Acute graft-versus-host disease (aGVHD) is partly mediated by host antigen presenting cells (APCs) that activate donor T-cells. Extracorporeal photoimmune therapy with UVADEX® (ECP) has shown benefit in some patients (pts) with GVHD, which was associated with decreased host APCs. We report preliminary results of the first multi-institutional phase II study examining ECP with a standard myeloablative preparative regimen prior to allogeneic hematopoietic stem cell transplantation (ASCT). ECP was given on two consecutive days between D-10 and D-6, followed by cyclophosphamide 60 mg/kg/day for 2 days and TBI 1200 cGy over 3 days. GVHD prophylaxis was Cyclosporine 3–5 mg/kg IV daily beginning D-1, and latter switched to PO, adjusted to keep levels 200–600 ng/ml, and methotrexate 10 mg/m2 on D1, 3, 6, and 11 for pts who had matched unrelated donors (MUD) or HLA class 1 one-antigen mismatched related donors (MMRD), or 10 mg/m2 on D1 and 5 mg/m2 on D3, 6, and 11 for pts who had matched related donors (MRD). Enrollment has been completed and data are available on 61 of 65 pts. The median age was 39 (20–60) years and 40 (66%) pts were male. Diagnoses included AML/MDS (n=20), ALL (n=14), CML (n=16), lymphoma (n=5), CLL (n=3), and other (n=3). Pts who received bone marrow (n=28) engrafted at a median of 20 (9–30) days, and pts who received peripheral blood (n=33) engrafted at a median of 15 (10–32) days. Grade II–IV and III/IV aGVHD occurred in 11 (38%) and 2 (7%) pts, respectively, who received MRD transplants (n=29), and in 16 (52%) and 10 (32%) pts, respectively, who received MUD transplants (n=31). No aGVHD occurred in 1 pt who received a MMRD transplant. Mild reversible hypotension related to ECP occurred in 1 pt who was able to continue on study. Chronic GVHD occured in 23 (42%) of 54 evaluable pts; limited in 15, extensive in 6, and unknown in 2 pts. There are 49 (80%) pts alive at a median follow up of 272 (23–560) days. Actuarial estimates of survival at one year are 93% for pts who received MRD transplants and 69% for pts who received MUD or MMRD transplants. Causes of death include relapse (n=4), aGVHD (n=3), multi-organ-system-failure (n=2), and 1 each of infection, interstitial pneumonitis, and neurologic toxicity. Preliminary results of this study reveal no adverse affects of ECP in combination with conventional preparative regimens or on engraftment after a standard myeloablative ASCT. Data correlating measurement of APCs with the incidence and severity of acute and chronic GVHD is pending. The overall survival of pts in this trial is encouraging and warrants further study.