Acute Leukemias in Adults
Summary of Key Points
Incidence
• There were 13,780 new cases of acute myeloid leukemia (AML) and 6,050 new cases of acute lymphocytic leukemia (ALL) in the United States in 2012, resulting in 10,200 deaths from AML and 1440 from ALL. The incidence of AML is relatively low until age 35 and then rises almost exponentially, whereas ALL peaks in incidence in young children. Risk factors for the development of acute leukemia include exposure to benzene, ionizing radiation, or previous chemotherapy.
Biological Characteristics
• The acute leukemias are clonal disorders, with all leukemic cells in a given patients descending from a common precursor. Recent genomewide analyses of leukemia have demonstrated considerable complexity with a number of recurrent potential “driver” mutations and a much larger number of random “passenger” mutations in individual cases.
Diagnosis and Classification
• The diagnosis of acute leukemia is generally made by bone marrow examination. In the past, the classification of acute leukemia depended heavily on morphologic examination of the leukemic cells. This is no longer the case, and currently the most important elements of classification are the immunophenotype (to distinguish AML from ALL), cytogenetics, and mutational analyses. In AML, three primary-risk groups are recognized. Favorable-risk patients are those with CBF translocations, and those with normal cytogenetics and either NMP1 or CEBPA mutations without mutations in FLT3-ITD. Unfavorable-risk patients are those with abnormalities of 3q, 5 or 7, and those with complex cytogenetics. The intermediate-risk group includes all those not classified as favorable or unfavorable. Acute promyelocytic leukemia, characterized by t(15;17), is a separate entity and requires specific therapy. In ALL, the favorable-risk group includes those with high hyperdiploidy, and del9q. The unfavorable-risk group includes t(4;11), low hypodiploidy/near triploidy, and those with complex cytogenetics. All others comprise the intermediate-risk group. Patients with t(9;22) (Ph+ ALL) and mature B-cell ALL including Burkitt leukemia comprise separate categories of ALL that require specific treatment.
Treatment
Patients With AML Who Are Candidates for Intensive Therapy
• Induction chemotherapy that includes an anthracycline plus cytarabine will result in a complete remission in approximately 70% of patients. Postremission therapy depends on the risk group. Favorable-risk patients are generally treated with three or four cycles of consolidation chemotherapy, including high-dose cytarabine. With such treatment, approximately 50% of patients will be cured. Patients with intermediate-risk disease should undergo allogeneic transplantation while in first remission if they have a matched sibling or matched unrelated donor. The use of partially matched donors in this setting is less agreed on. Allogeneic transplantation using matched siblings, matched unrelated donors, or partially matched cord blood is recommended for patients with unfavorable-risk disease in first remission.
