Julie A Ross

Leukemias (all types) account for less than 3 percent of the worldwide cancer burden.1 In the United States, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) comprise approximately 1 percent of all newly diagnosed malignancies and 1.5 percent of all cancer deaths each year.2 Although ALL can be diagnosed at any age, it is typically more common in childhood. In contrast, the incidence of AML is higher in adults, increasing notably with age.3 Five-year survival rates for childhood ALL have increased dramatically over the past 50 years, rising from about 5 percent in the 1960s to nearly 75 percent in the 1990s.2,4-7 Although children diagnosed with AML do not fare as well, their 5-year survival rates have increased from about 2 percent to about 40 percent during this same time period. In contrast, adults diagnosed with either ALL or AML have generally poor survival rates. For example, adults diagnosed with either ALL or AML between 45 and 54 years of age experience 5-year survival rates of about 1 percent and 19 percent, respectively.3

Major advances in molecular biology and immunology have increased our understanding of the malignant processes that occur during hematopoietic cell transformation. With the exception of a few established associations, however, little is known about the causes of acute leukemia. This paucity of knowledge may partly be attributable to small studies that lack statistical power to adequately explore differences and inadequate characterization of leukemia type. These factors can also make it difficult to make direct comparisons between studies. For example, historically, epidemiological studies did not uniformly address differences between acute and chronic forms of leukemia or between lymphoid and myeloid lineages. Even with the introduction of more recent classifications schemes, such as the French-American-British (FAB) system, it is becoming increasingly apparent that even these distinctions may be inadequate. Further subgroups (such as children with hyperdiploidy ALL and adults with promyelocytic leukemia) are being defined by their responses to therapy. Hence, it is possible that these subgroups may also be defined by different etiologies. Although there are some similarities among risk factors associated with childhood and adult leukemia, there are enough differences overall in both molecular characteristics (e.g., cytogenetics) and prognostic factors to suggest that the cause(s) may not be the same. This chapter reviews the current knowledge regarding the etiology of childhood and adult acute leukemia.

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