Photopheresis treatment

Treatment of acute graft-versus-host disease with photopheresis

Successful treatment of acute graft-versus-host disease (aGVHD) with extracorporeal photopheresis (ECP) has been reported in several studies.^8,37,38 Greinix et al. reported a complete response rate to photopheresis of 100% grade II, 67% grade III, and 12% grade IV aGVHD, and there was a complete resolution of GVHD in 60% of cases with skin, and 67% with liver aGVHD.³⁷

More recently Greinix et al. reported on 59 aGVHD patients treated with photopheresis. Complete resolution of aGVHD was achieved in 82% of patients with cutaneous involvement, 61% with liver involvement, and 61% with gut involvement.³⁸ The Kaplan-Meier estimates for overall survival at 4 years were 47% for all patients, 59% for patients achieving a complete resolution of aGVHD and 11% for those who did not achieve complete resolution in response to ECP (p = <0.0001).

A 2006 review published in the British Journal of Dermatology reported an overall response rate of aGVHD to photopheresis of 58% in skin and 40% in liver.⁸

Photopheresis treatment regimens for acute graft-versus-host disease

In the initial Greinix et al. study aGVHD patients were treated with ECP on 2 consecutive days at 1 – 2 week intervals until improvement, after which they were treated every 2 to 4 weeks with photopheresis until maximal response.³⁷ Based on this experience and due to the stability of ECP responses, Greinix et al. amended the treatment protocol in the second study so that ECP was given on 2 consecutive days at weekly intervals and was stopped immediately after achieving maximal response.

Treatment of chronic graft-versus-host disease with photopheresis

There have been more studies on the treatment of chronic graft-versus-host disease (cGVHD) with photopheresis than the treatment of aGVHD, and a recent evidence based review in the British Journal of Dermatology found that there was a Strength of Recommendation level B and a Quality of Evidence level II-ii for the use of ECP to treat cGVHD with cutaneous or mucosal involvement³⁶

Chronic GVHD studies include a prospective trial of 25 patients treated with ECP in which 20 patients had improvement in cutaneous GVHD and 80% benefited from a steroid sparing effect; and a retrospective analysis of 32 cGVHD patients treated with photopheresis that produced a complete response (CR) rate of 22% and the partial response (PR) rate of 34%.^18,40 The steroid-sparing response rate in the Apisarnthanarax et al. study was 64%.⁴⁰

Couriel et al reported on 71 patients with cGVHD who were treated with ECP.¹⁹ The overall response rate was 61%, with 20% of patients showing CR, and highest responses were achieved in cGVHD of the skin (59%), liver (71%), oral mucosa (77%), and eye (67%). There was a substantial response (54%) in patients with bronchiolitis obliterans (6 patients, 54%).

In the first prospective randomised controlled clinical trial of ECP for the treatment of cGVHD, Flowers et al. compared ECP plus conventional therapy with conventional therapy alone in 95 patients. Although the primary endpoint did not achieve significance (14.5% ECP treated patients improved their Total Skin Score [TSS] compared to 8.5% of the conventional therapy group at 12 weeks; p = 0.48); the study did report a significant effect for steroid sparing. In the ECP treated group, a significant number of cGVHD patients treated with photopheresis experienced at least a 50% reduction in steroid dose and a 25% or greater decrease in TSS from baseline in the first 12 weeks of treatment (8.3% ECP vs. 0% control; p = 0.04). Furthermore, a significant number of cGVHD patients treated with ECP experienced a ≥ 50% reduction in steroid dose and a lowering of steroid dose to less than 10 mg/day in the first 12 weeks of treatment (20.8% ECP vs. 6.4% control; p = 0.04).

Photopheresis treatment regimens for chronic graft-versus-host disease

Photopheresis treatment regimens for cGVHD vary between studies. In the Foss et al. study ECP was administered for 2 consecutive days every 2 weeks in 17 patients and once a week in 8 patients until best response or stable disease.¹⁸ In the Apisarnthanarax et al. study patients were treated with photopheresis once or twice a week, and in the Couriel et al. study ECP was administered 2 to 3 times a week and tapered according to clinical response at the discretion of the managing physician.^19,40 In the Flowers study, patients were treated with ECP 3 times in the first 7 days, then twice weekly for 12 weeks, tapered to two treatments every 4 weeks for another 12 weeks.¹⁶