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Advances in Experimental Medicine and... 2017Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma... (Review)
Review
Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, UBI use declined and it has now been called "the cure that time forgot". Later studies were mostly performed by Russian workers and in other Eastern countries and the modern view in Western countries is that UBI remains highly controversial.This chapter discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. No resistance of microorganisms to UV irradiation has been reported, and multi-antibiotic resistant strains are as susceptible as their wild-type counterparts. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the blood-stream, as only 5-7% of blood volume needs to be treated with UV to produce the optimum benefit. UBI may enhance the phagocytic capacity of various phagocytic cells (neutrophils and dendritic cells), inhibit lymphocytes, and oxidize blood lipids. The oxidative nature of UBI may have mechanisms in common with ozone therapy and other oxygen therapies. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy.
Topics: Animals; Bacteria; Bacterial Infections; Bacterial Load; Blood; DNA Damage; DNA, Bacterial; Humans; Microbial Viability; Photopheresis; Treatment Outcome; Ultraviolet Rays; Ultraviolet Therapy
PubMed: 29124710
DOI: 10.1007/978-3-319-56017-5_25 -
Transfusion and Apheresis Science :... Apr 2015Chronic graft-versus-host disease (GVHD) is the most important cause of late morbidity and mortality in recipients of allogeneic blood and marrow transplantation.... (Review)
Review
Chronic graft-versus-host disease (GVHD) is the most important cause of late morbidity and mortality in recipients of allogeneic blood and marrow transplantation. Despite increased understanding of biology of chronic GVHD, treatment options remain limited and ineffective. While corticosteroids represent the backbone of initial chronic GVHD treatment, they have significant long-term toxicity and more than half of the patients require second-line therapy. Among the second-line treatments for chronic GVHD, extracorporeal photopheresis (ECP) is one of the most extensively studied modalities. While high quality studies establishing true value of ECP in chronic GVHD patients are lacking, its benefits in chronic GVHD are well documented. Its putative immunomodulatory, but not immunosuppressive, properties represent an attractive alternative to the other strategies leading to global immunosuppression and the resulting risks of opportunistic infections or malignancy relapse.
Topics: Adrenal Cortex Hormones; Adult; Animals; Bone Marrow Transplantation; Child; Chronic Disease; Graft vs Host Disease; Humans; Immunologic Factors; Immunosuppression Therapy; Immunosuppressive Agents; Photopheresis; Recurrence; Transfusion Reaction
PubMed: 25716169
DOI: 10.1016/j.transci.2015.02.002 -
Transfusion and Apheresis Science :... Dec 2022Extracorporeal photochemotherapy (ECP) is emphasized chiefly as it has a high safety profile. However, the genotoxic effects of ECP are not known. This experimental...
AIM
Extracorporeal photochemotherapy (ECP) is emphasized chiefly as it has a high safety profile. However, the genotoxic effects of ECP are not known. This experimental study aimed to assess the potential genotoxic impact of ECP treatment by the AKLIDES system, a new generation standardized and automated evaluation method.
MATERIALS AND METHODS
Buffy coats were obtained from the blood of 26 healthy volunteers, and ECP was applied to 2 j/cm2 UV-A for two hours. After the DNA isolation procedure, all slides were stained with DAPI to visualize lymphocytes, FITC for visualization of damage foci marker (γH2AX), and APC for visualization of repair foci marker (53BP1). With the AKLIDES imaging system, all parameters were evaluated.
RESULTS
Median damage marker Foci γ-H2AX before and after ECP were 11.42 and 18.65 arbitrary units, respectively (p = 0.153). Median repair marker foci 53BP1 (repair biomarker) before and after ECP were measured as 4.17 and 6.7 arbitrary units. The difference was also not statistically significant (p = 0.088). Although 58 % of cells were affected by ECP irradiation, as shown by FITC fluorescent staining, no statistical difference was found in any genotoxicity parameters.
CONCLUSION
We found an increase in the foci γ-H2AX parameter, one of the objective indicators of DNA breaks, and an increase in the foci 53BP1 parameter, which indicates the post-damage repair mechanisms after ECP. However, further in vitro, and in vivo studies are needed with large sample volumes to demonstrate the significance.
Topics: Humans; Photopheresis; Histones; Fluorescein-5-isothiocyanate; DNA Damage; Lymphocytes; Biomarkers
PubMed: 35637126
DOI: 10.1016/j.transci.2022.103472 -
American Journal of Transplantation :... Mar 2024Prevention and management of allograft rejection urgently require more effective therapeutic solutions. Current immunosuppressive therapies used in solid organ... (Review)
Review
Prevention and management of allograft rejection urgently require more effective therapeutic solutions. Current immunosuppressive therapies used in solid organ transplantation, while effective in reducing the risk of acute rejection, are associated with substantial adverse effects. There is, therefore, a need for agents that can provide immunomodulation, supporting graft tolerance, while minimizing the need for immunosuppression. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy currently recommended in international guidelines as an adjunctive treatment for the prevention and management of organ rejection in heart and lung transplantations. This article reviews clinical experience and ongoing research with ECP for organ rejection in heart and lung transplantations, as well as emerging findings in kidney and liver transplantation. ECP, due to its immunomodulatory and immunosuppressive-sparing effects, offers a potential therapeutic option in these settings, particularly in high-risk patients with comorbidities, infectious complications, or malignancies.
PubMed: 38490642
DOI: 10.1016/j.ajt.2024.03.012 -
The Yale Journal of Biology and Medicine Mar 2020Dendritic cells (DCs) are professional antigen-presenting cells, necessary for the initiation and maintenance of antigen-specific immunity and tolerance. Decades of... (Review)
Review
Dendritic cells (DCs) are professional antigen-presenting cells, necessary for the initiation and maintenance of antigen-specific immunity and tolerance. Decades of research have been driven by hopes to harness the immunological capabilities of DCs and achieve physiological partnership with the immune system for therapeutic ends. Potential applications for DC-based immunotherapy include treatments for cancer, autoimmune disorders, and infectious diseases. However, DCs have poor availability in peripheral and lymphoid tissues and have poor survivability in culture, leading to the development of multiple strategies to generate and manipulate large numbers of DCs . Among these is Extracorporeal Photopheresis (ECP), a widely used cancer immunotherapy. Recent advancements have uncovered that stimulation of monocyte-to-DC maturation via physiologic inflammatory signaling lies at the mechanistic core of ECP. Here, we describe the landscape of DC-based immunotherapy, the historical context of ECP, the current mechanistic understanding of monocyte-to-DC maturation in ECP, and the implications of this understanding on making scientifically driven improvements to modern ECP protocols and devices.
Topics: Dendritic Cells; Humans; Immunotherapy; Neoplasms; Photopheresis
PubMed: 32226344
DOI: No ID Found -
Dermatologic Therapy May 2022Extracorporeal photopheresis (ECP) is considered a safe treatment modality. We aimed to assess blood parameters including coagulation during ECP over time. We performed...
Extracorporeal photopheresis (ECP) is considered a safe treatment modality. We aimed to assess blood parameters including coagulation during ECP over time. We performed a long-term retrospective single-center chart review (laboratory parameters) of adult patients (n = 172) who had received ECP for any indication. We observed a significant decrease (p < 0.05) in erythrocytes, hemoglobin, and leukocytes compared to baseline levels after only one ECP procedure. This decrease persisted after 3-, 6-, 9-, and 12-months of ECP. A significant pathological decline of hemoglobin was observed in a higher proportion (26.4% and 25.2%, respectively) of patients after 6 (p = 0.0007) and 12 (p = 0.012) months of ECP. Mean corpuscular volume as well as hematocrit was significantly decreased at 3-, 6-, 9-, and 12-months of evaluation compared to baseline (p < 0.05). After 9 and 12 months of ECP we observed a further decline in lymphocyte counts (p < 0.05). Various coagulation parameters did not change significantly during ECP treatment. Even though not all alterations observed in peripheral blood of ECP patients in the present study were of clinical significance, risk for developing persistent anemia must be considered in patients undergoing ECP.
Topics: Adult; Blood Coagulation; Hemoglobins; Humans; Photopheresis; Retrospective Studies
PubMed: 35141988
DOI: 10.1111/dth.15366 -
The Journal of Heart and Lung... Feb 2023Chronic lung allograft dysfunction (CLAD) is a leading cause of graft loss in lung transplantation. Despite this, convincing treatment data is lacking, and protocols...
BACKGROUND
Chronic lung allograft dysfunction (CLAD) is a leading cause of graft loss in lung transplantation. Despite this, convincing treatment data is lacking, and protocols vary widely between centers. CLAD phenotypes exist, but phenotype transitioning has increased the challenge of designing clinically relevant studies. Extracorporeal photopheresis (ECP) has long been a suggested salvage treatment, but efficacy appears unpredictable. This study describes our experiences with photopheresis, using novel temporal phenotyping to illustrate the clinical course.
METHODS
Retrospective analysis of patients completing ≥3 months of ECP for CLAD between 2007 and 2022 was performed. A latent class analysis employing a mixed-effects model was performed, deriving patient subgroups based on spirometry trajectory over the 12 months prior to photopheresis until graft loss or 4 years post photopheresis initiation. The resulting temporal phenotypes were compared in terms of treatment response and survival outcomes. Linear discriminatory analysis was used to assess phenotype predictability, relying solely on data available at photopheresis initiation.
RESULTS
Data from 5,169 outpatient attendances in 373 patients was used to construct the model. Five trajectories were identified, with uniform spirometry changes evident following 6 months of photopheresis. Outcomes were poorest in Fulminant patients (N = 25, 7%) with median survival of 1 year. In the remainder, poorer lung function at initiation led to poorer outcomes. The analysis revealed important confounders, affecting both decision-making and outcome interpretation.
CONCLUSIONS
Temporal phenotyping provided novel insights into ECP treatment response in CLAD, particularly the importance of timely intervention. Limitations in % Baseline values in guiding treatment decisions warrant further analysis. Photopheresis may have a more uniform effect than previously thought. Predicting survival at ECP initiation appears feasible.
Topics: Humans; Photopheresis; Bronchiolitis Obliterans; Retrospective Studies; Lung; Treatment Outcome; Graft vs Host Disease
PubMed: 37071121
DOI: 10.1016/j.healun.2022.09.022 -
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 -
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 -
Dermatologic Clinics Oct 2015Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune... (Review)
Review
Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune response in cutaneous T-cell lymphoma (CTCL). Because of its excellent side effect profile and moderate efficacy, ECP is considered first-line therapy for erythrodermic mycosis fungoides (MF) and Sézary syndrome. Patients with a measurable but low blood tumor burden are most likely to respond to ECP, and the addition of adjunctive immunostimulatory agents may also increase response rates. There may be a role for ECP in the treatment of refractory early stage MF, but data are limited.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Humans; Immunomodulation; Methoxsalen; Mycosis Fungoides; Photopheresis; Photosensitizing Agents; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 26433848
DOI: 10.1016/j.det.2015.05.011