Upon completion of the chapter, the reader will be able to:
Explain the role of the Philadelphia chromosome in the pathophysiology of chronic myelogenous leukemia (CML).
Describe the natural history of CML.
Identify the clinical signs and symptoms and laboratory findings associated with CML.
Discuss treatment options for CML with special emphasis on tyrosine kinase inhibitors.
Describe the clinical course of chronic lymphocytic leukemia (CLL).
Describe patients who may be observed without treatment and those who receive aggressive treatment for CLL.
Discuss the various treatment options available for CLL.
Describe the clinical presentation of multiple myeloma.
Discuss the treatment options available for multiple myeloma.
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 the hematologic cancer multiple myeloma.
CHRONIC MYELOGENOUS LEUKEMIA
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 Criteria for these phases is largely based on the percent blasts in the peripheral blood or bone marrow. 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.
EPIDEMIOLOGY AND ETIOLOGY
It was estimated that 6660 new cases of CML would be diagnosed in 2015, accounting for 15% of all adult leukemias.2 The incidence of CML increases with age, the median age being 67 years.3,4 In most newly diagnosed cases, the etiology cannot be determined, but high doses of ionizing radiation and exposure to solvents such as benzene are recognized risk factors.
CML arises from a defect in an early progenitor cell. The pluripotent (noncommitted) stem cell is implicated as the origin of the disease; therefore, multiple cell lineages of hematopoiesis may be affected, including myeloid, erythroid, megakaryocyte, and (rarely) lymphoid lineages. These cells remain functional in chronic phase CML, which is why patients in this phase are at low risk for developing infections.
KEY CONCEPT The Philadelphia chromosome (Ph) results from a translocation between chromosomes 9 and 22, leaving a shortened chromosome 22. The Ph results in the formation of an abnormal fusion gene between the breakpoint cluster region and the Abelson proto-oncogene (BCR-ABL), which encodes an overly active tyrosine kinase. The loss of control of tyrosine kinase activity causes abnormal cellular proliferation ...