A Prospective Trial of Extracorporeal Photopheresis for Chronic Graft-versus-Host Disease Reveals Significant Disease Response and No Association with Frequency of Regulatory T Cells

Abstract

Extracorporeal photopheresis (ECP) is an accepted treatment for chronic graft-versus-host disease (cGVHD); however, the mechanism of action is unclear. We conducted a prospective multicenter clinical trial to assess ECP response rates using the 2005 National Institutes of Health (NIH) consensus criteria and to assess the relationship between regulatory T cells (Tregs) and treatment response (NCT01324908). Eighty-three patients with any NIH subtype of cGVHD were enrolled, irrespective of number of prior lines of treatment, and 6 were subsequently excluded because of the absence of follow-up from cancer relapse, infection, or study withdrawal. Study outcomes were provider-assessed response and formal response by 2005 NIH criteria. Peripheral blood samples were collected at prespecified study visits and were analyzed by flow cytometry for Tregs. In a heavily pretreated cohort of patients, with a median of 2 prior lines of therapy, 62.3% of patients had a provider-assessed response to ECP and 43.5% had response by NIH criteria. These assessments showed only a slight agreement (kappa statistic, .09). In a logistic regression model that included previously identified risk factors such as bilirubin, platelet count, and time from transplant to study entry, no clinical factors were associated with the provider's response assessment. Furthermore, there was no significant difference in percentage of Tregs in blood leukocytes at study entry and completion or in overall change in Treg frequency between ECP responders and nonresponders. ECP was associated with a clinically significant decrease in median prednisone dose (.36 to .14 mg/kg, P < .001) from study entry to last visit and a significant decrease in global severity of cGVHD and total body surface area with erythematous rash. Overall, ECP was able to deliver response using NIH response criteria in a highly pretreated cohort with moderate and severe cGVHD independent of most previous risk factors for adverse outcomes of cGVHD.

Successful treatment of sclerotic cutaneous graft‐versus‐host disease using extracorporeal photopheresis

“…Gandelmann et al reported that 55 % of patients with chronic cutaneous GVHD (89.6 % of the total study population) showed a response to ECP. In the subpopulation of patients with sGVHD (58 %), there was no significant improvement in sclerosis in terms of the body surface area affected [14]. It should be noted, though, that the study duration of only six months was too short for patients with sGVHD; a significant response was therefore not to be expected.…”

“…Results of prospective trials of large cohorts have been published [14,15]. In the subpopulation of patients with sGVHD (58 %), there was no significant improvement in sclerosis in terms of the body surface area affected [14]. In the subpopulation of patients with sGVHD (58 %), there was no significant improvement in sclerosis in terms of the body surface area affected [14].…”

“…The national European, British and American guidelines strongly support the use of ECP for the treatment of GVHD [2,[10][11][12][13]. Results of prospective trials of large cohorts have been published [14,15]. Gandelmann et al reported that 55 % of patients with chronic cutaneous GVHD (89.6 % of the total study population) showed a response to ECP.…”

Erfolg der extrakorporalen Photopherese bei sklerotischer Graft‐versus‐Host‐Erkrankung der Haut

“…Ergebnisse prospektiver Untersuchungen an größeren Patientenkollektiven sind publiziert [14,15]. In der Subpopulation der Patienten mit sGvHD (58 %) ergab sich bezogen auf die betroffene Körperoberfläche keine signifikante Verbesserung der Sklerose [14]. In der Subpopulation der Patienten mit sGvHD (58 %) ergab sich bezogen auf die betroffene Körperoberfläche keine signifikante Verbesserung der Sklerose [14].…”

“…Die nationalen europäischen, britischen als auch amerikanischen Leitlinien sprechen sich deutlich für den Einsatz der ECP bei einer GvHD aus [2,[10][11][12][13]. Ergebnisse prospektiver Untersuchungen an größeren Patientenkollektiven sind publiziert [14,15]. Gandelmann et al konnten zeigen, dass insgesamt bei 55 % aller behandelten Patienten mit einer chronisch kutanen GvHD (89,6 % des Gesamtkollektivs) ein Ansprechen zu verzeichnen war.…”