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Acute myeloid leukemia (AML) accounts for approximately 20% of cases of acute leukemia in children versus 80% of cases of acute leukemia among adults. Over the past 20 years, there has been little improvement in rates of cure for AML despite maximally intensive therapy; with intensive therapy, 50% to 60% of children with AML will survive. This is in contrast to childhood acute lymphoblastic leukemia (ALL), where more than 85% of children will survive. In fact, survival rates in ALL continue to increase even with deintensification of treatment to reduce long-term side effects, and with improvement in quality of life in clearly defined subsets of children with ALL. AML therapy remains maximally toxic and requires multiple, near myeloablative courses of treatment with chemotherapeutic agents and often hematopoietic stem cell transplantation (HSCT). Recent progress in AML has largely been through the identification of genomically defined risk groups. Genetic events predictive of higher and lower cure rates permit the allocation of patients to conventional cytotoxic therapy or HSCT, respectively, while other genetic events provide promise for more targeted therapies.
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The chronic myeloid forms of leukemia are extremely rare in children. These myeloproliferative syndromes (MPS) most commonly include the adult type of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML), and juvenile myelomonocytic leukemia (JMML). The clinical course, biologic characteristics, and molecular pathogenesis of CML and JMML are quite different. Until recently, allogeneic HSCT from either a related or an unrelated donor was the management of choice for children with Ph+ CML but the kinase inhibitor imatinib has changed the treatment paradigm for that disease in both children and adults, although HSCT is still the only known curative therapy for CML. Similarly, allogeneic HSCT remains the only known curative option for children with JMML.
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The annual incidence of AML throughout childhood remains constant, except for slight peaks during infancy and adolescence. In fact, in infants, AML is more common than ALL. There are approximately 7 cases per million children per year, or approximately 600 new cases per year in the United States. After age 20 years, the incidence of AML slowly increases with age (Fig. 446-1). There is a slightly higher incidence in Hispanic children with 9 cases per million per year. The incidence also appears slightly higher in Japan, Australia, and Zimbabwe.
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The cause of AML is unknown, and most children have no known predisposing factors. Known risk factors include exposure to high-dose ionizing radiation, previous chemotherapy (especially with alkylating agents and epipodophyllotoxins), Down syndrome, congenital bone marrow failure syndromes (Diamond-Blackfan anemia and Kostmann agranulocytosis; see Chapter 437), chromosome fragility and impaired DNA repair mechanisms (such as Fanconi anemia), and inherited disorders, such as neurofibromatosis type 1 (NF1). Neurofibromatosis type 1 ...