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For instructor materials including Power Points, Answers to Clinical Encounter Questions, please contact userservices@mhprofessional.com.
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Content Update
November 17, 2019
Gilteritinib for Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia: In November 2018, the U.S. Food and Drug Administration (FDA) granted approval to gilteritinib (Xospata) for treatment of relapsed or refractory acute myeloid leukemia (AML) with an FLT3 mutation. Gilteritinib is a highly selective FLT3 inhibitor with activity against both types of FLT3 mutations. FDA approval was based on an interim analysis of response rate and duration of response in the gilteritinib arm of the ADMIRAL trial; the results of the phase 3 ADMIRAL trial were recently published. Patients randomized to receive gilteritinib had a higher complete remission rate and longer median overall survival than patients who received salvage chemotherapy. Grade 3 or higher adverse events occurred less frequently in the gilteritinib group. Based on these results, gilteritinib is now an NCCN category 1 therapy for patients with relapsed or refractory AML with FLT3 mutation.
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LEARNING OBJECTIVES
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.
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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.
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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 ...