The use of alternative donors, the use of peripheral blood (PB) instead of bone marrow (BM) as the stem cell source, increasing upper age limit, the use of donor lymphocyte infusions (DLIs) to treat relapse and conversion to total donor chimerism, and the use of nonmyeloablative transplants (where DLI is frequently given) have all contributed to the increase in cGVHD. cGVHD is associated with decreased quality of life, impaired functional status, and increased risk of nonrelapse mortality and morbidity (reviewed in Lee et al, Biol Blood Marrow Transplant. 2003;9:215-233). A recent randomized study found that patients receiving PB allogeneic transplants had more refractory cGVHD, requiring more courses of therapy than patients receiving BM transplants (Flowers et al, Blood. 2002;100:415-419). This finding, coupled with the randomized trial showing that the addition of cyclosporine to prednisone did not increase the response rate in newly diagnosed patients, has made finding effective therapies for cGVHD imperative (Koc et al, Blood. 2002;100:48-51).
In this issue of Blood, Seaton and colleagues report on 28 patients receiving extracorporeal photopheresis (ECP) for refractory biopsy–proven cGVHD (page 1217). Responses were scored using quantifiable variables, including extent and severity of skin involvement, liver function tests, blood counts, and pulmonary function tests. After 6 months of ECP, median skin scores were 53% lower (P = .003). The authors also studied predictive factors for response. ECP is not an easy treatment option for many patients with chronic GVHD. They must have reasonable access (financial and geographic) to a center offering ECP. ECP is given on 2 consecutive days every 2 weeks via a large catheter (often problematic for patients with sclerotic skin). The use of in-dwelling catheters, even temporary catheters, has a definite infection risk in these immunoincompetent patients. Two patients in this series appear to have had serious infections during therapy. Unfortunately, the study was unable to find pretreatment characteristics predictive for response. The study was unable to confirm a report that patients responding to ECP normalized the CD4/CD8 ratio, increased the natural killer cells, and decreased the dendritic cells (Alcindor et al, Blood. 2001;98:1622-1625; Gorgun et al, Blood. 2002;100:941-947).
The clinical results of this trial are encouraging. However, more patients need to be studied to understand the optimal way to use ECP and its immunologic effects. cGVHD needs the same intensive investigation that has been applied to acute GVHD to make real progress in this disorder.
