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

  1. Explain the role of the Philadelphia chromosome in the pathophysiology of chronic myelogenous leukemia (CML).

  2. Describe the natural history of CML.

  3. Identify the clinical signs and symptoms associated with CML.

  4. Discuss treatment options for CML with special emphasis on tyrosine kinase inhibitors.

  5. Describe the clinical course of chronic lymphocytic leukemia (CLL).

  6. Describe patients who may be observed without treatment and those who receive aggressive treatment for CLL.

  7. Discuss the various treatment options available for CLL.

  8. Describe the clinical presentation of multiple myeloma.

  9. Discuss the treatment options available for multiple myeloma.




  • Image not available. The Philadelphia chromosome (Ph) is a chromosomal translocation responsible for chronic myelogenous leukemia (CML).

  • Image not available. The Ph results in the formation of an abnormal fusion gene, BCR-ABL, which encodes an overly active tyrosine kinase.

  • Image not available. Allogeneic stem cell transplantation is the only curative treatment option for CML.

  • Image not available. Nearly all patients with CML are treated initially with a tyrosine kinase inhibitor (TKIs).

  • Image not available. Dasatinib and nilotinib are two second-generation TKIs that can overcome imatinib resistance or intolerance.

  • Image not available. Chronic lymphocytic leukemia (CLL) can have a variable disease course, but most patients survive for many years.

  • Image not available. Chemotherapy does not improve overall survival in early stage CLL.

  • Image not available. Fludarabine-based chemotherapy is commonly used as first-line therapy for younger patients with CLL.

  • Image not available. Autologous transplant either as a single or double transplant offers younger patients with myeloma longer disease-free survival.

  • Image not available. Newer therapies for multiple myeloma, including thalidomide, lenalidomide, and bortezomib in combination with dexamethasone, produce major responses.




Several diseases comprise chronic leukemia. The two most common forms are chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia (CLL). The slower progression of the disease contrasts it from acute leukemia, with the survival of chronic leukemia often lasting several years without treatment. This chapter covers CML and CLL. The chapter also discusses multiple myeloma and provides a brief discussion of Waldenström macroglobulinemia.




CML is a hematologic cancer that results from an abnormal proliferation of an early myeloid progenitor cell. The clinical course of CML has three phases: chronic phase, accelerated phase, and blast crisis.1 Chemotherapy can be used to control white blood cell (WBC) counts in the chronic phase, but as CML slowly progresses, the cancer becomes resistant to treatment. Blast crisis resembles acute leukemia, and immediate aggressive treatment is required. Table 96–1 describes each of the phases of CML.

Table Graphic Jump Location
Table 96–1Clinical Course of CML

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