14 Chapter 1 CORTICOSTEROIDS Glucocorticoids, such as dexamethasone and prednisone, are important components in the treatment of ALL. Glucocorticoids regulate numerous biological processes such as metabolism, immunity, inflammation and the stress response.5 Mineralocorticoids, such as aldosterone, are another corticosteroid type, which regulate electrolyte and fluid balance.5 The naturally occurring glucocorticoid in humans is cortisol, which is produced by the adrenal cortex and which exerts a negative feedback through the hypothalamicpituitary-adrenal (HPA) axis upon endogenous production (Figure 4).5 Hydrocortisone is the medical equivalent of cortisol and is among others used as substitution therapy for patients who lack endogenous cortisol due to adrenal insufficiency.5 Prednisone and dexamethasone are synthetic glucocorticoids, a drug class that was used as the first treatment of (childhood) leukemia in the late 1940s due to the cytotoxic effect on leukemic cells.6 Prednisone, which first requires hepatic conversion to its biologically active form (prednisolone), was the preferred steroid in the treatment of ALL during many different treatment protocols. However, since the introduction of dexamethasone led to a decrease in central nervous system (CNS) relapses, and a higher event-free survival in most ALL patients, dexamethasone has been increasingly used in current treatment protocols.7-11 Figure 4. Hypothalamic-pituitary-adrenal (HPA) axis
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