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Current Opinion in Hematology Nov 2011This article summarizes recent reports on the risks, pathogenesis and treatment of chronic graft-versus-host disease (GVHD). (Review)
Review
PURPOSE OF REVIEW
This article summarizes recent reports on the risks, pathogenesis and treatment of chronic graft-versus-host disease (GVHD).
RECENT FINDINGS
Chronic GVHD remains an elusive disorder to characterize and to treat. Recent evidence on tolerance induction by regulatory T-cells and on B-cell involvement shed some insights into the pathogenesis of chronic GVHD. In a recent large comparative study, the overall risk profiles for acute and for chronic GVHD were similar, but risk factors were not changed after adjustment for prior acute GVHD, supporting the concept that chronic GVHD is not an end stage of acute GVHD. Glucocorticoids remain the standard initial treatment of chronic GVHD, but the outcomes are not satisfactory, particularly for patients with high-risk features. Many treatments for chronic GVHD including extracorporeal photopheresis, rituximab, sirolimus, mycofenolate mofetil, imatinib, pentostatin and infusion of mesenchymal stem cells have been reported in several retrospective and relatively small phase I/II studies with a wide range of overall responses.
SUMMARY
No current therapies used for chronic GVHD have been approved by the US Food and Drug Administration. Large well designed prospective studies are warranted to establish better treatments. Targeted therapies based on the pathogenesis of chronic GVHD may lead to better outcomes.
Topics: Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Immunosuppressive Agents; Photopheresis; Risk Factors
PubMed: 21912257
DOI: 10.1097/MOH.0b013e32834ba87d -
The Journal of Heart and Lung... Aug 2023Aim of this study was to describe the real-world use of extracorporeal photopheresis (ECP) and assess its impact on clinical outcomes in the modern era of heart... (Observational Study)
Observational Study
BACKGROUND
Aim of this study was to describe the real-world use of extracorporeal photopheresis (ECP) and assess its impact on clinical outcomes in the modern era of heart transplantation.
METHODS
Seven transplant centers from 5 European countries participated in this retrospective, observational, single-arm chart review study. All patients received ECP after heart transplantation in 2015 or later. Data were extracted from medical records between November 2020 and December 2021.
RESULTS
Overall, 105 patients were enrolled and followed for an average of 2 years after initiation of ECP. Reasons to start ECP were acute cellular rejection (35.2%), rejection prevention (32.4%), mixed rejection (18.1%), and antibody-mediated rejection (14.3%). Rejection ISHLT grades improved from start to end of ECP treatment in 92% of patients treated with ECP for rejection. Of patients who started ECP to prevent rejection, 88% remained free from any rejection despite a reduction of calcineurin inhibitors. Overall survival was 95%, and no deaths were related to ECP. Safety events occurred in 18 patients, of which 13 experienced complications with venous access.
CONCLUSIONS
This study, the largest European ECP study in heart transplantation, demonstrates that ECP can effectively be used to treat different rejection types and to prevent rejection in the modern era of immunosuppression. Patients with rejections who have received ECP have shown high response as measured by histological improvements in ISHLT classification. A high percentage of patients in the prevention group remained free from rejection despite reduction in immunosuppression, in particular calcineurin inhibitors.
Topics: Humans; Photopheresis; Retrospective Studies; Calcineurin Inhibitors; Heart Transplantation; Immunosuppression Therapy; Graft Rejection
PubMed: 37037751
DOI: 10.1016/j.healun.2023.03.005 -
The Yale Journal of Biology and Medicine 1985The activation of 8-methoxypsoralen (8-MOP) by long-wavelength ultraviolet A light (UVA, 320-400 nm) induces the formation of interstrand cross-links in DNA. Psoralen...
The activation of 8-methoxypsoralen (8-MOP) by long-wavelength ultraviolet A light (UVA, 320-400 nm) induces the formation of interstrand cross-links in DNA. Psoralen plus UVA (PUVA) is widely used in the treatment of psoriasis, a hyperproliferative disease of the skin. A new psoralen plus UVA therapy has been developed in which the 8-MOP-containing blood of cutaneous T cell lymphoma (CTCL) patients is irradiated with UVA light extracorporeally (i.e., extracorporeal photopheresis). The first group of patients had the leukemic variant of CTCL. A regimen of two treatments on successive days at monthly intervals produced a clinical response in eight of 11 patients. In this review the properties of several psoralens (both naturally occurring and synthetic derivatives) are compared, using several assays (DNA cross-linking, inhibition of lymphocyte response to mitogen stimulation, and cell viability). The development of a panel of monoclonal antibodies that recognize 8-MOP-modified DNA is also described. These antibodies have been used to quantitate 8-MOP photoadduct levels in human DNA samples. In addition to the psoralens, the light activation of two other compounds, gilvocarcin and an insulin-psoralen conjugate, is described.
Topics: Animals; Antibodies, Monoclonal; DNA; Erythema; Furocoumarins; Humans; Lymphocyte Activation; Lymphocytes; Methoxsalen; Mice; Mice, Inbred BALB C; PUVA Therapy; Phototherapy; Psoriasis
PubMed: 3832664
DOI: No ID Found -
Transfusion and Apheresis Science :... Oct 2021The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL).
UNLABELLED
The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL).
MATERIAL AND METHOD
560 patients (33 % women) were treated with ECP for a total of 13,871 procedures during a 17-years period. Mean age was 48 years (±18, range 3-81 years). Self-estimation of QoL was graded: 0 (suicidal) up to 10 (best ever) and HC: 0 (Bed ridden, ICU condition) up to 10 (athletic). Adverse events were analyzed. ANOVA and paired comparisons were performed.
RESULTS
Patients were treated due to graft versus host disease (GVHD, n = 317), skin lymphoma (n = 70), solid organ transplants (n = 47), skin diseases (n = 20) and other diseases (n = 106). Adverse events (AEs) were registered in 5.4 % of the first treatments and in 1.2 % of the subsequent procedures. Severe AEs were present in 0.04 % of all procedures. No patient died due to the procedure. Tingling and stitching were the most common AE. For those with GVHD an improvement was noticed within approximately 10 procedures of ECP in the severity stage, QoL (from a mean of 6.1 to 6.8, p < 0.002) and the HC (6.1 -> 6.4, p < 0.014) and improved further with added procedures.
CONCLUSION
Photopheresis is an established therapy with few side effects. The present study of soft variables indicate that GVHD shows benefits upon ECP within approximately 10 procedures in regard to the severity of mainly skin GVHD, and lower baseline levels of HC and QoL.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Chronic Disease; Female; Graft vs Host Disease; Hemodynamics; Humans; Lymphoma; Male; Middle Aged; Photopheresis; Quality of Life; Registries; Retrospective Studies; Skin Neoplasms; Young Adult
PubMed: 34059472
DOI: 10.1016/j.transci.2021.103172 -
Journal of Clinical Immunology Jul 2021Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplant (HSCT) and negatively affects T cell... (Observational Study)
Observational Study
Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplant (HSCT) and negatively affects T cell reconstitution. Extracorporeal photopheresis (ECP) reduces aGVHD, but the mechanisms remain incompletely understood. Our objective was to examine the impact of ECP on thymopoiesis in pediatric aGVHD and the mechanisms at a cellular and transcriptional level. Sixteen pediatric HSCT patients were recruited: 6 with ECP-treated aGVHD, 5 without aGVHD, and 5 with aGVHD treated with corticosteroids only. Thymopoiesis was evaluated by measuring naive T cells, TRECs, IL-7, and T cell receptor repertoire diversity. Regulatory T cell (Treg) enumeration and function and dendritic cell (DC) enumeration and phenotype were analyzed using flow cytometry. T cell transcriptome analysis was performed on ECP patients after treatment and responders pre- and post-treatment. Four ECP responders demonstrated thymic-dependent T cell recovery, and superior median naïve T cell numbers at 8 and 12 months post-HSCT compared to the aGVHD corticosteroid group. Increased Tregs and Treg suppressive function, reduced cDC/pDC and DC co-stimulatory marker expression in ECP responders suggest upregulated peripheral tolerance; these findings were not observed in partial responders. Responder post-ECP CD3+ T cell transcriptional profile demonstrated 3333 downregulated and 364 upregulated genes, with significant downregulation of ERRα and GαS pathways, and reduced expression of pro-inflammatory and adhesion proteins.Thymic function improves with successful ECP treatment. ECP reduces T cell activation and impacts peripheral tolerance via DCs and Tregs. Differences in thymic recovery, DC, and Treg cellular patterns and the T cell transcriptome were observed between ECP responders and partial responders and require further validation and investigation in additional patients.
Topics: Adolescent; Child; Child, Preschool; Dendritic Cells; Female; Graft vs Host Disease; Humans; Infant; Interleukin-7; Male; Photopheresis; Receptors, Antigen, T-Cell; T-Lymphocytes; Thymus Gland; Transcriptome
PubMed: 33651234
DOI: 10.1007/s10875-021-00991-y -
Photochemistry and Photobiology 2014Within the last decade new technologies have been developed and implemented which employ light, often in the presence of a photosensitizer, to inactivate pathogens that... (Review)
Review
Within the last decade new technologies have been developed and implemented which employ light, often in the presence of a photosensitizer, to inactivate pathogens that reside in human blood products for the purpose of transfusion. These pathogen reduction technologies attempt to find the proper balance between pathogen kill and cell quality. Each system utilizes various chemistries that not only impact which pathogens they can inactivate and how, but also how the treatments affect the plasma and cellular proteins and to what degree. This paper aims to present the various chemical mechanisms for pathogen reduction in transfusion medicine that are currently practiced or in development.
Topics: Bacteria; Blood Transfusion; Furocoumarins; Humans; Light; Methylene Blue; Photopheresis; Photosensitizing Agents; Riboflavin; Trypanosoma; Viruses
PubMed: 25041351
DOI: 10.1111/php.12311 -
Frontiers in Immunology 2024Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are... (Review)
Review
Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.
Topics: Photopheresis; Humans; Organ Transplantation; Graft Rejection; Immunosuppression Therapy; Immunosuppressive Agents; Graft Survival
PubMed: 38846942
DOI: 10.3389/fimmu.2024.1371554 -
Blood Oct 2019
Topics: Humans; Photopheresis; Sezary Syndrome; Skin Neoplasms
PubMed: 31698438
DOI: 10.1182/blood.2019002790 -
Blood Nov 2009The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and... (Review)
Review
The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a "stage-based" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-alpha, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.
Topics: Antineoplastic Agents; Combined Modality Therapy; Humans; Mycosis Fungoides; Radiotherapy; Sezary Syndrome; Skin Neoplasms
PubMed: 19696197
DOI: 10.1182/blood-2009-07-202895 -
Current Opinion in Hematology Nov 2009Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), despite improvements in our... (Review)
Review
PURPOSE OF REVIEW
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), despite improvements in our understanding of its pathophysiology as well as the generation of new monoclonal antibodies, immunomodulatory chemotherapy, cellular therapeutics and supportive care. Herein, we review therapies that have proven effective as well as newer agents that have recently improved GVHD response rates and survival following HCT.
RECENT FINDINGS
Novel approaches to prevent or treat GVHD are often based on evidence from experimental models. Our understanding of the pathophysiology of GVHD may lead to the development of innovative strategies that target both soluble and cellular effectors. Among such agents are sirolimus, anti-tumor necrosis factor antibodies, anti-LFA-3-IgG fusion protein, extracorporeal photopheresis, mesenchymal stem cells and regulatory T cells.
SUMMARY
Obstacles to the improvement of HCT include the tight linkage between GVHD toxicity and the beneficial graft-versus-leukemia (GVL) effect, as well as the impairment of immune reconstitution by immunomodulatory drugs leading to life-threatening infections. The design of newer phase I/II clinical trials are underway. Future therapies are likely to include modulation of cell types that play key roles in the GVH process, including regulatory T cells, dendritic cells, natural killer T cells and B cells.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors
PubMed: 19812490
DOI: 10.1097/MOH.0b013e3283319a6f