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The Cochrane Database of Systematic... Jun 2022Chronic 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... (Review)
Review
Extracorporeal photopheresis versus alternative treatment for chronic graft-versus-host disease after haematopoietic stem cell transplantation in children and adolescents.
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.
Topics: Adolescent; Child; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 35679154
DOI: 10.1002/14651858.CD009898.pub4 -
Frontiers in Bioscience (Landmark... Jan 2009Extracorporeal photoimmunotherapy-photopheresis (ECP) is an immunomodulatory therapy, which basically consists of separating the patient's leucocyte rich plasma from the... (Review)
Review
Extracorporeal photoimmunotherapy-photopheresis (ECP) is an immunomodulatory therapy, which basically consists of separating the patient's leucocyte rich plasma from the red blood cell fraction, followed by extracorporeal administration of a photosensitizer and UVA light prior to reinfusion of the treated cells. Successful use of ECP has been reported in patients with cutaneous T cell lymphoma, the Sezary syndrome variant, graft-versus-host disease, cardiac transplant rejection and other T cell mediated/autoimmune and autoimmune diseases. Apoptosis of malignant lymphocytes and presentation of their antigens to anti-tumor CD8+ T cells with induction of an anticlonotypic response by CD8+ effector cells against the CD4+ neoplastic T cells was one of the intial mechanisms of action proposed. The exact mechanism by which ECP exerts its therapeutic effect remains to be further explored and is still uncertain. The better understanding of its mode of action and the clinical benefits of ECP are important findings that provide additional tools to increase the therapeutic armamentarium in a number of acute and chronic T cell mediated diseases.
Topics: Graft Rejection; Graft vs Host Disease; Humans; Immunotherapy; Lymphoma, T-Cell; Photopheresis; Scleroderma, Systemic; Skin Neoplasms
PubMed: 19273388
DOI: 10.2741/3566 -
Revue Medicale Suisse Mar 2018During the treatment of extracorporeal photopheresis (ECP), white blood cells are collected by apheresis and exposed to ultraviolet A after incubation with...
During the treatment of extracorporeal photopheresis (ECP), white blood cells are collected by apheresis and exposed to ultraviolet A after incubation with 8-methoxypsoralen. Although ECP was first developed for cutaneous T cell lymphoma, it has shown promising efficacy in a number of other serious conditions, like acute and chronic graft-versus-host disease, lung and cardiac transplant rejection and other autoimmune diseases. The ECP has been used for thirty years in some specialized centers but remains unknown to most of the physicians. The aim of this article is to review the practical aspects, the mode of action and the current indications of ECP.
Topics: Autoimmune Diseases; Graft vs Host Disease; Humans; Lymphoma, T-Cell, Cutaneous; Photopheresis
PubMed: 29589657
DOI: No ID Found -
Journal of Clinical Apheresis Aug 2014Extracorporeal photopheresis (ECP) has had a major impact in the treatment of various conditions in the past 25 years. Although it was initially developed for the... (Review)
Review
Extracorporeal photopheresis (ECP) has had a major impact in the treatment of various conditions in the past 25 years. Although it was initially developed for the treatment of patients with resistant cutaneous T cell lymphoma (CTCL), this therapy was later used to treat recipients of solid organs and stem cell transplants with rejection or graft-versus-host disease (GVHD), respectively. A significant number of patients with CTCL can achieve long term remission with ECP therapy. Those patients with heart or lung transplants may experience fewer or shorter rejection episodes following ECP. Furthermore, patients that respond to ECP can generally reduce the dose of immunosuppression medication, thus minimizing the morbidity caused by drugs such as corticosteroids and calcineurin inhibitors. While the exact mechanism of action of ECP is not well-understood, evidence suggests that reinfusion of the patient's apoptotic white blood cells, the ultimate product of ECP, promotes immunomodulatory events that are beneficial in patients with CTCL, transplant rejection, GVHD, and possibly other inflammatory conditions.
Topics: Anticoagulants; Apoptosis; Autoimmune Diseases; Combined Modality Therapy; Dendritic Cells; Graft Rejection; Graft vs Host Disease; Heparin; Humans; Immune Tolerance; Immunosuppressive Agents; Inflammation; Leukocytes; Lymphoma, T-Cell, Cutaneous; Photopheresis
PubMed: 24828404
DOI: 10.1002/jca.21333 -
Transfusion and Apheresis Science :... Apr 2015Small, open-label studies show promising results for ECP in the treatment of steroid-dependent and medically-refractory Crohn's disease. However, proper randomized,... (Review)
Review
Small, open-label studies show promising results for ECP in the treatment of steroid-dependent and medically-refractory Crohn's disease. However, proper randomized, sham-controlled trials have not yet been performed. Based on the proposed mechanism of action of ECP, induction of a tolerogenic T cell response, ECP should be assessed in patients with early inflammatory disease rather than those who have progressed to fibrotic or stricturing disease. Randomized, sham-controlled trials need to be performed before ECP can be incorporated into standard clinical practice for the treatment of Crohn's disease.
Topics: Blood Component Removal; Clinical Trials as Topic; Crohn Disease; Humans; Immunosuppressive Agents; Inflammation; Photopheresis; Research Design; Steroids; T-Lymphocytes; Treatment Outcome
PubMed: 25747960
DOI: 10.1016/j.transci.2015.02.006 -
European Journal of Haematology May 2020Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid-refractory graft-vs-host disease (GvHD), with a good effect to side... (Meta-Analysis)
Meta-Analysis Review
Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid-refractory graft-vs-host disease (GvHD), with a good effect to side effect profile. In this review, we present a summary of present literature and provide evidence-based treatment guidelines for ECP in GvHD. The guidelines constitute a consensus statement formed by the Nordic ECP Quality Group representing all ECP centres in the Nordic countries, and aims to facilitate harmonisation and evidence-based practice. In developing the guidelines, we firstly conducted a thorough literature search of original articles and existing guidelines. In total, we identified 26 studies for ECP use in acute GvHD and 36 in chronic GvHD. The studies were generally small, retrospective and heterogeneous regarding patient characteristics, treatment schedule and outcome assessment. In general, a majority of patients achieved partial response or better, but response rates varied by the organs affected. Head-to-head comparisons to other treatment modalities were lacking. Overall, we consider the quality of evidence to be low-moderate (GRADE) and encourage future prospective multi-armed trials to strengthen the present recommendations. However, despite limitations in evidence strength, standardised treatment schedules and regular follow-up are imperative to ensure the best possible patient outcome.
Topics: Acute Disease; Animals; Chronic Disease; Disease Management; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Photopheresis; Practice Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Transplantation, Homologous; Trauma Severity Indices
PubMed: 31908057
DOI: 10.1111/ejh.13381 -
American Journal of Cardiovascular... 2003Photopheresis (extracorporeal photochemotherapy) is an immunomodulatory therapy that entails the reinfusion of peripheral blood mononuclear cells after exposure to the... (Clinical Trial)
Clinical Trial Review
Photopheresis (extracorporeal photochemotherapy) is an immunomodulatory therapy that entails the reinfusion of peripheral blood mononuclear cells after exposure to the photoreactive agent methoxsalen and ultraviolet A (UVA) radiation. Currently available at approximately 150 treatment centers worldwide, photopheresis is approved by the US FDA for advanced-stage cutaneous T-cell lymphoma (CTCL) and has also shown promise in treating nonmalignant immune-related conditions such as organ transplant rejection, acute and chronic graft-versus-host disease, and autoimmune disorders. The precise mechanism by which photopheresis evokes clinical responses is unknown, although this modality seems capable of modulating T-cell and monocyte activity. Clinical and laboratory findings suggest that the reinfusion of peripheral blood mononuclear cells after exposure to UVA-activated methoxsalen engenders an immune response against proliferating T-cell clones. Methoxsalen is a naturally occurring furocoumarin that is biologically inert until exposed to UVA radiation at the proper wavelength, at which time it irreversibly cross-links DNA thymine bases and arrests cell proliferation. T cells isolated from the peripheral blood of patients after photopheresis demonstrate significantly increased levels of apoptosis, whereas macrophages and dendritic cells exhibit the ability to phagocytize the apoptotic T cells. It is surmised that photopheresis enhances the uptake, processing, and presentation of distinctive antigens from apoptotic pathogenic T cells by macrophages and dendritic cells leading to the induction of an anticlonotypic response by cytotoxic T cells. Induction by photopheresis of apparently opposite immune processes (i.e. upregulation of an antitumor response and downregulation of allogeneic or autoimmune responses) can be explained by its ability to target either a single malignant T-cell clone (as in CTCL) or multiple activated T-cell clones (as in organ transplant rejection, graft-versus-host disease, or autoimmune disease). Because acute inflammation and T-cell activation may be important in the pathogenesis of restenosis following percutaneous transluminal coronary angioplasty (PTCA), photopheresis was used for the first time at our center to prevent restenosis. A total of 78 patients with single-vessel coronary artery disease amenable to PTCA with or without stent deployment were enrolled, 41 in the control group and 37 in the photopheresis group. Clinical restenosis occurred in significantly less photopheresis patients than control patients (8 vs 27%; p = 0.04), with a relative risk of 0.30 (95% confidence interval, 0.09-1.00). A multicenter clinical trial following a US FDA-recommended protocol is currently underway to better determine what, if any, impact photopheresis has in preventing restenosis.
Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Humans; Photopheresis
PubMed: 14727945
DOI: 10.2165/00129784-200303010-00005 -
Transfusion and Apheresis Science :... Jun 2014Graft-versus-host disease (GvHD) is a serious complication of allogeneic hematopoietic cell transplantation causing significant morbidity and mortality. Corticosteroids... (Review)
Review
Graft-versus-host disease (GvHD) is a serious complication of allogeneic hematopoietic cell transplantation causing significant morbidity and mortality. Corticosteroids are the established first-line treatment of GvHD. Patients not responding to corticosteroids have a dismal prognosis. Extracorporeal photopheresis (ECP) has objective activity in the treatment of both acute and chronic corticosteroid-refractory GvHD patients, has an excellent safety profile and is internationally well-established. ECP has been recommended by a significant number of renowned scientific organizations as an efficient treatment option for patients with GvHD. ECP has a proven corticosteroid-sparing effect and favourably impacts on survival and quality of life of responding patients.
Topics: Acute Disease; Allografts; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Photopheresis
PubMed: 24780392
DOI: 10.1016/j.transci.2014.04.005 -
Transplantation and Cellular Therapy Jun 2023Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is... (Randomized Controlled Trial)
Randomized Controlled Trial
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is graft-versus-host disease (GVHD), causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied treatment for GVHD, owing in part to its favorable safety profile. In contrast, reports on the use of ECP to prevent GVHD are rare, and randomized controlled trials (RCTs) are lacking. We conducted an RCT to assess whether ECP applied post-transplantation could prevent the development of GVHD within the first year of transplantation. We enrolled 157 patients (age 18 to 74 years) with a hematologic malignancy undergoing their first allo-HSCT, randomized as 76 to the intervention group and 81 to the control group. ECP was initiated directly on engraftment and was planned twice weekly for 2 weeks, then once weekly for 4 weeks. GVHD, relapse, and death were analyzed by Cox regression analysis. During the first year, 45 patients in the intervention group and 52 control patients developed GVHD (hazard ratio [HR], .82; 95% confidence interval [CI], .55 to 1.22; P = .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 group (per-protocol; n = 39 of 76) and the control group (n = 77), 46% versus 68%, respectively (HR, .47; 95% CI, .27 to .80; P = .006). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR, 1.38; 95% CI, .64 to 3.01; P = .42). GVHD-free relapse-free survival, event-free survival, overall survival, and nonrelapse mortality did not differ significantly between the 2 study groups. There also was no significant difference in immune reconstitution between the 2 groups. This first intention-to-treat RCT investigating ECP as GVHD prophylaxis in allo-HSCT for hematologic malignancy does not support the use of ECP as an adjunct to standard drug-based GVHD prophylaxis.
Topics: Adolescent; Adult; Aged; Humans; Middle Aged; Young Adult; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Neoplasm Recurrence, Local; Photopheresis
PubMed: 36878428
DOI: 10.1016/j.jtct.2023.02.023 -
Hematology. American Society of... Dec 2017Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for many disease states. Despite significant improvements in strategies used... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for many disease states. Despite significant improvements in strategies used to prevent and treat acute and chronic graft-versus-host disease (a/cGVHD), they continue to negatively affect outcomes of HSCT significantly. Standard, first-line treatment consists of corticosteroids; beyond this, there is little consistency in therapeutic regimens. Current options include the addition of various immunosuppressive agents, the use of which puts patients at even higher risks for infection and other morbidities. Extracorporeal photopheresis (ECP) is a widely used cellular therapy currently approved by the US Food and Drug Administration for use in patients with cutaneous T-cell lymphoma; it involves the removal of peripherally circulating white blood cells, addition of a light sensitizer, exposure to UV light, and return of the cells to the patient. This results in a series of events ultimately culminating in transition from an inflammatory state to that of tolerance, without global immunosuppression or known long-term adverse effects. Large-scale, prospective studies of the use of ECP in patients with a/cGVHD are necessary in order to develop the optimal treatment regimens.
Topics: Acute Disease; Allografts; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Cutaneous; Photopheresis
PubMed: 29222315
DOI: 10.1182/asheducation-2017.1.639