The etiology of childhood leukemia is unknown and is probably multifactorial. Genetics and environmental factors play important roles. There are many recurrent nonrandom chromosomal translocations in leukemia cells. A translocation may lead to the formation of a new gene, whose expression may lead to a novel protein with transforming capabilities. In chronic myelogenous leukemia (CML) and some cases of acute lymphoblastic leukemia (ALL), a translocation between chromosomes 9 and 22 results in a fusion gene incorporating parts of two genes, BCR and ABL. The protein formed by this novel gene plays an important role in the development of the leukemias. In addition, certain constitutional genotypes can predispose a child to the development of acute leukemia. Patients with Down syndrome, Fanconi anemia, Bloom syndrome, ataxia-telangiectasia, Wiskott-Aldrich syndrome, and neurofibromatosis 1 all have an increased risk of acute leukemia. Siblings of children with leukemia are at increased risk of developing leukemia (approximately twofold to fourfold above the childhood population). This risk increases for twin siblings (up to 25% for monozygotic twins). In certain patients with leukemia, the unique antigen receptor gene rearrangement or the specific chromosomal translocation characterizing the patient’s leukemic clone can be demonstrated in cord blood cells and neonatal blood spots used for screening for metabolic diseases, suggesting a possible in utero etiology. There are reports of familial leukemia. Environmental factors that may increase the risk of leukemia include ionizing radiation and exposure to certain chemotherapy agents, particularly the topoisomerase II inhibitors.
Each year 2500 to 3500 new cases of childhood leukemia occur in the United States. The disease affects about 40 per 1 million children under the age of 15 years. ALL accounts for approximately 75% of cases. Acute myelogenous leukemia (AML)accounts for 15% to 20%, and CML accounts for less than 5% of cases. Other chronic leukemias, including juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, and chronic lymphocytic leukemia, are rare in childhood.
ALL and AML are classified according to the World Health Organization system (Table 155-1), although many clinicians and pathologists still use the French-American-British system for AML. ALL is classified according to cell lineage as either B-lineage or T-lineage. The incidence of ALL peaks at 2 to 5 years of age and is higher in boys than in girls. T-cell ALL, in particular, is associated with male predominance as well as an older age of peak incidence. In the United States, ALL is more common in white than in African American children.The incidence of AML is relatively high in the neonatal period then drops and stabilizes until adolescence when there is a slight increase, which continues into adulthood, especially beyond 55 years of age. Males and females are equally affected by AML. Hispanic and African American children have slightly higher incidence rates than white children.
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