Extracorporeal Photopheresis in Steroid-Refractory Acute or Chronic Graft-versus-Host Disease: Results of a Systematic Review of Prospective Studies

Abstract

Acute and chronic graft-versus-host disease (GVHD) remain major obstacles for successful allogeneic hematopoietic cell transplantation. Extracorporeal photopheresis (ECP) modulates immune cells, such as alloreactive T cells and dendritic cells, and improves GVHD target organ function(s) in steroid-refractory GVHD patients. We performed a systematic review to evaluate the totality of evidence regarding the efficacy of ECP for treatment of acute and chronic steroid-refractory or steroid-dependent GVHD. Nine studies, including 1 randomized controlled trial, met inclusion criteria, with a total of 323 subjects. In pooled analyses, overall response rates (ORR) were .69 (95% confidence interval [CI], .34 to .95) and .64 (95% CI, .47 to .79) for acute and chronic GVHD, respectively. In acute GVHD organ-specific responses, ECP resulted in the highest ORR for cutaneous, with .84 (95% CI, .75 to .92), followed by gastrointestinal with .65 (95% CI, .52 to .78). Similar response rates were seen in chronic GVHD involving the skin and gastrointestinal tract. Conversely, ORR for chronic GVHD involving the lungs was only .15 (95% CI, 0 to .5). In chronic GVHD, grades 3 to 4 adverse events were reported at .38 (95% CI, .06 to .78). ECP-related mortality rates were extremely low. Rates of immunosuppression discontinuation were .55 (95% CI, .40 to .70) and .23 (95% CI, .07 to .44) for acute and chronic GVHD, respectively. In summary, albeit limited by numbers of available studies, pooled analyses of prospective studies demonstrate encouraging responses after ECP treatment in acute and chronic GVHD after failing corticosteroids. Further research efforts are needed to improve organ-specific responses.

An update on the clinical utility of extracorporeal photopheresis in the treatment of graft-versus-host disease

“…Expected response rates vary by organ system involved, with skin GVHD having the highest overall response rate (ORR) of 60-80%. In a systematic review by Abu-Dalle et al, 44 ORR for aGVHD was 0.69 with organ-specific response being the highest in cutaneous aGVHD (0.84 ORR) followed by GI GVHD (0.65 ORR). Patients with higher grade aGVHD may benefit from aggressive, up-front ECP with three treatments per week for the first 4 weeks.…”

“…ORRs and organ-specific efficacy were similar between both studies (with GI and lung cGVHD showing less response to ECP treatment). In the study by Abu-Dalle et al, 44 ORR for cGVHD was 0.64. Response rates for cGVHD involving the skin and GI tract were 0.71 and 0.62, respectively; in contrast, the ORR for cGVHD involving the lungs was only 0.15.…”

Extracorporeal Photopheresis: Scientific and Technical Considerations for Improving Clinical Management of Patients

“…Indeed, ECP seems to be safe in these immunodepressed populations with low rates of grade 3-4 events and particularly the absence of infectious complications [37]. For other indications such as aGVHD, peripheral T lymphomas with circulating clones, some immune disorders, there is a potent benefit that should be considered with other available treatments.…”

“…Two recent synthetic analyses sought to more precisely define the efficacy of ECP in aGVHD. A meta-analysis based on nine relevant prospective studies showed a pooled overall response rate of 0.69 (skin 0.84, gut 0.65, liver 0.65) [37]. A Recent review reports similar results in response with an impact of ECP response on overall survival in multivariate analysis that is much more meaningful for clinical practice [39].…”

“…In GVHD patients, ECP is almost always associated at least with a corticosteroid treatment, so the reduction of immunosuppressive-associated therapies seems to be a more reliable global assessment. Despite these difficulties, ECP demonstrates significant results in cutaneous, gastrointestinal, hepatic, oral, ocular or musculoskeletal cGVHD (recent meta-analysis by AbuDalle, et al) in both, pediatric or adult patients [37]. The decrease of corticosteroids has also been reported as significant and consistent criteria for ECP response.…”