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Second line extracorporeal photopheresis for cortico-resistant acute and chronic GVHD after allogeneic hematopoietic cell transplantation for hematological malignancies: Long-term results from a real-life study
Michallet, M., Sobh, M., Deloire, A., Revesz, D., Chelgoum, Y., El-Hamri, M., Barraco, F., Labussiere, H., Nicolini, F. E., Hequet, O.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2024;:103899
Abstract
BACKGROUND & OBJECTIVES The primary objective of this observational study was to perform an exhaustive description concerning patients receiving extracorporeal photopheresis (ECP) as second line treatment after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes. STUDY DESIGN A total of 106 patients were included, 65 (61%) males and 41 (39%) females with a median age at transplantation of 52 years (range: 20-67). ECP was initiated after transplantation either for acute GVHD [N = 25 (24%), 12 grade III and 13 grade IV] affecting skin alone (N = 5), gut alone (N = 12), gut and liver (N = 8), or chronic GVHD [N = 81 (76%), 15 (14%) limited and 66 (62%) extensive]. RESULTS Among the 25 patients treated for acute GHVD, 67% were responders and among the 81 patients with chronic GVHD, 78% were responders. Patients with acute GVHD had a median OS of 6 months with a survival probability at 2 years of 35% [95%CI: 14-56]. Patients with chronic GVHD had a median OS of 72 months with a survival probability at 2 years of 68% [95%CI: 56-78]. There was a significant difference in terms of survival for patients responding to ECP compared to non-responders in both acute and chronic GVHD forms. Acute GVHD grade III-IV, negatively impacted on OS (HR=7.77, 95%CI: 1.7-34), p = 0.007 and on disease relapse HR= 5.88, 95%CI: 1.7-20, p = 0.005. CONCLUSION We demonstrated that ECP is an effective treatment for GVHD in a good proportion of patients with high overall response rate.
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ECP versus ruxolitinib in steroid-refractory acute GVHD - a retrospective study by the EBMT transplant complications working party
Penack, O., Peczynski, C., Boreland, W., Lemaitre, J., Afanasyeva, K., Kornblit, B., Jurado, M., Martinez, C., Natale, A., Pérez-Simón, J. A., et al
Frontiers in immunology. 2023;14:1283034
Abstract
INTRODUCTION Extracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making. METHODS We asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. RESULTS 31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. DISCUSSION The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD.
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Bath psoralen plus ultraviolet-A photochemotherapy for chronic graft-versus-host disease: a retrospective cohort study
Kassem, R., Barzilai, A., Pras, E., Sizopoulou, C., Pavlotsky, F.
International journal of dermatology. 2023
Abstract
BACKGROUND Chronic graft-versus-host disease is a severe complication of allogeneic stem cell and bone marrow transplantation. First-line immunosuppressive agents, such as steroids, are used to prevent this disease; however, they have multiple side effects. Therefore, bath psoralen plus ultraviolet-A (PUVA) is an alternative second-line treatment. This study aimed to evaluate the clinical efficacy of bath PUVA for managing chronic graft-versus-host disease. METHODS This retrospective, case-control study included 14 patients with extensive cutaneous chronic graft-versus-host disease, resistant to systemic corticosteroid, treated with bath PUVA. Major and partial responses were defined as clinical improvements of >70% and 50-70%, respectively. We analyzed the graft-versus-host disease clinical presentation and timing after allogeneic stem cell and bone marrow transplantation, bath PUVA doses, background diseases, additional treatments, and adverse effects. RESULTS We observed eight major (three lichenoid and five sclerodermatoid) and six partial (three lichenoid and three sclerodermatoid) responses after a mean of 28 treatment sessions. After 6 to 25 months, four of the eight patients with sclerodermatoid lesions and all those with lichenoid lesions experienced relapse but responded to additional treatment cycles. CONCLUSIONS Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.
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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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Propensity score matching analysis comparing the efficacy and steroid tapering benefit of extracorporeal photopheresis to best available therapy in third-line or beyond treatment for chronic GvHD
Novitzky-Basso, I., Patriquin, C., Linn, S. M., Chiarello, C., Pasic, I., Lam, W., Law, A., Michelis, F. V., Gerbitz, A., Viswabandya, A., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Graft-versus host disease (GvHD) is one of the major limitations to allogeneic hematopoietic stem cell transplantation (HCT). While corticosteroids with calcineurin inhibitors are established first line-therapy for chronic graft-versus host disease (cGvHD), approximately half of cGvHD patients are refractory to corticosteroid therapy. OBJECTIVE The goal of the present study was to compare treatment outcomes of patients treated with extracorporeal photophoresis (ECP) and best available therapy (BAT) as third-line or beyond treatment for cGvHD. METHOD AND PATIENTS Using propensity-score matching (PSM), treatment outcomes were compared between ECP-treated patients (n=74) and a historical cohort of cGvHD patients treated with BAT (n=132). By adjusting for unbalanced risk factors between the groups, including GvHD severity at therapy start, acute GvHD history, and baseline corticosteroid dose, 62 patients were balanced and selected for PSM. RESULTS In the PSM cohort, the ECP group showed 70.1% 12 months' failure-free survival (FFS) rate vs 32.5% in the BAT group (p<0.0001, HR 0.214), and 93.1% 12 months' overall survival (OS) rate vs 68.1% in the BAT group (p=0.0249, HR 0.3811); multivariate analysis confirmed ECP's superior FFS and OS over BAT. General linear model analysis showed faster tapering of corticosteroids in the ECP vs BAT PSM groups in the first 6 months, and higher rates of prednisone discontinuation; the ECP group had a greater percent prednisone discontinuation by 6%, 14.9% and 22.5% at months 0, 3, and 6, respectively. CONCLUSION The current study demonstrates superior FFS, OS and steroid tapering efficacy for ECP vs BAT as third-line therapy or beyond in cGvHD patients.
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Single centre retrospective analysis of extracorporeal photopheresis (ECP) therapy in patients heavily pre-treated for chronic graft-versus-host disease (cGvHD) with steroid failure
Linn, S. M., Novitzky-Basso, I., Patriquin, C., Pasic, I., Lam, W., Law, A., Michelis, F. V., Gerbitz, A., Viswabandya, A., Lipton, J., et al
Leukemia research. 2023;134:107387
Abstract
BACKGROUND Extracorporeal photopheresis (ECP) is recommended as a second- or later-line therapy for chronic GvHD (cGvHD). Benefits include reasonable response with avoidance of intense systemic immunosuppression, which can translate into lowering the risk of systemic toxicity and opportunistic infection. METHODS We evaluated 75 patients treated with ECP for cGvHD from 2007 to 2021 at Princess Margaret Cancer Centre, and analyzed overall response rate (ORR) and clinical benefit (CB) at 3, 6 and 12 months plus other long-term treatment outcomes. RESULTS With a median follow-up of 72 months, a gradual increase in ORR was noted over time: 21% (16 out of 75 patients), 57% (36/63) and 70% (32/46) at month 3, 6 and 12, respectively. Gradual increase in CB was also observed over time with CB rate of 23% (17/75), 62% (39/63), and 76% (35/46) at months 3, 6 and 12, respectively. A total of 27 failures (36%) were noted, due to: 1) ECP resistance requiring switch to other therapy (n = 14, 19%), 2) non-relapse mortality (n = 10, 13%), 3) relapse of primary disease (n = 1, 1%) or 4) ECP procedure-related complication (n = 1, 1%, line infection), with 20 deaths (27%) observed. Failure-free survival (FFS) and overall survival (OS) rates were 68.3% and 85.9% at 12 months, respectively. After starting ECP, the proportions of patients who completely discontinued steroids were 17%, 32%, and 64% at months 3, 6 and 12, respectively. CONCLUSION ECP is an effective treatment option for heavily pre-treated cGvHD patients.
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Effects of Extracorporeal Photopheresis on Quality of Life and the Course of Diseases in Patients With Mycosis Fungoides and Graft-Versus-Host Disease: A Single-Center Analysis
Vogiatzis, R., Krüger, W., Jünger, M., Arnold, A.
Cureus. 2023;15(5):e38929
Abstract
INTRODUCTION The aim of the study was to systematically analyze the influence of extracorporeal photopheresis (ECP) on the quality of life (LQ) and the course of the disease in patients with Mycosis Fungoides (MF), as well as with Graft-versus-Host Disease (GvHD). METHODS LQ was monitored retrospectively by using the dermatology life quality index (DLQI) and Skindex-29 test before ECP onset and after the last ECP. Disease parameters were assessed by objective criteria i.e. number of associated medical drugs taken, intervals between therapeutic cycles, gradual change of the disease, and eventual side-effects and complications of ECP therapy. RESULTS Fifty-one patients were treated with ECP during 2008-19; 19 out of 51 died, and follow-up was not completed in 13 patients. Finally, treatment protocols of 671 ECP procedures were evaluated in 19 patients (10 MF; 9 GvHD). MF and GvHD subpopulations did not differ in the individual scores of LQ questions, either before the outset or after the last ECP. DLQI and Skindex-29 scores were ameliorated by the ECP therapy (p= 0.001 and p< 0.001, respectively) due to improvement of individual scores of feelings, daily/social activities (p< 0.05), and functionality (p≤ 0.05). The median interval between ECP cycles was extended from two to eight weeks (p= 0.001). Needs of GvHD patients for drugs being received for the underlying disease were reduced (p= 0.035). Two of the 10 MF patients worsened from stage IIA to IIIA. Severe or minor side effects leading to a therapy interruption were not recorded. CONCLUSION Patients with GvHD experienced a notable decrease in the administration of drugs for their underlying condition, and there were no instances of severe side effects that resulted in the discontinuation of treatment. ECP is safe and effective for the treatment of MF and GvHD.
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Effect of extracorporeal photopheresis on survival in acute graft versus host disease
Kaya, A., Erkurt, M. A., Kuku, İ, Kaya, E., Berber, İ, Biçim, S., Hidayet, E., Cırık, S., Arslan, S., Yagın, F. H., et al
Journal of clinical apheresis. 2023
Abstract
BACKGROUND Extracorporeal photopheresis (ECP) is the main non-pharmacological approach accompanying systemic medical treatments in steroid-resistant acute or chronic graft versus host disease. The study aimed to examine the effect of ECP on survival in acute graft versus host disease (aGVHD). METHODS A total of 35 patients who were followed up in the adult hematology clinic of İnönü University Turgut Özal Medical Center for aGVHD were included in the study. Stem cell transplantation and ECP application parameters that may affect the survival of the patients were examined. RESULTS In aGVHD using ECP, the degree of involvement affects survival. Involvements with a clinical and laboratory score (Glucksberg system) of 2 and above significantly reduced survival. The duration of ECP use is associated with survival. Especially, 45 days and longer use increases survival (hazard ratio, P-value <.05). The duration of steroid use was found to be effective in survival in aGVHD (P < .001). ECP administration day (P = .003), duration of steroid use (P < .001), duration of ECP use (P = .001), and grade of aGVHD (P < .001) affect survival. CONCLUSION ECP use is effective in survival in patients with aGVHD score ≥2. In patients with aGVHD, especially the use of 45 days and longer has a positive effect on survival. The duration of steroid use is associated with survival in aGVHD.
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Real-world clinical characterization, healthcare resource utilization and productivity loss in chronic graft versus host patients exposed to extracorporeal photopheresis in Sweden
Schain, F., Boissin, C., Laczik, T., Fedeli, S., Remberger, M., Blennow, O., Dykes, J., Eich, T., Jones, C., Mattsson, J., et al
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103705
Abstract
BACKGROUND Extracorporeal photopheresis (ECP) is frequently used to treat moderate-severe chronic graft versus host disease (cGVHD), however limited data exists describing ECP treatment effects on healthcare and societal costs. We aimed to characterize clinical and health economic outcomes and productivity loss in cGVHD patients exposed to ECP. METHODS We identified 2708 patients aged ≥ 18 years with a record of allogeneic hematopoietic stem cell transplantation (HSCT) in the Swedish Patient Register between 2006 and 2020. Patients exposed to ECP from 3-months post HSCT (index) were included (n= 183). Data was linked to the Prescribed Drug Register, the Cause of Death Register, and the Longitudinal Integrated Database for Health Insurance and Labor Market Studies (LISA). RESULTS The median patient age at index was 51 years (IQR1-3; 38-61). In the 3-month period before ECP initiation compared to 9-12 months post-ECP, the cumulative three-month dose per patient decreased prednisolone/prednisone (1,381 mg vs. 658 mg, p < 0.001) and cyclosporin (12,242 mg vs. 3,501 mg, p < 0.001). Infection incidence also decreased over the same period (79.2% vs 59.1%, p < 0.001). Time spent in healthcare decreased from 68.9% to 22.1% from the first and fifth follow-up year respectively, and corresponding annual healthcare cost reduced from €27,719 to €1,981. Among patients < 66 years of age, sickness-related workplace absence decreased from 73.2% to 31.9% between the first and fifth follow-up year, with median annual productivity loss decreasing from €20,358 to €7,211 per patient. CONCLUSIONS ECP was associated with reduced use of corticosteroids, immunosuppressive agents, and fewer infections. Furthermore, cost and healthcare utilization decreased over time.
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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.