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Role of extracorporeal photopheresis in the management of children with graft-vs-host disease
Asensi Cantó, P., Sanz Caballer, J., Fuentes Socorro, C., Solves Alcaína, P., Lloret Madrid, P., Solís Ruíz, J., Torres Guerola, B., de la Rubia Comos, J., Fernández Navarro, J. M., Gómez-Seguí, I.
Journal of clinical apheresis. 2022
Abstract
INTRODUCTION Graft-vs-host disease (GVHD) is a frequent cause of morbidity and mortality in allogeneic stem cell transplants. Extracorporeal photopheresis (ECP) is one of the most accepted second-line treatments, but technical issues of ECP in children might be prohibitive. MATERIALS AND METHODS Patients under 18 y of age with corticodependant or corticorefractory GVHD receiving ECP at our hospital were included in this retrospective study. ECP was performed with an in-line system (CellExTherakos) in 2013-2014 and with an off-line system (Spectra Optia) from 2015 onwards. Cumulative incidence curves were obtained to compare ECP efficacy among patients grouped by different baseline, apheresis, and disease characteristics. Significant variables on univariate analysis (Gray's test) were pooled into a multivariate analysis (Fine-Gray proportional hazard regression for competing events). RESULTS A total of 701 ECP sessions were performed on 33 patients between October 2013 and December 2021. In total, 97% of the sessions could be executed. In 8% of the sessions an incident was detected, most of them mild and related to catheter dysfunction. With a median follow-up for alive patients of 33.6 mo (range, 8-95), the composite partial and complete response cumulative incidence was 70% (95% confidence interval, 51%-82%) and the median time to maximal response was 2.8 mo (range, 0.25-9.8). Significantly lower response ratios were found in patients with hepatic, gastrointestinal, acute, or severe GVHD. The only variable that influenced response on multivariate analysis was GVHD severity. DISCUSSION ECP is feasible, safe, and effective for pediatric patients with corticorefractory or corticodependant GVHD, offering a less toxic and nonimmunosuppressive treatment option.
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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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Extracorporeal photopheresis versus standard treatment for acute 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;9(9):Cd009759
Abstract
BACKGROUND Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015. OBJECTIVES To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT. SEARCH METHODS We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE (PubMed) and Embase (Ovid) 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 sought to include randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in children and adolescents with aGvHD after HSCT. DATA COLLECTION AND ANALYSIS Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author. MAIN RESULTS We identified no additional studies in the 2021 review update, so there are still no studies that meet the criteria for inclusion in this review. AUTHORS' CONCLUSIONS The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions.
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A Prospective, Multicenter Study of Closed System Extracorporeal Photopheresis for Children With Steroid-Refractory Acute Graft-Versus-Host Disease
Kitko, C. L., Abdel-Azim, H., Carpenter, P. A., Dalle, J. H., Diaz-de-Heredia, C., Gaspari, S., Gennery, A. R., Handgretinger, R., Lawitschka, A.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Steroid-refractory (SR) acute graft-versus-host disease (aGvHD) therapy involves intensive immunosuppression, which is associated with significant infectious risk. Extracorporeal photopheresis (ECP) is used to treat SR-aGvHD and is considered to be more immunomodulatory than immunosuppressive. However, pediatric data are mostly retrospective and often involve multi-step ECP that includes apheresis followed by separate photosensitizing/reinfusion on another device. OBJECTIVE To prospectively evaluate the efficacy and safety of a single-device ECP system in children with SR-aGvHD. STUDY DESIGN Open-label, multicenter, phase 3 study of the THERAKOS® CELLEX® Photopheresis System in children/young adults aged 1 to 21 years with SR-aGvHD. Patients were treated 3 times per week for 4 weeks, then twice weekly through week 12 while maintaining standard aGvHD prophylaxis. The primary efficacy endpoint was the proportion of patients achieving overall response (OR) at day 28 without the addition of next-line systemic treatment. Secondary endpoints included the proportion of patients achieving OR at weeks 8 and 12; the mean weekly steroid dose at weeks 4, 8, and 12; and treatment-emergent adverse events (TEAEs). RESULTS Twenty-nine children (median age, 8 years) were enrolled. OR was 55% by day 28, 74% by week 8, and 79% by week 12. Progressive improvements were observed in the skin and the gastrointestinal tract. Mean steroid dose decreased from 1.54 mg/kg/day at baseline to 0.90 mg/kg/day at week 4; 35% of patients achieved >50% steroid dose reduction at week 4 and 75% achieved >50% steroid dose reduction at week 12. Of 168 TEAEs reported among 25 patients (86%), 28 (17%) events were infections and 14 (8%) events were considered to be probably treatment related (all nonserious). Of 627 ECP treatments administered in children/young adults, 68% required blood priming. Treatment-related AEs, including hypotension, hypocalcemia, central line infection, and catheter-site bruising, were rare (1 event each). Three deaths occurred and were deemed unrelated to ECP by the investigators. CONCLUSION Use of the THERAKOS® CELLEX® Photopheresis System was effective in children with SR-aGvHD, with more than half experiencing improvement by day 28 and further responses observed over 12 weeks. Very few TEAEs were attributable to ECP, and no new safety signals were observed.
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Outcomes Using Narrowband UVB Phototherapy for Acute Cutaneous Graft Versus Host Disease in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients
Snyder, A. N., Wine Lee, L., Jaroscak, J. J., Donahoo, L. B., Hudspeth, M.
Journal of pediatric hematology/oncology. 2021;43(1):e151-e153
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Thymopoiesis following HSCT; a retrospective review comparing interventions for aGVHD in a pediatric cohort
Flinn, A. M., Roberts, C. F., Slatter, M. A., Skinner, R., Robson, H., Lawrence, J., Guest, J., Gennery, A. R.
Clinical immunology (Orlando, Fla.). 2018
Abstract
Acute graft-versus-host disease (aGVHD) complicates allogeneic hematopoietic stem cell transplantation (HSCT), and is treated with topical and/or systemic corticosteroids. Systemic corticosteroids and aGVHD damage thymic tissue. We compared thymopoietic effect of topical steroid therapy, corticosteroids and extracorporeal photopheresis (ECP) in 102 pediatric allogeneic HSCT patients. We categorized patients into 4 groups: - no aGVHD, aGVHD treated with topical or systemic steroid, or ECP. Naive CD4(+)CD45RA(+)CD27(+) T-lymphocyte values at 3, 6, 9, 12months post-HSCT were recorded: for ECP patients, values were recorded at 3, 6, 9, 12months during ECP. Differences were compared using the Kruskal-Wallis test. 41 patients had no aGVHD, 23 had aGVHD treated topically or systemically (25), 13 received ECP. Rate of thymopoiesis was significantly different between all groups at all time-points post-transplant (p=0.002, p<0.001, p<0.001, p=0.001 respectively). Even mild aGVHD impairs thymopoiesis. Worst recovery was in ECP patients. Earlier institution of ECP may speed thymic recovery.