ruxolitinib + tacrolimus + methotrexate

**ruxolitinib + tacrolimus + methotrexate** is a combination regimen under clinical investigation for the prevention of graft-versus-host disease (GVHD) in pediatric and adult patients undergoing allogeneic hematopoietic stem cell transplantation, particularly for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS)[1][3][4][5][6][7][9]. - **Ruxolitinib** is a small molecule JAK1/2 inhibitor that antagonizes signaling through Janus kinases, suppressing pro-inflammatory pathways and reducing T-cell activation and tissue damage[1][4][9][10]. - **Tacrolimus** is a calcineurin inhibitor that suppresses T-cell activation by inhibiting IL-2 transcription, commonly used to prevent organ and bone marrow transplant rejection[4][6][7][9]. - **Methotrexate** is an antimetabolite and antifolate chemotherapy agent that prevents DNA synthesis and cell division, and also acts as an immunosuppressant to reduce risk of GVHD[1][4][9]. This combination is being studied to determine if synergistic immunosuppression and anti-inflammatory effects are more effective than current standard regimens for GVHD prophylaxis in the setting of stem cell transplantation. All three drugs are FDA-approved individually, but use in this precise combination for GVHD prevention is investigational[1][2][7][9].