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Upon completion of the chapter, the reader will be able to:
Describe the pathogenesis of acute leukemia.
Identify new agents for the treatment of leukemia.
Identify the risk factors associated with a poor outcome for the acute leukemias.
Explain the importance of minimal residual disease (MRD) and its implication on early bone marrow relapse.
Explain the role of induction, consolidation, and maintenance phases for acute leukemia.
Define the role of central nervous system preventive therapy for acute leukemia.
Recognize the treatment complications associated with therapy for acute leukemias.
Describe the late effects associated with the treatment of long-term survivors of acute leukemias.
The acute leukemias are hematologic malignancies of bone marrow precursors characterized by excessive production of immature hematopoietic cells. This proliferation of “blast” cells eventually replaces normal bone marrow and leads to the failure of normal hematopoiesis and the appearance in peripheral blood as well as infiltration of other organs. These blast cells proliferate in the marrow and inhibit normal cellular elements, resulting in anemia, neutropenia, and thrombocytopenia. Leukemia also may infiltrate other organs, including the liver, spleen, bone, skin, lymph nodes, testis, and central nervous system (CNS). Virtually anywhere there is blood flow, the potential for extramedullary (outside the bone marrow) leukemia exists.
Acute leukemias are classified according to their cell of origin. Acute lymphocytic leukemia (ALL) arises from the lymphoid precursors. Acute nonlymphocytic leukemia (ANLL) or acute myelogenous leukemia (AML) arises from the myeloid or megakaryocytic precursors. As a result of clinical trials defining various prognostic (risk) factors that helped guide treatment modifications, the outcomes of acute leukemias, especially ALL, has improved dramatically over the past 50 years.1 Risk-based treatment strategies that consider multiple phenotypic and biological risk factors and attempt to match the aggressiveness of therapy with the presumed risk of relapse and death are now the standard of care. Despite the overall success in treating patients with acute leukemias, minimal advances have been made in the treatment of relapsed ALL.1
EPIDEMIOLOGY AND ETIOLOGY
Leukemia is a relatively uncommon disease. The current overall age-adjusted annual incidence of acute leukemia in the United States has remained relatively stable at 10 per 100,000 in children and 1 to 2 per 100,000 in adults.2 In 2018, it is estimated there will be 60,300 new cases of leukemia, or 3.5% of all new cancer cases.3
In the pediatric population, leukemia is a common cancer, accounting for almost one-third of all childhood malignancies. ALL accounts for 75% to 80% of all cases of childhood leukemia, whereas AML accounts for no more than 20%. Males generally are affected more often than females in all ...