aggressive disease, such as the presence of chromosome 17 deletion.
- Allogeneic HSCT in patients with CLL appears to achieve long-term disease-free survival in some patients, but the older patient population diagnosed with the disease and donor availability preclude widespread use.
Describe the role of the Philadelphia chromosome in the pathogenesis of chronic myeloid leukemia (CML).
Describe the epidemiology, molecular biology, clinical presentation, and disease progression of CML.
Explain the role of tyrosine kinase inhibition with regard to CML.
Choose an initial therapeutic plan in a patient with newly diagnosed CML.
Describe the currently accepted standard treatments and response monitoring parameters for CML.
Describe the role of second-generation tyrosine kinase inhibitors (TKIs) in imatinib-resistant CML and emerging evidence related to their use.
Identify options for preventing and managing toxicities, drug–drug interactions, and drug–food interactions related to TKIs.
Describe the epidemiology, molecular biology, clinical presentation, and disease progression of chronic lymphocytic leukemia (CLL).
Classify CLL based on the Rai and Binet staging system.
Explain the role of alkylator-based chemotherapy in the treatment of CLL.
Choose an initial therapeutic plan in a patient with newly diagnosed CLL.
Describe the currently accepted standard treatments and response monitoring parameters for CLL.
Describe the role of biologic therapy in the treatment of initial and relapsed CLL.
Discuss the role of hematopoietic stem cell transplant in the treatment of CML and CLL.
The chronic leukemias include chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), hairy cell leukemia, and prolymphocytic leukemia. The typical clinical presentation of the chronic leukemias is an ...