Extracorporeal Photopheresis to Treat Chronic Graft-Versus-Host Disease

* INCLUSION CRITERIA: 1. Objective evidence of chronic graft versus host disease involving the skin, lungs, gastrointestinal tract, liver, or eyes. 2. Progressive or stable GvHD despite a minimum of 30 days treatment with a calcineurin inhibitor (cyclosporine or tacrolimus) at therapeutic plasma levels, plus at least one other another agent with a different mechanism of action used concurrently for at least 30 days at doses known to be therapeutic for cGvHD. In most cases this second agent will be a corticosteroid administered either as high level pulse dosing (greater than or equal to mg/kg/day prednisone or equivalent in pulses of 3 days or longer for at least two occasions during the qualifying 30 days) and/or daily dosing (greater than or equal to 0.25mg/kg) or alternate day dosing (greater than or equal to 0.50 mg/kg) prednisone or equivalent. In other cases where use of steroids is medically undesirable or contraindicated, the second agent may be mycophenolate mofetil, sirolimus, hydroxychloroquine, clofazimine, thalidomide, azathioprine, pentostatin, etanercept, Infliximab, Rituximab or Daclizumab used at doses and schedule known to provide benefit to patients with cGvHD. Patients in whom calcineurin inhibitors are medically contraindicated may also be eligible for enrollment if there has been at least a 30 day trial of prednisone (or equivalent) at the doses/schedules noted above plus one of the second agents listed above. Patients in whom both calcineurin inhibitors and steroids are medically contraindicated or in whom these agents can be used at only limiting doses may also be eligible if at least two of the alternate agents noted above have been tried for 30 days without further improvement in symptoms of cGvHD. Patients who have stabilization of disease on calcineurin inhibitors plus steroids (or the other combinations noted above), but in whom these medications cannot be tapered without disease flare are also eligible. 3. Adequate (as determined by PI) renal, hepatic, and cardiac reserve to enable the patient to tolerate Extracorporeal Photopheresis. 4. The patient's malignancy (if applicable) is in complete remission or the patient is not a candidate for further immune-based anti-tumor therapy (such as donor lymphocyte infusions or immunomodulatory cytokines) due to severity of GvHD. 5. WBC greater than or equal to 1000 and platelets greater than or equal to 25,000. 6. Weight greater than or equal to 30kg. 7. Female patients not pregnant and agree to use a reliable method of birth control during the treatment period 8. Systolic blood pressure greater than or equal to 90 mm Hg. 9. Karnofsky score or Lansky score greater than or equal to 30. 10. Predicted life expectancy of at least 3 months. 11. A minimum of 100 days following stem cell transplantation. 12. A minimum of 30 days without a response to, and 7 days following cessation of, certain investigational 2nd-line agents for treatment of GvHD (specifically: thalidomide, azathioprine, pentostatin, etanercept, Infliximab, Rituximab or Daclizumab). 13. History of failure to achieve any clinical benefit from a previous treatment with ECP where at least 3 months (12 weeks) of twice a week every other week therapy was administered. 14. Signed and witnessed informed consent. 15. Hemoglobin greater than 9.5, hematocrit greater than 28.5 (patients not meeting this inclusion criterion may be treated with iron supplementation and/or erythropoietin/darbepoetin until their hgb/hct are in the Inclusion range and may then be reconsidered for study entry). EXCLUSION CRITERIA: 1. Hypersensitivity or allergy to psoralen (methoxypsoralen). 2. Hypersensitivity to both heparin and/or citrate products. 3. Patients who are unable to visit the NIH clinical center twice a week for at least the first four week treatment period of ECP treatments; or for the NIH or arranged home treatments with ECP thereafter; or for the every 4 week medical evaluation visits to NIH. 4. Frank gastrointestinal bleeding due to GvHD (occult blood positivity excluded). 5. Patients taking a cancer chemotherapeutic agent for continued treatment of malignancy. 6. Patients undergoing radiation therapy. 7. The patient's malignancy (if applicable) is NOT in complete remission or the patient is a candidate for further immune-based anti-tumor therapy (such as donor lymphocyte infusions or immunomodulatory cytokines) to treat GvHD.