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This chapter is dedicated in memory of James B. Nachman, MD.
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Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood and adolescence, with approximately 3500 new cases diagnosed annually in North America in patients 21 years of age and younger. ALL is defined as the presence of 25% or more malignant lymphoblasts (“blasts”) in the bone marrow. The diagnosis of ALL is often initially suspected by the presence of circulating blasts in the peripheral blood that often occurs in the setting of concomitant anemia and thrombocytopenia. Leukemia cells may also infiltrate extramedullary sites (eg, central nervous system [CNS], testes, lymphatic system, solid organs). Patients with extramedullary lymphoid masses, but less than 25% blasts in the bone marrow, are considered to have lymphoblastic lymphoma. ALL may arise from precursor B cells (B-ALL) or T cells (T-ALL).
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The incidence of childhood ALL peaks between 2 and 3 years of age (Table 445-1) and is slightly more common in males than females. The incidence of leukemia is substantially higher in white children compared to black children, with the highest rates in children of Hispanic ethnicity. With the exception of Down syndrome and rare familial leukemia predisposition syndromes, causal factors of childhood ALL remain largely unknown. Epidemiologic studies have also investigated various environmental factors (eg, viral infections, parental smoking, living near power lines) potentially associated with increased risk of childhood ALL, although definitive associations have not been proven. Exposure to very high doses of ionizing radiation, chemicals such as benzene, and certain chemotherapies have been associated with an increased risk of acute myeloid leukemia (AML), but not ALL.
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Remarkable progress has been made in the treatment of children with ALL during the past 6 decades. This success is largely attributable to improved understanding of key biologic and genetic features of childhood ALL that has informed risk stratification of patients, as well as to appropriate therapeutic intensification for children with high-risk disease. Enhanced supportive care has also decreased morbidity and mortality and contributed to improved outcomes. In the 1960s, fewer than 10% of children with ALL were cured. In 2016, more than 90% of all children with newly diagnosed ALL can be cured with modern frontline therapy (Fig. 445-1). Relapse-free survival exceeds 95% for a subset of patients with the most favorable genetic features and treatment response. Patients are generally considered cured if they remain in remission more than ...