Successful Use of Extracorporeal Photochemotherapy in the Treatment of Severe Acute and Chronic Graft-Versus-Host Disease

Abstract

Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing compound 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in the treatment of several T-cell–mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. We present 21 patients (10 men and 11 women) with hematological malignancies with a median age of 36 years (range, 25 to 55 years) who had received marrow grafts from sibling (n = 12) or unrelated (n = 9) donors. Six patients had acute graft-versus-host disease (GVHD) grade II to III not responding to cyclosporine A (CSA) and prednisolone when referred to extracorporeal photochemotherapy (ECP). In 15 patients, 2 to 24 months after bone marrow transplantation (BMT), extensive chronic GVHD with involvement of skin (n = 15), liver (n = 10), oral mucosa (n = 11), ocular glands (n = 6), and thrombocytopenia (n = 3) developed and was unresponsive to conventional therapy, including steroids. All patients were treated with ECP on 2 consecutive days every 2 weeks for the first 3 months and thereafter every 4 weeks until resolution of GVHD. ECP was tolerated excellently without any significant side effects. After a median of 14 cycles of ECP, acute GVHD resolved completely in 4 of 6 patients (67%) and partially in another 2 patients. Cutaneous chronic GVHD completely resolved in 12 of 15 (80%) patients. Contractures of knees and elbows due to scleroderma resolved partially. Oral mucosal ulcerations resolved in all patients. Seven of 10 patients (70%) with liver involvement had complete responses after ECP. After discontinuation of ECP, no severe infections were observed. Our findings suggest that ECP is a safe and effective adjunct therapy for both acute and extensive chronic GVHD with skin and visceral involvement and resistance to conventional therapy. © 1998 by The American Society of Hematology.

Extracorporeal photopheresis: a useful therapy for patients with steroid-refractory acute graft-versus-host disease but not for the prevention of the chronic form

“…Two patients only had liver involvement with increased hepatic enzymes (patients 2, 3); one also had GI tract cGVHD (patient 3). cGVHD was scored as moderate in three patients (patients 2, 3, 7) and minimal in the other six (patients 1,4,5,6,8,9), who remained off immunosuppressant therapy and continued ECP as sole maintenance treatment [two consecutive days (one cycle) at 1-month intervals].…”

“…On the basis of the results obtained in our study population, ECP was confirmed to be an effective treatment in patients with steroid-refractory aGVHD grades II-III. 4,[9][10][11] Our choice of limiting the study to patients at these stages was based on evidence from the literature. In particular, Greinix et al 4 obtained encouraging results only in these grades of the disease and not in advanced stages.…”

“…4,[9][10][11] Our choice of limiting the study to patients at these stages was based on evidence from the literature. In particular, Greinix et al 4 obtained encouraging results only in these grades of the disease and not in advanced stages. The results reported by Perfetti et al, 11 who applied ECP to patients with steroidrefractory aGVHD grades II-IV, revealed that all patients at stage IV died after 1-4 years.…”

“…Depending on whether onset is early or late, 50-80% of patients with aGVHD develop cGVHD. [4][5][6] Acute and chronic overlap syndromes with features of both forms have also been described. Differences between aGVHD and cGVHD rates, time of onset, organ systems involved, types of tissue damage, clinical features and kinetics suggest that although both occur after allogeneic HSCT, the underlying immunopathological mechanisms might be different.…”

“…Extracorporeal photopheresis (ECP) has been used successfully to treat severe steroid-refractory acute and chronic GVHD since the late 1990s. 4 More recently it has also been used to prevent aGVHD in patients undergoing standard myeloablative conditioning and HSCT. 8 However, few papers have been published on patients with severe aGVHD undergoing ECP (Table 1), 4,[9][10][11] and apart from those just cited, are case reports or small uncontrolled series.…”