Skip to Main Content

LEARNING OBJECTIVES

LEARNING OBJECTIVES

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. Identify the clinical signs and symptoms and laboratory findings associated with CML, chronic lymphocytic leukemia (CLL), and multiple myeloma (MM).

  3. Discuss first- and second-line treatment options for CML, including options for those patients with drug-resistant disease.

  4. Describe the clinical course of CLL and distinguish which patients may be observed and who require treatment.

  5. Outline the treatment options available for CLL, noting treatment differences based on variations in the tumor’s molecular profile.

  6. Describe the clinical presentation and symptoms of MM.

  7. Recommend the appropriate treatment for patients with MM, recognizing the importance of combination therapy and the role of autologous hematopoietic stem cell transplant.

INTRODUCTION

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 MM.

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 crisis (BP-CML), with 90% of patients diagnosed in chronic phase.1 Criteria for these phases are 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

There were an estimated 8430 new cases of CML diagnosed in 2018, 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 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.

PATHOPHYSIOLOGY

Cell of Origin

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 CP-CML, which is why patients in this phase are at low risk for developing infections.

Ph Chromosome

Image not available. 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 ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.