A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease

Abstract Chronic graft-versus-host disease (cGVHD) is a major limitation of successful hematopoietic cell transplantation. The safety and efficacy of extracorporeal photopheresis (ECP) for 12 to 24 weeks together with standard therapy was compared with standard therapy alone in patients with cutaneous manifestations of cGVHD that could not be adequately controlled by corticosteroid treatment. The primary efficacy end point was a blinded quantitative comparison of percent change from baseline in Total Skin Score (TSS) of 10 body regions at week 12. Ninety-five patients were randomized to either ECP and standard therapy (n = 48) or standard therapy alone (n = 47). The median percentage improvement in TSS at week 12 was 14.5% for the ECP arm and 8.5% for the control arm (P = .48). The proportion of patients who had at least a 50% reduction in steroid dose and at least a 25% decrease from baseline in TSS was 8.3% in the ECP arm at week 12 and 0% in the control arm (P = .04). The nonblinded investigator assessment of skin complete or partial responses revealed a significant improvement in favor of ECP (P < .001). ECP was generally well tolerated. These results suggest that ECP may have a steroid-sparing effect in the treatment of cGVHD. Clinical trials registered at www.ClinicalTrials.gov as NCT00054613

A Multi-Institutional Study of Extracorporeal Photoimmune Therapy with UVADEX® for the Prevention of Acute GVHD in Patients Undergoing Standard Myeloablative Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract 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.</jats:p