Agestratified Therapy

A series of systematic clinical trials in children with ALL has resulted in such high cure rates for the majority of patients (EFS of more than 75% for most patients) that current risk-adapted clinical trials in the pediatric cooperative groups are beginning to explore less intensive therapy for very good risk patients, with the goal of achieving similar results with fewer long-term side effects. In contrast, as discussed in detail above, the outcome for ALL in adults is considerably less favorable, with overall cure rates of less than 30%. Factors contributing to this marked difference include significant differences in the molecular genetics of adult ALL, with a higher incidence (30% in adults and 5% in children) of the unfavorable (9;22) Philadelphia chromosome translocation in adults and a virtual absence of the favorable TEL-AML1 fusion gene resulting from a cryptic translocation, the t(12;21).113-115 In addition, other negative risk factors include comorbid medical conditions in the aging population and poorer tolerance of chemotherapy, particularly of intensive treatment with L-asparaginase and higher dose MTX, drugs that have been used with great success in the pediatric population.116

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