Sirolimus for GVHD prophylaxis in allogeneic stem cell transplantation.

Sirolimus is a novel macrolide immunosuppressant widely used in solid organ transplantation. We have conducted three clinical trials using this compound as prophylaxis against GVHD after allogeneic stem cell transplantation. Our studies have demonstrated excellent GVHD control even when mismatched and unrelated donors were used. The morbidity and mortality associated with transplantation were reduced due to the omission or reduction in methotrexate dose. Furthermore, CMV reactivation and fungal infection rates were low. However, we have noted that sirolimus may be associated with increased rates of thrombotic microangiopathy after transplantation. Sirolimus has other uses, such as the treatment of established acute and chronic GVHD, and may be useful for treatment of post transplant lymphoproliferative disorder and perhaps as an antineoplastic agent against a wide variety of hematologic and solid neoplasms.