Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

Inclusion Criteria: * Age ≥ 13 years * Weight ≥ 40 kg. * Biopsy or clinical presentation diagnostic of chronic GVHD \>100 days following allogeneic bone marrow/peripheral blood/umbilical cord blood transplantation that has failed prior corticosteroid therapy or corticosteroid taper. In the event that histological confirmation poses undue risk, clinical evaluation is sufficient. * Women of child-bearing potential must have a negative pregnancy test before sirolimus administration and agree to use a medically acceptable contraceptive throughout the treatment period until 3 months after discontinuation of sirolimus. * Any woman becoming pregnant during the treatment period must discontinue the use of sirolimus. * Absolute neutrophil count (ANC) \> 1000/mm³, unless receiving G-CSF to maintain neutrophil count \> 500/mm³. * At the time of initiating sirolimus the cyclosporine trough level is recommended to be \< 100 mg/dl and FK506 level is recommended to be \< 5 mg/dl. FK506 or cyclosporine is to be discontinued soon after initiation of sirolimus. * Karnofsky performance score ≥ 50 during pre-study screening. * Written, signed, and dated informed consent Exclusion Criteria: * Uncontrolled systemic infection * Unstable disease states (i.e., hepatic failure, ventilatory-dependent respiratory failure, etc.) * Serum creatinine ≥ 3.0 mg/dL * Platelet count ≤ 50,000/mm³ * History of Post-transplant microangiopathic hemolytic anemia * Uncontrolled hyperlipidemia * Use of any investigational drug within 4 weeks of entry into the study * Use of methotrexate or antibody therapies within 24 hours of sirolimus administration * Inability to tolerate oral therapy for any reason * Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening * Known hypersensitivity to macrolide antibiotics