A single-center pilot validation study of a new chronic GVHD skin scoring system.

The use of a quantifiable and reproducible measurement tool for skin manifestations of chronic graft-versus-host disease (cGVHD) is key for the successful assessment and documentation of therapeutic response. Skin scoring methods for use in clinical trials have not been validated for application in patients suffering from cGVHD. For this purpose we performed a prospective single-center pilot study to validate a skin-scoring tool developed at our institution for evaluating cutaneous involvement of cGVHD approximately 10 years ago. It combines percentage of involved body surface area (BSA) divided into 10 separate anatomic regions with manifestations of cGVHD coded from 0 (normal skin) to 4 (hidebound skin, unmovable sclerosis). Sixteen patients were examined separately by 4 trained physicians 3 times on 2 consecutive days for a total of 192 individual skin assessments; intraobserver and interobserver reliability were calculated. Good to excellent intraclass correlation coefficients (ICC) were obtained in almost all scores including erythematous lesions in areas with scores 3 and 4 for all observers. Moderate to good interrater reliability for observers 1 to 4 was seen in lesions with scores 0, 3, and 4, respectively. A marked improvement of interrater reliability in all scores and examinations was observed when ICCs were calculated only for the more experienced observers 1 to 3. This New Chronic GVHD Skin score is a reproducible, accurate, feasible, and inexpensive tool for use in selected clinical trials of chronic cutaneous GVHD. Further studies with larger patient numbers and validation of this new tool for assessment of treatment response are warranted.

A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis.

BACKGROUND: Systemic sclerosis is a multisystemic connective tissue disease with marked involvement of the skin and joints for which few effective evidence based therapies are available. To further investigate the efficacy of extracorporeal photochemotherapy on early aggressive cutaneous disease, a randomized, double-blind, placebo-controlled trial was performed. OBJECTIVE: Our aim was to evaluate the efficacy of photopheresis in the treatment of patients with systemic sclerosis (scleroderma). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted at 16 investigational sites in the United States, Canada, and Europe. Sixty-four patients with typical clinical and histologic findings of scleroderma, of less than 2 years' duration, were studied. Patients did not receive any other concomitant treatment for scleroderma. Patients were randomized to receive either active or sham photopheresis treatment on two consecutive days monthly for 12 months. Severity of skin (skin scores assessed in 22 body regions) and joint involvement (60 joints examined for contractures) were assessed on a monthly basis. RESULTS: A statistically significant improvement in skin scores as compared with baseline was observed at 6 months (P = .0024) and 12 months (P = .008) among those who received active photopheresis, but not among those who received sham photopheresis. Comparison of skin scores between the two study arms did not achieve statistical significance because of the small sample size of the study arms. Joint involvement was also significantly improved after 6 months (P = .002) and 12 months (P = .001) of active photopheresis when compared with baseline. LIMITATIONS: The study lacks sufficient statistical power to reveal a significant difference in skin and joint manifestations between the active and sham photopheresis arms. CONCLUSION: Photopheresis induced significant improvement of skin and joint involvement in patients with scleroderma of recent onset; however, any effect when compared with sham treatment and a possible placebo effect may be modest.

The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease.

Acute graft-versus-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation. We performed a phase II study on patients with acute steroid-refractory GVHD grades II to IV given extracorporeal photochemotherapy (ECP) weekly and analyzed response and long-term survival. Complete resolution of GVHD was achieved in 82% of patients with cutaneous involvement, 61% with liver involvement, and 61% with gut involvement. The probability of survival was 59% among patients who responded completely to ECP compared to 11% in patients not responding completely. We conclude that intensified ECP is highly effective in acute GVHD and that sustained responses are associated with over 50% long-term survival.

Sézary syndrome and seronegative polyarthritis: treatment with extracorporeal photochemotherapy.

We describe a patient with therapy-resistant cutaneous T-cell lymphoma, Sézary syndrome variant, in association with concurrent polyarthritis and vitiligo, who was successfully treated with extracorporeal photochemotherapy (ECP). The combination of Sézary syndrome with seronegative rheumatoid arthritis is rare. In our patient the T-cell lymphoma was refractory to standard treatments that included psoralen-UVA, lymph node irradiation, and polychemotherapy. ECP has been shown to be effective in the treatment of selected cases of Sézary syndrome. There is a strong suggestion that ECP as a monotherapy can provide a significant benefit for other T-cell-mediated diseases including rheumatoid arthritis. In spite of a disease duration of 10 years, a very low CD8 cell count (2% of lymphocytes), a very high CD4 cell count (94%), and multiple unsuccessful chemotherapeutic trials before initiation of ECP, our patient achieved a long-lasting complete remission of both diseases with normalization of the CD4+ and CD8+ T-lymphocyte subsets. Concurrent developing vitiligo was unaffected by ECP.

Effects of extracorporeal photoimmunotherapy on soluble IL-2Ralpha, TNF-RI, and CD8 in patients with steroid-resistant acute graft-versus-host disease.

Extracorporeal photoimmunotherapy (ECP) has been successfully used as adjunct treatment for steroid-resistant graft-versus-host disease (GvHD) after allogeneic stem cell transplantation. We serially investigated serum levels of soluble interleukin-2 receptor-alpha (sIL-2Ralpha), soluble tumor necrosis factor receptor I (sTNF-RI), and soluble CD8 (sCD8) in 19 patients with steroid-resistant acute GvHD before and after each ECP treatment. Highest levels of sIL-2Ralpha and sTNF-RI correlated with severe acute GvHD and infections. Despite an immediate sIL-2Ralpha and sTNF-RI decrease after each treatment cycle, a mean surge of sTNF-RI>sIL-2Ralpha during the first three ECP cycles was observed in infections. A delayed surge, i.e., after the third ECP cycle, of sIL-2Ralpha and elevated post-ECP sCD8 levels was observed in patients developing chronic GvHD. While levels of sIL-2Ralpha and sTNF-RI correlate with the severity of acute GvHD and infections during the early ECP treatment period, the recurring increase of post-ECP sCD8 possibly may serve as parameter for developing chronic GvHD.