sirolimus + tacrolimus + methotrexate

This combination regimen, developed and evaluated by Yale University, is a prophylactic strategy designed to prevent acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation, particularly those receiving grafts from mismatched unrelated donors. The regimen integrates three immunosuppressive agents with distinct and complementary mechanisms of action: sirolimus (an mTOR inhibitor), tacrolimus (a calcineurin inhibitor), and a short course of low-dose methotrexate (an antimetabolite). By simultaneously targeting multiple pathways of T-cell activation and proliferation, the protocol aims to reduce the incidence and severity of aGVHD while maintaining the beneficial graft-versus-tumor effect. A Yale-led pilot study and subsequent long-term follow-up have demonstrated the safety and efficacy of this triple-drug approach in high-risk transplant populations.

Other names

Sirolimus, Tacrolimus and Short Course MethotrexateYale GVHD prophylaxis regimenSirolimus-Tacrolimus-Methotrexate Regimen