THE USE OF GLUCOCORTICOIDS IN ACUTE LYMPHOBLASTIC-LEUKEMIA OF CHILDHOOD - MOLECULAR, CELLULAR, AND CLINICAL CONSIDERATIONS

Glucocorticoids have been included in almost all treatment regimens fo r childhood acute lymphoblastic leukemia for decades. However, optimal agents, doses, and/or schedules have yet to be defined despite extens ive clinical application. New data on the pharmacokinetics, pharmacody namics, and molecular mechanisms of action of glucocorticoids have sug gested alternative approaches in ALL. These suggest that prolonged, i. e. 28 day, glucocorticoid therapy may be unnecessary as exposure to gl ucocorticoid induces down-regulation of glucocorticoid receptors. Dexa methasone may be superior to prednisone in conventional equi-effective doses. Blast sensitivity to glucocorticoids correlates closely with s ensitivity to other, putatively non-cross-resisting agents and with ou tcome after multi-agent therapy, suggesting overlapping mechanisms of action, and focusing attention on the determinants of the threshold fo r apoptosis. Increasing success in the treatment of childhood acute ly mphoblastic leukemia has led to increasing awareness of avascular necr osis of bone as a potentially disabling sequela of glucocorticoid ther apy, especially in adolescent and young adult patients.