Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results

Abstract

Summary:We conducted a retrospective analysis of all allogeneic stem cell transplantation (ASCT) patients started on extracorporeal photopheresis (ECP) for the management of steroid-dependent (SD) or steroid-refractory (SR) cutaneous chronic graft-versus-host disease (cGVHD) following ASCT during a 36-month period (9/98-8/01). Only SD or SR patients who were treated by ECP after day 100 and who received at least 4 weeks of ECP were considered evaluable for this analysis. Out of 64 ASCT patients reviewed, 32 patients met the inclusion criteria. All 32 patients had been previously treated with systemic corticosteroids with 11 (34%) being SR and 21 (66%) SD. Cutaneous cGVHD was extensive in 28 patients (88%) and was accompanied by visceral (hepatic, gastrointestinal) cGVHD in 23 patients (72%). The 32 evaluated patients had received a median of three prior therapies before ECP, most commonly systemic corticosteroids, tacrolimus, and mycophenolate mofetil. Patients received a median of 36 ECP sessions (range 12-98) over a median of 5.3 months (range 1-28), with a median of six sessions per month. The complete response (CR) rate was 22% (n ¼ 7) and the partial response rate was 34% (n ¼ 11). In all, 28 patients were on systemic corticosteroid therapy at ECP initiation and 18 patients achieved 50% dose reduction while on ECP, yielding a 64% steroid-sparing response rate. Of seven CRs, five are ongoing. A total of 11 (34%) patients have died after ECP, with all cases due to visceral cGVHD or cGVHD-related infectious complications. All 21 surviving patients remain on at least some immunosuppressive cGVHD therapy (including ECP in eight). Overall, ECP displays a substantial response rate and, in particular, steroid-sparing activity in SR/SD extensive cutaneous cGVHD. However, most patients continue to require at least some chronic therapy and cGVHD-related morbidity and mortality remain high.

Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease: analysis of response and survival incorporating prognostic factors

“…There may be a trend toward a higher response rate in patients with progressive, rather than de novo onset, of cGVHD. Our results are in concordance with those of Apisarnthanarax et al 38 in that there appears to be no association between dose intensity (number of ECP treatments per month) and clinical response. As the small numbers of patients in these and other published Phase II trials, it is difficult to accurately determine predictors of response to ECP.…”

“…Donor status (MRD vs MUD) appears not to correlate with response to ECP but does appear to be associated with a higher mortality rate in both our study and in that of Apisarnthanarax et al 38 The timing of initiation of ECP, early in the course of treatment for cGVHD or later (41 year from onset), was not a significant predictor of response, in contrast to Child et al 24 who noted a higher response rate in skin GVHD in patients who started ECP earlier than 1 year after onset of cGVHD. The median time from transplant to ECP was similar in our series and that of Apisarnthanarax et al 38 (24,26 months, respectively), and median time from onset of cGVHD and ECP was 17 months in the responders in both studies. As it is difficult to assess risk groups among the patients in these series, it is impossible to conclude that the efficacy of ECP is lower in patients with long-standing chronic skin and visceral GVHD.…”

“…19,20 A number of retrospective reports have demonstrated efficacy of ECP therapy in patients with skin and visceral manifestations of cGVHD, but little information is available regarding prognostic or biological variables predictive of response. 5,6,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] In this prospective study, we analyzed response and prognostic variables in 25 steroid-refractory cGVHD patients treated with ECP on a twice-or once-weekly schedule.…”

Venous thromboembolism in hematopoietic stem cell transplant recipients

“…This is a potential risk factor for thrombosis which has been reported as a reason for discontinuation of therapy. 33,34 In addition to a risk of thrombosis, HSCT recipients also have an increased risk of bleeding because of prolonged and severe thrombocytopenia. In the studies mentioned above, the rate of bleeding in HSCT recipients ranges from 15.2 to 27.1%, and life-threatening or fatal bleeding occurred in 1.1-3.6% patients.…”

Extracorporeal photochemotherapy for treatment of fasciitis in chronic graft-versus-host disease

“…4 To the best of our knowledge, this is the first case of cGVHD fasciitis treated with ECP. ECP is currently a consolidated treatment for visceral and cutaneous involvement in chronic GVHD, [5][6][7][8][9][10][11][12] and has also proven effective in cases of eosinophilic fasciitis, 10 a disease similar to cGVHD fasciitis. Although we have treated only one case, the results are encouraging.…”