Sirolimus is an oral mammalian target of rapamycin (mTOR) inhibitor that is approved by the US Food and Drug Administration (FDA) for rejection prophylaxis in renal transplant patients.1 Sirolimus works through mTOR to produce a blockade of B- and T-cell activation and antibody product.1

Additionally, sirolimus may have antineoplastic effects2 and inhibit smooth muscle proliferation.  As health care practitioners gained more experience with sirolimus, it began to be used “off-label” to prevent rejection in multiple transplant recipients outside of the kidney including liver, heart, and lung. Based on its success in the solid organ transplant world, sirolimus has also been evaluated in prevention and treatment of graft versus host disease (GVHD).

GVHD is an unfortunate complication of allogeneic hematopoietic stem cell transplant (HSCT). The pathophysiology underlying GVHD is complex, however it typically occurs when the donor cells (graft) attack the host’s cells after they are identified as foreign.3

This is clinically manifested in numerous systems within the body including the skin, gastrointestinal tract, liver, kidneys, and lung.  There are some discrepancies on how to define acute GVHD compared with chronic GVHD within the literature, however a common cutoff point is 100 days post-HSCT, with acute GVHD occurring before 100 days and chronic GVHD occurring thereafter.4

There are numerous treatment options for acute and chronic GVHD including topical and systemic steroids and mycophenolate mofetil. Sirolimus is one such medication that can be considered an off-label second line treatment option (as well as for prophylaxis) when a patient’s symptoms are refractory to steroids. Unfortunately, many of the studies formally evaluating sirolimus in GVHD are relatively small which should be kept in mind when considering its use, especially in dosing and monitoring.