The one-two punch of dexamethasone (DEX) and RUX in treating CSS. Cytokines interleukin-2 (IL-2), IL-7, and IL-15 signal through lymphocyte cell surface cytokine receptors activating JAK proteins which leads to phosphorylation (P) of STAT5. Phosphorylated STAT5 homodimers enter the nucleus and transcriptionally activate prosurvival genes such as BCL-2. DEX triggers apoptosis via engagement of the glucocorticoid receptor (GR) and its nuclear signaling, and RUX inhibits JAK/STAT signaling to provide a one-two punch with DEX to overcome cytokine-induced survival signals that allow for lymphocyte cell death via apoptosis.