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Background/Objectives: Extracorporeal photopheresis (ECP) is a well-established and efficacious cell therapy for a range of diseases. The objective of this retrospective study was to compare the new Amicus Blue inline system with the Therakos Cellex inline system and the Spectra Optia offline system in terms of collection efficiency, mononuclear cell (MNC) yield of mononuclear cell products (MCPs), processing time and correlation between MCP cell count and peripheral blood count of patients. Methods: This retrospective study compared 127 procedures utilizing the Spectra Optia offline system, 93 procedures employing the Amicus Blue inline system, and 81 procedures applying the Therakos Cellex inline system. The MNCs were subjected to flow cytometry analysis for CD45 and CD14 expression in order to ascertain the precise composition of the collected lymphocyte and monocyte fractions. Results: The Therakos inline system demonstrated the highest MNC collection efficiency (Therakos: 74.42 ± 1.82; Optia: 65.79 ± 1.48; Amicus: 56.32 ± 2.80; p < 0.01). Regarding the content of collected MNCs (×10⁶/kg body weight), the Spectra Optia offline system was superior to the other systems (Optia: 42.69 ± 1.42; Therakos: 31.21 ± 1.66; Amicus: 27.56 ± 1.54; p < 0.01). Conclusions: This study represents the first direct comparison of the new Amicus Blue inline system with the two most commonly used ECP systems in the same patient cohort of a single center. The data show that the Amicus Blue inline system collects sufficient MNCs to perform an ECP, but it has a significantly lower CE than the other systems and a significantly lower amount of collected MNCs than the Spectra Optia offline system. [ABSTRACT FROM AUTHOR]

Introduction: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. Methods: A multi‐institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID‐19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. Results: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC‐A) and red blood cell exchange (RCE). CAR‐T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID‐19 pandemic, were common and most often addressed using overtime. Discussion: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. Conclusion: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers. [ABSTRACT FROM AUTHOR]

Background Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients.Methods A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months.Results The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months (N = 22), 75.0% at 9 months (N = 24), and 60.0% at 12 months (N = 15) after ECP initiation.Conclusions Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.

Background/Objectives: Extracorporeal photopheresis (ECP) is a well-established and efficacious cell therapy for a range of diseases. The objective of this retrospective study was to compare the new Amicus Blue inline system with the Therakos Cellex inline system and the Spectra Optia offline system in terms of collection efficiency, mononuclear cell (MNC) yield of mononuclear cell products (MCPs), processing time and correlation between MCP cell count and peripheral blood count of patients. Methods: This retrospective study compared 127 procedures utilizing the Spectra Optia offline system, 93 procedures employing the Amicus Blue inline system, and 81 procedures applying the Therakos Cellex inline system. The MNCs were subjected to flow cytometry analysis for CD45 and CD14 expression in order to ascertain the precise composition of the collected lymphocyte and monocyte fractions. Results: The Therakos inline system demonstrated the highest MNC collection efficiency (Therakos: 74.42 ± 1.82; Optia: 65.79 ± 1.48; Amicus: 56.32 ± 2.80; p < 0.01). Regarding the content of collected MNCs (×10⁶/kg body weight), the Spectra Optia offline system was superior to the other systems (Optia: 42.69 ± 1.42; Therakos: 31.21 ± 1.66; Amicus: 27.56 ± 1.54; p < 0.01). Conclusions: This study represents the first direct comparison of the new Amicus Blue inline system with the two most commonly used ECP systems in the same patient cohort of a single center. The data show that the Amicus Blue inline system collects sufficient MNCs to perform an ECP, but it has a significantly lower CE than the other systems and a significantly lower amount of collected MNCs than the Spectra Optia offline system.

Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant rejection by modulating the recipient's own blood cells. We sought to induce donor-specific hypo-responsiveness of SOT recipients by infusing ECP-treated donor leukocytes prior to transplant. To this end, we utilized major histocompatibility complex mismatched rodent models of allogeneic cardiac, liver, and kidney transplantation to test this novel strategy. Leukocytes isolated from donor-matched spleens for ECP treatment (ECP-DL) were infused into transplant recipients seven days prior to SOT. Pre-transplant infusion of ECP-DL without additional IS was associated with prolonged graft survival in all models. This innovative approach promoted the production of tolerogenic dendritic cells and regulatory T-cells with subsequent inhibition of T-cell priming and differentiation, along with a significant reduction of donor-specific T-cells in the spleen and grafts of treated animals. This new application of donor-type ECP-treated leukocytes provides insight into the mechanisms behind ECP-induced immunoregulation and holds significant promise in the prevention of graft rejection and reduction in need of global immune suppressive therapy in patients following SOT.

Background: A common required duty of pathology resident physicians while rotating on transfusion medicine is the medical oversight of the therapeutic apheresis service. A task often performed on this clinical medicine service is formulating and writing orders for therapeutic apheresis procedures. The EpicCare tool called the therapy plan provides unique advantages over a standard electronic order set for therapeutic apheresis. Materials and Methods: Transfusion medicine physicians, apheresis nurses, pharmacists, and information technology professionals collaborated to create therapy plans for three therapeutic apheresis procedures: plasmapheresis, red cell exchange, and photopheresis. Results: Therapy plans were implemented and have been well‐received for several years. Over a six‐year time period, a total of 613 therapy plans were created and signed. We speculate that this implementation may have increased both physician efficiency and patient safety. Conclusion: This article reports our experience using therapy plans in EpicCare in order to raise awareness of this tool and to serve as an encouragement for wider adoption. [ABSTRACT FROM AUTHOR]

Background and Objectives: Extracorporeal photopheresis (ECP) is a widespread cellular therapy for graft‐versus‐host disease, autoimmune diseases and Sézary disease. One of the main effects of ECP is the apoptosis of leukocytes, but the therapeutic mechanisms are not completely known. The aim of this study was to investigate the effects on red blood cells, platelets and the induction of reactive oxygen species. Materials and Methods: We used human cells from healthy blood donors to simulate in vitro the composition in an apheresis bag. Cells were treated with 8‐methoxypsoralen (8‐MOP) and UVA. Red blood cell stability, platelet activity and induction of reactive oxygen species were analysed. Results: After 8‐MOP and UVA treatment, the red blood cells showed high cell integrity with low levels of eryptosis and no increase of free haemoglobin or red blood cell distribution width (RDW). Red blood cell immune‐associated antigens CD59 and CD147 were hardly affected by the treatment. Platelet glycoproteins CD41, CD62P and CD63 indicated strong platelet activation after 8‐MOP and UVA treatment. Reactive oxygen species were slightly but not significantly induced by the treatment. Conclusion: The effect of the ECP therapy is probably not exclusively mediated by leukocytes. Platelet activation is another striking effect caused by the treatment of the apheresis product with 8‐MOP/UVA. However, since we could hardly identify any evidence for eryptosis or haemolysis, it is unlikely that red blood cell eryptosis is part of the therapeutic mechanism. Further research on this topic seems to be promising. [ABSTRACT FROM AUTHOR]

Introduction: Although extracorporeal photopheresis (ECP) is a promising second-line therapy in the treatment of chronic graft-versus-host disease (cGVHD), its use is limited by its high cost. This study aims to describe the clinical evolution of patients who underwent ECP therapy for cGVHD and to perform an economic analysis of the therapy Methods: This was a case series between 2016 and 2020 describing the clinical response to ECP and a micro-cost analysis of the therapy using time-driven activity-based costing. Results: Six patients underwent ECP for corticosteroid-dependent cGVHD The cost per ECP session is 14,960.90 Brazilian reais (BRL), which primarily consists of the ECP kit with an activator (82.78%), followed by the hospital's physical structure (14.66%), human resources (2.48%) and exams/inputs (0.08%). The number of sessions performed ranged from 2 to 42. The total cost of the therapy per patient ranged from BRL 30,000 to 500,000. Conclusion: The response of the patient with cGVHD to treatment with ECP was variable. These micro-costing results can be used to develop remuneration and cost control strategies in hematopoietic stem cell transplantation programs, as well as in further economic studies.

Extracorporeal photopheresis is an established procedure for refractory graft-versus-host disease, a major complication associated with notable morbidity and mortality in patients with allogeneic hematopoietic stem cell transplant. Despite being implemented over a decade ago, there is scant information about potential interactions or analytical interferences with concomitant drugs in this polymedicated population. Here we report the case of a pediatric patient diagnosed with cutaneous steroid-refractory acute graft-versus-host disease after unrelated allogeneic hematopoietic stem cell transplant that was treated with photopheresis. Analytical quantification of voriconazole by HPLC-PDA the day following photopheresis treatment did not permit therapeutic drug monitoring (TDM) due to the presence of interference at the voriconazole retention time. Following investigations, it was demonstrated that the interference is likely attributable to a psoralen-based compound. The interference was not present when samples were obtained prior to photopheresis, enabling TDM. This case underscores the relevance of communication among the members of the treating team to perform reliable TDM, especially in routine clinical practice of pediatric patients with complex diseases undergoing innovative treatments. This finding is relevant to voriconazole quantification by HPLC-PDA, frequently used in laboratories based in middle-income countries.

Despite novel immunosuppressive ( IS) protocols, adverse effects of IS drugs continue to have notable negative impact on patient and cardiac allograft survival after heart transplantation (HTx). Therefore, IS regimens with less toxic side effects are sorely needed. We aimed to evaluate the efficacy of extracorporeal photopheresis (ECP) in combination with tacrolimus-based maintenance IS therapy in the treatment of allograft rejection in adult HTx recipients. Indications for ECP included acute moderate-to-severe or persistent mild cellular rejection, or mixed rejection. Twenty-two patients underwent a median of 22(2-44) ECP treatments after HTx. Median duration of ECP course was 173.5(2-466) days. No relevant adverse effects of ECP were noted. Reduction of methylprednisolone doses was safe throughout the ECP course. ECP, used in conjunction with pharmacological anti-rejection therapy, had a successful reversal of cardiac allograft rejection, decreased the rates of subsequential rejection episodes and normalized the allograft function in patients completing the ECP course. Short- and long-term survivals were excellent (91% at 1 and 5 years post-ECP) and comparable to International Society for Heart and Lung Transplantation registry data on HTx recipient overall survival. In conclusion, ECP can be safely used for the treatment and prevention of cardiac allograft rejection in conjunction with traditional IS regimen. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal photopheresis (ECP) treatment, mostly based on apheresis technology, is used for immunomodulation in various diseases such as cutaneous T‐cell lymphoma, graft versus host disease and other (auto)immune disorders. The aim of this study was to collect high cell counts and purity in shorter procedure times using an ECP off‐line system with an increased collection flow rate of 2 mL/min to a target volume of 200 mL buffy coat. Study design and methods: In this prospective study, data of routinely performed off‐line photopheresis treatments were collected and analyzed at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken, to assess absolute cell counts and procedure times and to calculate collection efficiencies (CE2). Results: A total of 22 patients participated in this study. The processed blood volume was 4312 mL, the collection time 120 min, overall procedure time 157 min and the absolute cell counts of treated white blood cells (WBC) and mononuclear cells (MNC) were 5.0 and 4.3 × 109 respectively (median values). The calculated CE2 for WBC and MNC was 21.1% and 58.5%, the proportion of treated MNCs of the total number of MNCs present was 55.0%. Conclusion: The data presented in this study show high therapeutically effective cell counts collected with a high MNC purity within a shorter overall collection/procedure time due to an increased collection flow rate. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (scleroderma) (SSc) is a rare autoimmune disorder characterized by excessive production of collagen. Extracorporeal photopheresis (photochemotherapy, phototherapy) (ECP) involves repeated exposure of peripheral blood lymphocytes to ultraviolet A (UVA) radiation. The rationale for treating patients with SSc by ECP lies in its presumed immunomodulatory effects, though, rigorous data on the specific effects of ECP are limited, particularly in patients with SSc. The objective was to evaluate the effects of extracorporeal photopheresis as a treatment modality for patients with SSc. We searched the databases CENTRAL and MEDLINE on 13 March 2022 and included randomized clinical trials (RCTs) on patients diagnosed with SSc and treated with ECP. Primary outcome was the change of skin scores. We applied independent extraction and judgment by multiple observers. We conducted a meta‐analysis applying the inverse variance method and the random effects model; the main outcome measure was standard mean difference of skin scores. We identified three relevant RCTs including 162 randomized (132 analyzed) people who received ECP in a simple parallel design. Pooled data of the three studies were indifferent. We estimated a standard mean difference from baseline of −0.11 (95% confidence interval −0.45 to 0.23), p = 0.54, I2 = 0%. We did not identify serious treatment‐related adverse events. The evidence base for extracorporeal photopheresis on skin scores in patients with systemic sclerosis was not high enough to support a superior effect when compared to no treatment, sham photopheresis, or D‐penicillamine. [ABSTRACT FROM AUTHOR]

Background: Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients., Methods: A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months., Results: The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months ( N  = 22), 75.0% at 9 months ( N  = 24), and 60.0% at 12 months ( N  = 15) after ECP initiation., Conclusions: Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.

Background: The off‐line extracorporeal photopheresis (ECP) procedure requires photosensitization in an external cell therapy laboratory as per the French regulatory requirement. This regulation results in higher time and costs compared with the on‐line alternative performed entirely at the patient's bedside. Recently, full in situ execution of the off‐line procedure has been implemented in the Pitié‐Salpêtrière Hospital Hemobiotherapy Department (Paris, France). This report summarizes the center's experience regarding the organizational and costs impacts of this change compared with the on‐line procedure. Material and methods: ECP was broken down into stages, and several procedures were monitored prospectively in real‐life settings. The total costs associated with both procedures were the sum of the fixed costs and variable costs related to all stages of the procedures, nursing‐time costs, property costs, and patient‐related production loss costs. Results: Eight off‐line ECP and fourteen on‐line ECP procedures were monitored during five consecutive days. Procedure duration was not different (median 137.5 vs 154.0 minutes, P =.29). Times and costs associated with nursing were higher but offset by lower fixed costs of the off‐line ECP. Total direct costs per procedure associated with using the off‐line ECP were significantly lower than those of the on‐line procedure (459.6 ± 7.1 EUR vs 953.8 ± 6.5 EUR; P =.0002). Similar results were observed when including the costs of patient production loss. Conclusions: As a competitive time procedure, the in situ off‐line method proved to be cost‐efficient by effectively offering similar patient treatment per year compared with the on‐line procedure. [ABSTRACT FROM AUTHOR]

The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments and understanding of the biology of MF/SS have led to novel agents which may offer prolonged responses with less toxicity compared to conventional chemotherapy approaches. In this review, we discuss the efficacy and safety of new nonchemotherapy treatment options including antibody agents, small molecule inhibitors, fusion proteins, and CAR T-cell therapy. We also reflect on older immunomodulatory treatments including retinoids and histone deacetylase inhibitors. Patients with MF/SS who require systemic therapy often progress through multiple agents sequentially, thus the need for additional novel agents in the treatment armamentarium. Antibody-based therapies such as alemtuzumab are highly effective in the blood compartment of disease, while brentuximab vedotin has shown higher activity in skin and lymph nodes. Checkpoint inhibitors may play a role in treating MF/SS but may induce hyperprogression, and engineered T cells and bispecific antibodies recruiting immune effectors are being developed and may show promise in the future. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory reactions and tissue damage in the joints. Long-term drug use in clinical practice is often accompanied by adverse reactions. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy with few side effects, offering a potential and safe therapeutic alternative for RA through the induction of immune tolerance. This study aimed to investigate the therapeutic effects of ECP on RA using a collagen-induced arthritis (CIA) murine model, as well as to explore its immunomodulatory effects in vivo. Additionally, particular attention was given to the significant role of monocytes during the ECP process., Methods: A murine model of rheumatoid arthritis was established by administering two injections of bovine type II collagen to DBA/1J mice. ECP, ECP-MD (mononuclear cells were depleted during the ECP), MTX, and PBS treatment were applied to the CIA mice. During the treatment process, clinical scores and body weight changes of CIA mice were closely monitored. After six treatment sessions, micro-CT images of the hind paws from live mice were captured. Ankle joints and paws of the mice were collected and processed for histological evaluation. Spleen samples were collected to measure the Th17/Treg cells ratio, and serum samples were collected to assess cytokine and anti-type II collagen IgG levels. Monocytes and dendritic cells populations before and after ECP in vitro were detected by flow cytometry., Result: ECP therapy significantly attenuated the progression of CIA, alleviated the severity of clinical symptoms in CIA mice and effectively suppressed synovial hyperplasia, inflammation, and cartilage damage. There was an expansion in the percentage of CD3 + CD4 + CD25 + FoxP3 + Tregs and a decrease in CD3 + CD4 + IL17A + Th17 cells in vivo. Furthermore, ECP reduced the serum levels of pro-inflammatory cytokines IL-6 (53.47 ± 7.074 pg/mL vs 5.142 ± 1.779 pg/mL, P < 0.05) and IL-17A (3.077 ± 0.401 pg/mL vs 0.238 ± 0.082 pg/mlL, P < 0.0001) compared with PBS. Interestingly, the depletion of monocytes during the ECP process did not lead to any improvement in clinical symptoms or histological scores in CIA mice. Moreover, the imbalance in the Th17/Treg cells ratio became even more pronounced, accompanied by an augmented secretion of pro-inflammatory cytokines IL-6 and IL-17A. In vitro, compared with cells without ECP treatment, the proportion of CD11b + cells were significantly reduced (P < 0.01), the proportion of CD11c + cells were significantly elevated (P < 0.001) 24 h after ECP treatment. Additionally, the expression of MHC II (P < 0.0001), CD80 (P < 0.01), and CD86 (P < 0.001) was downregulated in CD11c + cells 24 h after ECP treatment., Conclusion: Our study demonstrates that ECP exhibits a therapeutic effect comparable to conventional therapy in CIA mice, and the protective mechanisms of ECP against RA involve Th17/Treg cells ratio, which result in decreased IL-6 and IL-17A. Notably, monocytes derived from CIA mice are an indispensable part to the efficacy of ECP treatment, and the proportion of monocytes decreased and the proportion of tolerogenic dendritic cells increased after ECP treatment in vitro., (© 2024. The Author(s).)

Background: CLAD (Chronic Lung Allograft Dysfunction) remains a serious complication following lung transplantation. Some evidence shows that portions of Extracorporeal Photopheresis (ECP)-treated patients improve/stabilize their graft function. In spite of that, data concerning molecular mechanisms are still lacking. Aims of our study were to assess whether ECP effects are mediated by Mononuclear Cells (MNCs) modulation in term of microRNAs (miRNAs) expression and growth factors release., Methods: Cells from leukapheresis of 16 CLAD patients, at time 0 and 6-months (10 cycles), were cultured for 48h ± PHA (10 ug/ml) or LPS (2 ug/ml). Expression levels of miR-146a-5p, miR-155-5p, miR-31-5p, miR181a-5p, miR-142-3p, miR-16-5p and miR-23b-5p in MNCs-exosomes were evaluated by qRT-PCR, while ELISA assessed different growth factors levels on culture supernatants., Results: Our result showed miR-142-3p down-regulation (p = 0.02) in MNCs of ECP-patients after the 10 cycles and after LPS stimulation (p = 0.005). We also find miR-146a-5p up-regulation in cells after the 10 cycles stimulated with LPS (p = 0.03). Connective tissue growth factor (CTGF) levels significantly decreased in MNCs supernatant (p = 0.04). The effect of ECP is translated into frequency changes of Dendritic Cell (DC) subpopulations and a slight increase in T regulatory cells (Treg) number and a significant decrease in CTGF release., Conclusions: ECP might affect regulatory T cell functions, since both miR-142 and miR-146a have been shown to be involved in the regulation of suppressor regulatory T cell functions and DCs. On the other side ECP, possibly by regulating macrophage activation, is able to significantly down modulate CTGF release., (© 2024. The Author(s).)

Background: Graft-vs-Host Disease (GVHD) is a donor immune-mediated syndrome occurring in patients who undergo an allogeneic hematopoietic cell transplant (HCT). Chronic GVHD (cGVHD) presents with complications of variable severity. Corticosteroids are standard first-line (1L) treatment, but the sequence after 1L is unclear with the availability of new treatments. This research aimed to understand real-world treatment sequencing for cGVHD., Methods: This retrospective study investigated adult patients across 7 treatment sites in Canada who had received an allogeneic HCT >18 months prior to the study, experienced cGVHD, and received systemic treatment, including extracorporeal photopheresis (ECP)., Results: A total of 77 cases were reviewed retrospectively (median age = 51 (IQR 41-62), 51% female). 59 patients remained on active systemic treatment, and among this group, the most common treatments in use were corticosteroids (47%) and ruxolitinib (47%). One patient died, and 17 patients were on non-systemic treatment after complications resolved. The median lines of treatment (LOT) received was 2 (IQR 1-3), with 39% of patients having received >2 LOT. Among patients with lung complications (n = 24), 41% had received 3 or more LOT. Among patients with scleroderma (n = 22), 77% had received 3 or more LOT, 23% of which had received 6 or more unique treatments., Conclusions: The first treatment given to cGVHD patients was corticosteroids. Ruxolitinib was the most used second-line treatment. About 40% of cGVHD patients received >2 treatments, and scleroderma was associated with more LOT. There is a need for more effective cGVHD treatment options when early treatments fail to resolve complications., Competing Interests: Declaration of competing interest This study was supported by Sanofi Canada. Dr Dennis Kim reports a relationship with Sanofi Canada Inc that includes: board membership, consulting or advisory, speaking and lecture fees, and travel reimbursement. Dr Dennis Kim reports a relationship with Novartis Pharmaceuticals Canada Inc that includes: board membership, consulting or advisory, funding grants, and speaking and lecture fees., (Copyright © 2024. Published by Elsevier Inc.)

Extracorporeal photopheresis (ECP) has proven effective in the treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. In its standard version, ECP requires leukapheresis to obtain a fraction of mononuclear cells. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient. We have developed a new ECP method that does not require leukapheresis. This paper presents a description of two clinical cases of severe refractory GVHD treated by micro-ECP., (© 2023 Wiley Periodicals LLC.)

Lichen planus (LP) is an autoimmune disorder which is characterized by long lasting, recurrent course of a disease and by poor response to treatment (including systemic corticosteroids and cytostatics). Cutaneous and mucosal LP may present in atypical forms, several can transform to cancer with statistical confidence. Earlier, we have confirmed high clinical efficacy of photopheresis — method of adoptive immunotherapy in treatment of patients with typical LP.Target: research of clinical efficacy of photopheresis in complex trearment of atypical forms of cutaneous and mucosal LP.Materials and methods. There had been carried out a study of the clinical and immunological efficacy in two groups of patients: patients receiving complex therapy, which includes photopheresis with routine therapy (delagil, doxycycline and topical corticosteroids (I groupe — 23 patients) and receiving complex therapy, which includes photopheresis with single injection of methotrexate in dose of 10 mg with routine therapy ( II groupe — 18 patients).Results. In I group of patients immunological disorders were similar with results of earlier immunological studies in patients with lypical LP, among them increase in the number of CD16+-cells. In the II groupe immunological disorders were characterized by the rise of amount and activity of CD3+CD8+-lymphocytes. The high efficacy of Group I patient treatment was accompanied by the restoration of their tolerance to the skin antigenic structures, while maintaining the possibility for transendothelial migration of CD16 + cells. The effect of the treatment in Group II patients was also pronounced; however, due to the use of methotrexate, no normalization of the patients’ immune parameters was observed.Conclusion. The data obtained confirms the high clinical efficacy of photopheresis in both groups of patients and its pathogenic validity in patients suffering from atypical lichen ruber planus.

Aim – to perform a comparative study of the long-term results of the combined use of extracorporeal photochemotherapy (photopheresis) and drug immunosuppression and standard immunosuppressive therapy in patients after kidney transplantation.Materials and methods. An open cohort randomized study was conducted, including 60 patients with chronic kidney disease stage 5D. All patients underwent single-group cadaveric kidney transplantation. Patients were randomly divided into two groups. All transplants were paired, the fi rst kidney transplant was received by the patient of the main group, the second – by comparison group. 30 patients of the main group received standard protocol of immunosuppression and 10–15 sessions of photopheresis during the fi rst six months after transplantation. All patients of the comparison group received standard immunosuppressive therapy only. End points: primary – graft loss, surrogate – the number of acute rejection episodes and infectious complications, the dynamics of creatinine blood concentration, the glomerular fi ltration rate and daily proteinuria, the dynamics of tacrolimus C0 blood concentration. To study the mechanism of photopheresis action in the late postoperative period, we evaluated the immunological parameters: subpopulation of naive T-cells (CD3+CD4+CD45RO–CD28+), the level of CD28 molecule expression (MFI) on these cells and also – subpopulation of T-regulatory cells (CD3+CD4+CD25 (Hi)CD127–).Results. The use of photopheresis leads to the graft function improvement in the late postoperative period: the creatinine concentration (p = 0.017) in the blood and daily proteinuria (p = 0.011) were lower in patients of the main group, the glomerular fi ltration rate was higher (p = 0.027). The incidence rate ratio (IRR) of rejection in the main group was signifi cantly lower than in the comparison group: 0.2509 (95% CI 0.05386, 0.9167), p = 0.0358. The risk of graft loss was also lower in the main group: IRR 0.2782 (95% CI 0.07562, 0.8657), p = 0.026, as well as the risk of infectious complications: IRR 0.3888 (95% CI 0.2754; 0, 5445), p < 0.0001. Survival rate of transplants was higher in the main group (Log Rank p = 0.009; Breslow p = 0.005). The use of photopheresis made it possible to reduce the concentration of tacrolimus in the late postoperative period (p = 0.0017) without increasing the risk of graft rejection. The photopheresis tolerogenic effect in the late postoperative period may be due to an increase in the population of T-regulatory cells with the CD3+CD4+CD25(Hi)+CD127– phenotype compared to the patients which received only standard immunosuppressive therapy (p = 0.024).Conclusion. The preventive use of photopheresis contributes to improvement of the kidney transplantation long-term outcomes. Further studies are needed to study the mechanisms of photopheresis action and markers of partial immunological tolerance to the allograft.

Background aims: Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response. Methods: To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11). Results: Overall response rate was 81% after a median of three ECP procedures (range, 2–8), including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42–174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months (range, 6–57 months) 2-year overall survival and non-relapse mortality were 74% and 11%, respectively. Conclusions: Overall, the combination of low-dose corticosteroids and ECP appear to be safe and effective for first-line treatment of skin predominant aGVHD. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal photopheresis is a therapy based on the induction of apoptosis to cells harvested from peripheral blood, followed by direct retransfusion. Currently, there are two approaches: inline procedures, where cell harvesting, 8-methoxypsoralen (8-MOP) incubation, and UV irradiation is performed with a single device, and offline procedures, with collection in one device, followed by 8-MOP incubation/UV irradiation using a second device. Study Design and Methods: In a prospective crossover study, we compared an inline (Cellex, Therakos) with an established offline procedure (Optia, Terumo, and MacoGenic G2, Macopharma) in 6 patients, focusing on cell composition and apoptosis induction after 24 h. In total, 32 photopheresis treatments per device were performed. Results: We observed an overall 2-fold higher number of apoptotic "target" cells for each patient with offline treatment. All yields were stratified per patient. Yields were compared as ratio offline/inline for CD3+ (2.5-fold), CD4+ (2-fold), CD8+ (2.8-fold), CD56+ (2.8-fold), CD19+ (1.8-fold), CD15+ (0.5-fold), and CD14+ (2.2-fold) cells. Apoptosis induction was measured after 24 h with Annexin V/7-AAD for early and late apoptosis rates of CD3+ (CD4+, CD8+) and CD56+ cells. CD3+ cells of the inline treatment had an average of 88% (26% early, 62% late) of apoptotic cells compared to 75% (34% early, 41% late) in the offline treatment. Procedure duration ranged from 80 to 100 min inline, with a maximum of 1,500 mL processed blood, and 125–140 min offline, with at least 3,000 mL processed blood, depending on blood flow. Average hematocrit levels of the products were 2.7% inline versus 1.7% offline. Conclusions: The offline procedure, as established in our department, provides more apoptotic cells for treatment. The increased number of mononuclear cells collected outweighs a slightly reduced apoptosis rate after 24 h in comparison to the inline procedure. Besides this, the final decision for one or the other procedure has to take into account additional aspects, such as peripheral white blood cell count, hematocrit, and weight of the patient, required before apheresis, extracorporeal volume, and, last but not least, overall costs. The final criterion, however, has to be the reported clinical efficacy of the system applied. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Extracorporeal photochemotherapy (ECP) that takes advantage of the immunomodulatory effects of UV light has been extensively used for many years for the treatment of several T cell–mediated diseases, including graft‐versus‐host disease (GvHD) and systemic scleroderma. Immune mechanisms that lead to the establishment of T cell tolerance in ECP‐treated patients remain poorly known. In this study, we have tested the effect of UV/psoralen‐treated BM‐derived dendritic cells, referred to as ECP‐BMDCs on the outcome of an antigen‐specific T cell‐mediated reaction, that is, contact hypersensitivity (CHS), which is mediated by CD8+ effector T cells (CD8+Teff). The intravenous (i.v.) injection of antigen‐pulsed ECP‐BMDCs in recipient C57BL/6 mice induced specific CD8+ T cells endowed with immunomodulatory properties (referred to as CD8+TECP), which prevented the priming of CD8+Teff and the development of CHS, independently of conventional CD4+ regulatory T cells. CD8+TECP mediated tolerance by inhibiting the migration and functions of skin DC and subsequently the priming of CD8+Teff. CD8+TECP displayed none of the phenotypes of the usual CD8+T regulatory cells described so far. Our results reveal an underestimated participation of CD8+ T cells to ECP‐induced immunomodulation that could explain the therapeutic effects of ECP in T cell‐mediated diseases. [ABSTRACT FROM AUTHOR]