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Real-World Experience in Extracorporeal photopheresisfor adults with graft-versus-host disease
Asensi Cantó, P., Sanz Caballer, J., Sopeña Pell-Ilderton, C., Solís Ruiz, J., Lloret Madrid, P., Montaner Villalba, M., Facal Malvar, A., Chorão, P., Guerreiro, M., Balaguer Roselló, A., et al
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
INTRODUCTION Extracorporeal photopheresis (ECP) has shown efficacy in graft-versus-host disease (GVHD). We aim to summarize eight years of real-world experience with off-line ECP in our institution, in order to validate this treatment schedule and analyze predictive factors. MATERIALS AND METHODS All consecutive adult patients with steroid-dependent or steroidrefractory GVHD receiving off-line ECP were included in this single center, retrospective study. ECP was performed with Spectra Optia®, processing one total blood volume, with a frequency of twice a week for acute GVHD and once a week for chronic GVHD, and tapered individually according to clinical response. Cumulative incidence of response, including complete responses (CR) and partial responses (PR), were compared among patients grouped by different baseline, apheresis and disease characteristics. RESULTS Between January 2015 and May 2022, 1382 ECP procedures were proposed for 82 patients. No incidents were reported in 97% of sessions. GVHD responded in 78% of patients (acute GVHD 57% CR and 4% PR, chronic GVHD 39% CR and 48% PR). Overall survival was statistically longer for acute GVHD patients responding to ECP than for those who did not (67.5% vs. 26% at one year, respectively; P = 0.037). Severity was an independent predictor of response in acute GVHD whereas the absence of mouth involvement and lower lymphocyte counts in the apheresis product correlated with a higher response in chronic GVHD. DISCUSSION This treatment schedule is effective for GVHD. Further investigation is required to identify ECP-specific predictive factors, as findings are not homogeneous among different studies.
PICO Summary
Population
Adults with steroid-dependent or steroid refractory GVHD from a single centre in Spain (n=82)
Intervention
Extracoroporeal photopheresis (ECP) with Spectra Optia®, processing one total blood volume, with a frequency of twice a week for acute GVHD and once a week for chronic GVHD
Comparison
None
Outcome
Between January 2015 and May 2022, 1382 ECP procedures were proposed for 82 patients. No incidents were reported in 97% of sessions. GVHD responded in 78% of patients (acute GVHD 57% complete response (CR) and 4% partial response (PR), chronic GVHD 39% CR and 48% PR). Overall survival was statistically longer for acute GVHD patients responding to ECP than for those who did not (67.5% vs. 26% at one year, respectively). Severity was an independent predictor of response in acute GVHD whereas the absence of mouth involvement and lower lymphocyte counts in the apheresis product correlated with a higher response in chronic GVHD.
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Extracorporeal photopheresis as graft-versus-host disease prophylaxis: a randomized controlled trial: Prophylactic extracorporeal photopheresis to prevent graft-versus-host disease
Ali, M. M., Gedde-Dahl, T., Osnes, L. T., Perrier, F., Veierød, M. B., Tjønnfjord, G. E., Iversen, P. O.
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for many patients diagnosed with hematological malignancies. A major obstacle is graft-versus-host disease (GvHD) causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied GvHD treatment, partly due to its favourable safety profile. In contrast, the use of ECP in preventing GvHD is sparse, and randomized controlled trials (RCTs) are lacking. OBJECTIVE We therefore conducted a RCT to assess if ECP applied post-transplant, could prevent the development of GvHD within the first year of transplantation. STUDY DESIGN We enrolled 157 patients (18-74 years) with a hematological malignancy receiving first allo-HSCT: 76 randomized to the intervention group and 81 to the control group. ECP was initiated directly upon engraftment and was planned twice weekly for two weeks, then once weekly for four weeks. GvHD, relapse, and death were analyzed with Cox regression analysis. RESULTS During the first year, 45 patients in the intervention and 52 control patients developed GvHD (HR=0.82, 95% CI 0.55-1.22, P=0.32). There were no differences in acute or chronic GvHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GvHD between the intervention (per-protocol; n=39 of 76) and the control group (n=77), 46% vs 68%, respectively, (HR 0.47, 95% CI 0.27-0.80, P=0.006). Relapse occurred in 15 patients in the intervention group and in 11 patients among the controls (HR=1.38, 95% CI 0.64-3.01, P=0.42). GvHD-free relapse-free (GRFS) survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. No significant difference in immune reconstitution between the two study groups was revealed. CONCLUSION This first intention-to-treat RCT, investigating ECP as GvHD prophylaxis in allo-HSCT for hematological malignancy does not support the use of ECP as adjunct to standard drug-based GvHD-prophylaxis. This trial was registered at www. CLINICALTRIALS gov as #NCT03204721.
PICO Summary
Population
Adults with a haematological malignancy receiving first allo-HSCT in a single centre in Norway (n=157)
Intervention
Extracorporeal photopheresis (ECP) therapy, 8 sessions over 6 weeks in addition to standard GvHD prophylaxis (n=76)
Comparison
Standard GvHD prophylaxis (n=81)
Outcome
During the first year, 45 patients in the intervention and 52 control patients developed GvHD (HR=0.82, 95% CI 0.55-1.22). There were no differences in acute or chronic GvHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GvHD between the intervention (per-protocol; n=39 of 76) and the control group (n=77), 46% vs 68%, respectively, (HR 0.47, 95% CI 0.27-0.80). Relapse occurred in 15 patients in the intervention group and in 11 patients among the controls (HR=1.38, 95% CI 0.64-3.01). GvHD-free relapse-free (GRFS) survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. No significant difference in immune reconstitution between the two study groups was revealed.
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Extracorporeal photopheresis versus alternative treatment for chronic graft-versus-host disease after haematopoietic stem cell transplantation in children and adolescents
Buder, K., Zirngibl, M., Bapistella, S., Meerpohl, J. J., Strahm, B., Bassler, D., Weitz, M.
The Cochrane database of systematic reviews. 2022;6(6):Cd009898
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Abstract
BACKGROUND Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the paediatric recipients. Currently, the therapeutic mainstay for cGvHD is treatment with corticosteroids, frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory cGvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and first updated in 2015. OBJECTIVES To evaluate the effectiveness and safety of ECP for the management of cGvHD in children and adolescents after haematopoietic stem cell transplantation. SEARCH METHODS We searched the Cochrane Register of Controlled Trials (CENTRAL) (2021), MEDLINE (PubMed) and Embase databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively. SELECTION CRITERIA We aimed to include randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in children and adolescents with cGvHD after haematopoietic stem cell transplantation. DATA COLLECTION AND ANALYSIS Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author. MAIN RESULTS We found no studies meeting the criteria for inclusion in this 2021 review update. AUTHORS' CONCLUSIONS We could not evaluate the efficacy of ECP in the treatment of cGvHD in children and adolescents after haematopoietic stem cell transplantation since the second review update again found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this population will be challenging due to the limited number of eligible participants, variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, recipients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for children and adolescents treated with ECP.
PICO Summary
Population
Children and adolescents with chronic graft-versus-host disease (GvHD) taking part in randomised controlled trials
Intervention
Extracorporeal photopheresis (ECP) with or without alternative treatment
Comparison
Alternative treatment alone
Outcome
The authors found no studies meeting the criteria for inclusion in this systematic review.
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Randomized phase II trial of extracorporeal phototherapy and steroids vs. steroids alone for newly diagnosed acute GVHD
Mehta, R. S., Bassett, R., Rondon, G., Overman, B. J., Popat, U. R., Hosing, C. M., Rezvani, K., Qazilbash, M. H., Anderlini, P., Jones, R. B., et al
Bone marrow transplantation. 2021
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Editor's Choice
Abstract
Steroids remain the initial therapy for acute graft-vs.-host disease (AGVHD). Strategies to improve response and minimize steroid exposure are needed. We report results of a randomized, adaptive, Bayesian-designed, phase II trial of prednisone with or without extracorporeal photopheresis (ECP) as an initial therapy for patients with newly diagnosed AGVHD. The primary endpoint was success at day 56 defined as: alive, in remission, achieving AGVHD response without additional therapy, and on <1?mg/kg at day 28 and <0.5?mg/kg on day 56 of steroids. Eighty-one patients were randomized to the ECP arm (n?=?51) or steroids alone (n?=?30). Median age was 54 years (range: 17-75); 90% had grade II AGVHD and 10% had grades III and IV AGVHD, with skin (85%), upper (22%)/lower (22%) gastrointestinal, and liver (10%) involvement. The ECP arm had a higher probability of success (0.815) and exceeded the predefined threshold for determining the investigational arm promising. ECP was potentially more beneficial than steroids-alone in skin-only AGVHD (response rate: 72% vs. 57%, respectively) than for visceral-organ AGVHD (47% vs. 43%, respectively). The addition of ECP to steroids may result in higher GVHD response as initial therapy for AGVHD, especially for patients with skin-only involvement.
PICO Summary
Population
Patients with newly-diagnosed acute graft-versus-host disease (AGVHD, n=81)
Intervention
Prednisone with extracorporeal photopheresis (ECP, n=51)
Comparison
Prednisone alone (n=30)
Outcome
The ECP arm had a higher probability of success (0.815) and exceeded the predefined threshold for determining the investigational arm promising. ECP was potentially more beneficial than steroids-alone in skin-only AGVHD (response rate: 72% vs. 57%, respectively) than for visceral-organ AGVHD (47% vs. 43%, respectively).
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Retrospective multicenter study of extracorporeal photopheresis in steroid-refractory acute and chronic graft-versus-host disease
Oarbeascoa, G., Lozano, M. L., Guerra, L. M., Amunarriz, C., Saavedra, C. A., Garcia-Gala, J. M., Viejo, A., Revilla, N., Fleitas, C. A., Arroyo, J. L., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
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Editor's Choice
Abstract
BACKGROUND Extracorporeal photopheresis (ECP) is an established treatment strategy in steroid-refractory GvHD. This study's main objectives were to analyze the clinical response and impact of ECP therapy in steroid dose reduction. STUDY DESIGN AND METHODS A retrospective observational series of 113 patients from 7 transplant centers was analyzed. 65 patients (58%) had acute GvHD (aGvHD) and 48 (42%) chronic GvHD (cGvHD). All ECP procedures were performed with the off-line system. RESULTS The median number of procedures until initial response was 3, for both aGvHD and cGvHD. ECP was the second-line therapy in 48% of aGvHD cases and 50% in cGvHD. 71% of the cases of aGvHD were grade 3-4 and 69% of the cases of cGvHD were severe. The overall response rate on day 28 in aGvHD was 53% (CR 45%), whereas in cGvHD it was 67% (CR 23%). Skin was the most involved organ, with a response rate of 58% (CR 49%) in aGvHD and 69% (CR 29%) in cGvHD. At the end of ECP treatment, 60% of patients treated for aGvHD that responded were able to stop steroids, with a median dose reduction of 100%. Significant OS differences were observed for patients responding to ECP in aGvHD (HR=4.3, p<0.001) and cGvHD (HR=4.8, p=0.003) patients. CONCLUSIONS ECP is a valid therapeutic alternative in patients with steroid-refractory acute and chronic GvHD, permitting significant steroid dose reductions.
PICO Summary
Population
Patients with haematological malignancies, with steroid-refractory GvHD following allo-SCT (n=113)
Intervention
Extracorporeal photopheresis
Comparison
Patients with acute GvHD (aGvHD, n=65) were compared with patients with chronic GvHD (cGvHD, n=48)
Outcome
The overall response rate on day 28 in aGvHD was 53% (CR 45%), whereas in cGvHD it was 67% (CR 23%). Skin was the most involved organ, with a response rate of 58% (CR 49%) in aGvHD and 69% (CR 29%) in cGvHD. At the end of ECP treatment, 60% of patients treated for aGvHD that responded were able to stop steroids, with a median dose reduction of 100%. Significant OS differences were observed for patients responding to ECP in aGvHD and cGvHD patients.
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Extracorporeal photopheresis as first-line strategy in the treatment of acute graft-versus-host disease after hematopoietic stem cell transplantation: a single-center experience
Sestili, S., Eder, S., Belhocine, R., Dulery, R., Battipaglia, G., Brissot, E., Mediavilla, C., Banet, A., van de Wyngaert, Z., Paviglianiti, A., et al
Cytotherapy. 2020
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Editor's Choice
Abstract
BACKGROUND AIMS Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response. METHODS To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11). RESULTS Overall response rate was 81% after a median of three ECP procedures (range, 2-8), including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42-174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months (range, 6-57 months) 2-year overall survival and non-relapse mortality were 74% and 11%, respectively. CONCLUSIONS Overall, the combination of low-dose corticosteroids and ECP appear to be safe and effective for first-line treatment of skin predominant aGVHD.
PICO Summary
Population
Adult patients with skin-predominant acute GvHD (n=37)
Intervention
Extracorporeal photopheresis (ECP) in addition to low-dose corticosteroids
Comparison
None
Outcome
Overall response rate was 81% after a median of three ECP procedures, including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42-174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months, 2-year overall survival and non-relapse mortality were 74% and 11%, respectively.