Why is age such an important independent prognostic factor in acute lymphoblastic leukemia?

Despite the use of similar intensive chemotherapy regimens, adults with acute lymphoblastic leukemia (ALL) exhibit a strikingly inferior outcome when compared to children. Mirroring this difference in prognosis, childhood and adult ALL exhibit distinctive age-related differences in potential etiologic factors and underlying biology. Childhood ALL mostly occurs in industrialized countries, with a unique peak in incidence between the ages of 2 and 8 years. It is associated with features conferring a favorable response to therapy, including early pre-B cell disease and a hyperdiploid karyotype or a cryptic t(12;21) translocation. The lymphoblasts of childhood ALL appear to arise in a developmental compartment that is "poised" for apoptotic death and are particularly sensitive to glucocorticoids, antimetabolites, and other cytotoxic agents. In contrast, adult ALL commonly possesses the poor-prognosis Philadelphia chromosome and is often drug-resistant. A far higher proportion of adults with ALL present with high initial white blood cell count and high-risk immunophenotypes, and exhibit a slow induction of remission with greater therapy-related toxicity. Improved supportive care measures with current intensive therapies and the development of novel leukemia-targeted biotherapies will be required to improve the cure rates of adults with ALL.