Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection

Abstract

Purpose of review: Glucocorticoids are a mainstay in acute lymphoblastic leukemia treatment and lack of early response is predictive for overall disease prognosis. Given the vital position of glucocorticoids and well known long and short-term side effects associated with differing glucocorticoids, we aim to highlight the wide breadth of historical and more contemporary data to describe the current landscape of glucocorticoid use in this arena.

Recent findings: Emerging studies aim to overcome issues such as steroid resistance and to optimize the antileukemic effects of glucocorticoids while aiming to mitigate the risks and side effects associated with their exposure. Glucocorticoids have and likely always will be a fundamental component of acute lymphoblastic leukemia treatment and understanding how to navigate short- and long-term effects and how to optimize regimens is at the heart of continued treatment success.

Keywords: Acute Lymphoblastic Leukemia; Glucocorticoid; Regimen; Resistance.

Fig. 1

Agents Used in Glucocorticoid Resistance. Signaling pathways including downstream JAK/STAT, PI3K/AKT/mTOR, and MAPK-ERK have been identified in glucocorticoid resistance and have been shown to be induced by activation of the the IL-7 signaling pathway. Agents capable of blocking signaling pathways involved in the ALL glucocorticoid resistance including Idelalisib, Pictilisib and Buparlisib (PI3 kinase inhibition), ruxolitinib (JAK 1/2 inhibition), and Selumetinib, Trametinib and Binimetinib (MAPK inhibition) have been explored