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  • Image not available. 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.
  • Image not available. 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.
  • Image not available.Imatinib is a tyrosine kinase inhibitor and is the most commonly used therapy in the treatment of chronic phase CML. Second-generation tyrosine kinase inhibitors, dasatinib and nilotinib, are active in most patients that have resistance or intolerance to imatinib.
  • Image not available.Interferon alfa (IFN-α) plays a minor role in the current treatment of CML and is reserved for patients who fail tyrosine kinase inhibitors and are ineligible for allogeneic hematopoietic stem cell transplant (HSCT).
  • Image not available. Allogeneic 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.
  • Image not available. 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.
  • Image not available.Alemtuzumab is a monoclonal antibody against CD52, which is expressed on B and T cells. It has proven activity in first-line treatment and relapsed disease. Routine use must be balanced against the known risks of opportunistic infections.
  • Image not available. 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.
  • Image not available. 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.

On completion of the chapter, the reader will be able to:

  • 1. Explain the molecular pathogenesis of chronic myeloid leukemia (CML).
  • 2. Describe the natural history of CML.
  • 3. Define hematologic response, cytogenetic response, and molecular response in CML.
  • 4. Describe the mechanism of action of imatinib in the treatment of CML.
  • 5. Describe imatinib dosing in chronic phase, accelerated phase, and blast crisis CML.
  • 6. Assess the extent and rate of achieving disease response in patients on imatinib compared to interferon alfa.
  • 7. Describe the side effects seen with imatinib and interferon alfa–based therapy.
  • 8. Discuss the role of dasatinib in the treatment of CML.
  • 9. Compare and contrast the role of allogeneic stem cell transplant and imatinib using concepts of patient age, donor availability, and time from diagnosis.
  • 10. Discuss the natural history of chronic lymphocytic leukemia (CLL).
  • 11. Describe the biologic markers that can help predict prognosis in CLL.
  • 12. Compare and contrast CLL patients who should receive conservative therapy and those who should receive aggressive therapy.
  • 13. Describe watchful waiting, chlorambucil, or fludarabine-based therapy as initial management of CLL.
  • 14. Describe the use of alemtuzumab in ...

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