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