cyclosporine A + dexamethasone + etoposide

This is a combination regimen consisting of three drugs—cyclosporine A, dexamethasone, and etoposide—used primarily in the treatment of hemophagocytic lymphohistiocytosis (HLH), particularly in pediatric and familial cases.

• Cyclosporine A is an immunosuppressant that inhibits calcineurin, thereby reducing T-cell activation and cytokine production.
• Dexamethasone is a synthetic glucocorticoid with potent anti-inflammatory and immunosuppressive effects, acting through the glucocorticoid receptor to modulate gene expression.
• Etoposide is a topoisomerase II inhibitor that induces DNA strand breaks, leading to apoptosis in rapidly dividing cells.

The HLH-2004 protocol introduced upfront cyclosporine A to intensify immunosuppression alongside the established backbone of etoposide and dexamethasone; however, studies indicate that while this combination can rescue many patients with HLH, early addition of cyclosporine does not significantly improve outcomes compared to etoposide/dexamethasone alone. This regimen aims to control hyperinflammation prior to hematopoietic stem cell transplantation.