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).
Identify the clinical signs and symptoms and laboratory findings associated with CML, chronic lymphocytic leukemia (CLL), and multiple myeloma (MM).
Discuss first- and second-line treatment options for CML, including options for those patients with drug-resistant disease.
Describe the clinical course of CLL and distinguish which patients may be observed and who require treatment.
Compare the treatment options available for CLL, noting treatment differences based on the drug’s toxicity profile.
Describe the clinical presentation and symptoms of MM.
Recommend the appropriate treatment for patients with MM, recognizing the importance of combination therapy and the role of autologous hematopoietic stem-cell transplant.
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. There have been numerous treatment advancements in the area of targeted therapy for each of these cancers, resulting in an increase in survival.
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 (CP-CML), accelerated phase (AP-CML), and blast phase/crisis (BP-CML), with 90% of patients diagnosed in chronic phase.1 Criteria for these phases is largely based on the percent blasts in the peripheral blood or bone marrow. Blast crisis resembles acute leukemia, and immediate aggressive treatment is required.
EPIDEMIOLOGY AND ETIOLOGY
There were an estimated 9110 new cases of CML diagnosed in 2021, accounting for 14% of all adult leukemias.2 The incidence of CML increases with age, with the median age of diagnosis being 65 years.3 Prior to the advent of imatinib, the annual mortality was 10% to 20%. Today, with the use of tyrosine kinase inhibitors (TKIs), the annual mortality has decreased to 1% to 2%.1 In most newly diagnosed cases, the etiology cannot be determined. High doses of ionizing radiation and exposure to solvents such as benzene are recognized as 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, megakaryoid, and (rarely) lymphoid lineages. These cells remain functional in CP-CML, which is why patients in chronic phase are at low risk for developing infections.
The Philadelphia chromosome (Ph) results from a translocation between chromosomes ...