RESUMO
BACKGROUND: Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD. METHODS: This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24. RESULTS: A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups. CONCLUSIONS: Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.).
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Doença Enxerto-Hospedeiro/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Janus Quinases/antagonistas & inibidores , Pirazóis/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Infecções por Citomegalovirus/etiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrilas , Fotoferese , Pirazóis/efeitos adversos , Pirimidinas , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Falha de Tratamento , Adulto JovemRESUMO
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.
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MicroRNAs , Fotoferese , Humanos , MicroRNAs/genética , Lipopolissacarídeos/farmacologia , Leucócitos , Regulação para Baixo/genéticaRESUMO
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.
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Artrite Experimental , Artrite Reumatoide , Fotoferese , Camundongos , Animais , Bovinos , Interleucina-17/metabolismo , Modelos Animais de Doenças , Interleucina-6 , Camundongos Endogâmicos DBA , Artrite Reumatoide/tratamento farmacológico , Inflamação , Citocinas/metabolismo , Artrite Experimental/terapia , Colágeno Tipo II , Linfócitos T Reguladores , Células Th17RESUMO
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.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Fotoferese , Humanos , Fotoferese/métodos , Doença Enxerto-Hospedeiro/terapia , Transplante Homólogo , Doença CrônicaRESUMO
Therapeutic apheresis refers to a group of extracorporeal blood processing procedures used in the treatment of a variety of systemic diseases. These complex procedures are burdened by adverse reactions related to both procedures and underlying medical conditions. Given the importance of centralizing the collection and the analysis of information on therapeutic apheresis, the Italian National Blood Center (NBC), at the request of the Italian Scientific Society of Hemapheresis and Cell Manipulation (SIdEM), implemented the Italian Registry of Therapeutic Apheresis (IRTA) including it in the Information System of Transfusion Services (SISTRA), coordinated by the NBC. In 2022, a total of 34,702 therapeutic apheresis procedures was carried out in 8,781 patients, including paediatric patients, with an average of 3.9 procedures per patient. The 2022 IRTA data indicate that the patient with hematological and/or neurological disorders mainly turns to the apheresis centers. These results confirm the IRTA data from years 2020 and 2021. In the hematological field, the apheresis centers supply hematopoietic stem cells collection for autologous transplantation as well as mononuclear cell collection for extracorporeal photopheresis. With regard to the neurological field, myasthenia, chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome along with other neurological pathologies related to immune disorders are the most treated. In conclusion, this manuscript presents 2022 activity data of IRTA providing institutions and scientific societies with a wide range of information including type and number of therapeutic procedures, adverse events and patients' outcome.
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Remoção de Componentes Sanguíneos , Fotoferese , Humanos , Criança , Remoção de Componentes Sanguíneos/métodos , Sistema de Registros , Transplante Autólogo , ItáliaRESUMO
BACKGROUND & OBJECTIVES: The primary objective of this observational study was to perform an exhaustive description concerning patients receiving extracorporeal photopheresis (ECP) as second line treatment after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes. STUDY DESIGN: A total of 106 patients were included, 65 (61%) males and 41 (39%) females with a median age at transplantation of 52 years (range: 20-67). ECP was initiated after transplantation either for acute GVHD [N = 25 (24%), 12 grade III and 13 grade IV] affecting skin alone (N = 5), gut alone (N = 12), gut and liver (N = 8), or chronic GVHD [N = 81 (76%), 15 (14%) limited and 66 (62%) extensive]. RESULTS: Among the 25 patients treated for acute GHVD, 67% were responders and among the 81 patients with chronic GVHD, 78% were responders. Patients with acute GVHD had a median OS of 6 months with a survival probability at 2 years of 35% [95%CI: 14-56]. Patients with chronic GVHD had a median OS of 72 months with a survival probability at 2 years of 68% [95%CI: 56-78]. There was a significant difference in terms of survival for patients responding to ECP compared to non-responders in both acute and chronic GVHD forms. Acute GVHD grade III-IV, negatively impacted on OS (HR=7.77, 95%CI: 1.7-34), p = 0.007 and on disease relapse HR= 5.88, 95%CI: 1.7-20, p = 0.005. CONCLUSION: We demonstrated that ECP is an effective treatment for GVHD in a good proportion of patients with high overall response rate.
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Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Fotoferese , Humanos , Fotoferese/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Idoso , Neoplasias Hematológicas/terapia , Doença Crônica , Transplante Homólogo/métodos , Doença Aguda , Adulto JovemRESUMO
Extracorporeal photopheresis (ECP) is widely used for the treatment of cutaneous T-cell lymphoma, graft-vs-host disease, and other immune-related conditions. To avoid clotting during treatment, the ECP system used must be effectively primed with an anticoagulant. Heparin is the recommended anticoagulant for the THERAKOS CELLEX System, but acid citrate dextrose-A (ACDA) is often used. We compared system performance between these two anticoagulants for this ECP system. Deidentified data for ECP device performance were obtained at each treatment session, from automatically logged Smart Cards or labels completed by device operators. We compared the effects of ACDA or heparin on overall treatment duration, buffy coat (leukocyte) collection time, photoactivation time and the number of alarms and warnings. The variability in these parameters was also assessed. Data from 23 334 treat sessions were analyzed; ACDA was used in 34.4% and heparin in 65.6%. Overall, the ECP procedure duration, buffy coat collection time and photoactivation time were numerically similar regardless of whether ACDA or heparin was used, and regardless of needle mode. Photoactivation time variability was lower with ACDA compared with heparin in all needle modes. Among treatments that were completed automatically without any operator intervention, total treatment duration and photoactivation time were significantly reduced with ACDA use in both the double- and single-needle modes. The data presented indicate that, in both double- and single-needle modes, the THERAKOS® CELLEX® integrated ECP system performed similarly with ACDA compared to heparin, although ACDA demonstrated potential benefits in reducing variability in photoactivation time.
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Doença Enxerto-Hospedeiro , Fotoferese , Neoplasias Cutâneas , Humanos , Heparina/uso terapêutico , Fotoferese/métodos , Doença Enxerto-Hospedeiro/terapia , Anticoagulantes/uso terapêuticoRESUMO
BACKGROUND: Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment. METHODS: We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment. RESULTS: Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months). CONCLUSION: In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.
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Transplante de Pulmão , Fotoferese , Humanos , Fotoferese/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Aloenxertos , Doença Crônica , Recidiva , Disfunção Primária do Enxerto/terapia , Disfunção Primária do Enxerto/mortalidadeRESUMO
Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary's syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP's ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases.
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Remoção de Componentes Sanguíneos , Micose Fungoide , Fotoferese , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Fotoferese/métodos , Neoplasias Cutâneas/patologia , Micose Fungoide/patologia , Remoção de Componentes Sanguíneos/métodos , Síndrome de Sézary/terapiaRESUMO
Patients with cutaneous T-cell lymphoma with progressive disease typically undergo a series of skin-directed and systemic therapy regimens during cycles of response and relapse. Extracorporeal photopheresis (ECP) is an effective and safe systemic treatment option, often reserved for later stages of disease and typically employed after failure of several other therapies. ECP has benefits in response rate, time to next treatment, and tolerability that may support its use earlier in the treatment cycle for advancing/progressing disease.
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Linfoma Cutâneo de Células T , Micose Fungoide , Fotoferese , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , Recidiva Local de Neoplasia , Linfoma Cutâneo de Células T/terapia , Linfoma Cutâneo de Células T/patologiaRESUMO
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.
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Remoção de Componentes Sanguíneos , Doença Enxerto-Hospedeiro , Fotoferese , Neoplasias Cutâneas , Humanos , Fotoferese/métodos , Estudos Prospectivos , Leucócitos , Doença Enxerto-Hospedeiro/terapiaRESUMO
BACKGROUND: Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and is now beginning to be utilized in other T-cell-mediated diseases. Although ECP has been used for nearly 30â years, its mechanisms of action are not sufficiently understood, and biomarkers for response are scarce. OBJECTIVES: We aimed to investigate the immunomodulatory effects of ECP on cytokine secretion patterns in patients with L-CTCL, to help elucidate its mechanism of action. METHODS: A total of 25 patients with L-CTCL and 15 healthy donors (HDs) were enrolled in this retrospective cohort study. Concentrations of 22 cytokines were simultaneously quantified by using multiplex bead-based immunoassays. Neoplastic cells in patients' blood were evaluated by flow cytometry. RESULTS: Firstly, we observed a distinct cytokine profile pattern difference between L-CTCLs and HDs. There was a significant loss of tumour necrosis factor (TNF)-α, and significant increase of interleukins (IL)-9, IL-12 and IL-13 in the sera of patients with L-CTCL compared with HDs. Secondly, patients with L-CTCL who received ECP were classified as treatment responders and nonresponders according to the quantitative reduction of malignant burden in their blood. We evaluated cytokine levels in culture supernatants from patients' peripheral blood mononuclear cells (PBMCs) at baseline and 27 weeks after ECP initiation. Strikingly, PBMCs purified from ECP responders released statistically higher concentrations of innate immune cytokines IL-1α, IL-1ß, granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-α in comparison with ECP nonresponders. In parallel, responders showed clearance of erythema, reduction of malignant clonal T cells in the blood, and a potent boost of relevant innate immune cytokines in individual patients with L-CTCL. CONCLUSIONS: Taken together, our results demonstrate that ECP stimulates the innate immune network, and facilitates redirection of the tumour-biased immunosuppressive microenvironment towards proactive antitumour immune responses. The alterations of IL-1α, IL-1ß, GM-CSF and TNF-α can be used as biomarkers of response to ECP in patients with L-CTCL.
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Linfoma Cutâneo de Células T , Fotoferese , Neoplasias Cutâneas , Humanos , Citocinas , Fotoferese/métodos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Fator de Necrose Tumoral alfa , Estudos Retrospectivos , Leucócitos Mononucleares , Linfoma Cutâneo de Células T/patologia , Imunidade Inata , Neoplasias Cutâneas/terapia , Biomarcadores , Microambiente TumoralRESUMO
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.
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Metoxaleno , Fotoferese , Humanos , Metoxaleno/farmacologia , Espécies Reativas de Oxigênio , Plaquetas , EritrócitosRESUMO
Extracorporeal photopheresis (ECP) is used by few lung transplant centers to treat chronic lung allograft dysfunction (CLAD). Although reported results suggest a beneficial effect on CLAD progression, evidence is limited to single center experiences. The aim of this study is to analyze outcomes of ECP in a large multicenter European cohort. The primary endpoint was patient survival after initiation of ECP. This study included 631 patients, 87% suffered from bronchiolitis obliterans syndrome (BOS), and 13% had restrictive allograft syndrome (RAS). Long-term stabilization was achieved in 42%, improvement in 9%, and no response in 26%. Within the first 12 months of therapy, 23% of patients died. Patients' survival after initiation of ECP at 5 years was 56% in stable, 70% in responders, and 35% in non-responders (p = 0.001). In multivariable Cox regression, both stabilization (HR: 0.48, CI: 0.27-0.86, p = 0.013) and response (HR: 0.11, CI: 0.04-0.35, p < 0.001) to ECP were associated with survival. Absolute FEV1 at baseline was also protective (HR: 0.09, CI: 0.01-0.94, p = 0.046). RAS phenotype was the only risk factor for mortality (HR: 2.11, 1.16-3.83, p = 0.006). This study provides long-term outcomes of ECP use in CLAD patients in the largest published cohort to date. Two-thirds of the cohort had a sustained response to ECP with excellent long-term results.
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Aloenxertos , Transplante de Pulmão , Fotoferese , Humanos , Aloenxertos/fisiopatologia , Transplante de Pulmão/métodos , Fotoferese/métodos , Estudos de CoortesRESUMO
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy based on the infusion of autologous cellular products exposed to ultraviolet light (UV) in the presence of a photosensitizer. The study evaluates the ECP efficacy as induction therapy in a full-mismatch kidney transplant rat model. Dark Agouti to Lewis (DA-L) kidney transplant model has been established. ECP product was obtained from Lewis rat recipients after DA kidney graft transplantation (LewDA). Leukocytes of those LewDA rats were exposed to 8-methoxy psoralen, and illuminated with UV-A. The ECP doses assessed were 10 × 106 and 100 × 106 cells/time point. Lewis recipients received seven ECP infusions. DA-L model was characterized by the appearance of donor-specific antibodies (DSA) and kidney function deterioration from day three after kidney transplant. The dysfunction progressed rapidly until graft loss (6.1 ± 0.5 days). Tacrolimus at 0.25 mg/kg prolonged rat survival until 11.4 ± 0.7 days (p = 0.0004). In this context, the application of leukocytes from LewDA sensitized rats accelerated the rejection (8.7 ± 0.45, p = 0.0012), whereas ECP product at high dose extended kidney graft survival until 26.3 ± 7.3 days, reducing class I and II DSA in surviving rats. ECP treatment increases kidney graft survival in full-mismatch rat model of acute rejection and is a suitable immunomodulatory therapy to be explored in kidney transplantation.
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Transplante de Rim , Fotoferese , Ratos , Animais , Sobrevivência de Enxerto , Ratos Endogâmicos Lew , Rejeição de Enxerto/prevenção & controle , AnticorposRESUMO
Extracorporeal photopheresis (ECP) is a cell therapy originally employed for cutaneous T cell lymphoma and later for GvHD, solid organ rejection and other immunological diseases demonstrating an excellent safety profile. Mononuclear cell (MNCs) apoptosis triggered by UV-A light irradiation in the presence of 8-methoxypsoralene has a key role in priming the cells, ultimately leading to immunomodulation. We report preliminary data about an evaluation of the new automated irradiator device LUMILIGHT (Pelham Crescent srl) for off-line ECP. Fifteen MNCs samples collected by apheresis from 15 adult patients undergoing ECP at our Center were cultured immediately after irradiation along with untreated samples and evaluated at 24, 48 and 72 h timepoints for T cell apoptosis and viability by flow cytometry with Annexin V and Propide Iodidum staining. Post irradiation Hematocrit (HCT), calculated by the device, was compared with that of the automated cell counter. Bacterial contamination was also tested. In irradiated samples after 24-48 and 72 h, the average total apoptosis was 47 %, 70 % and 82 %, respectively, showing a significant difference from untreated samples; residual viable lymphocytes at 72 h were, on average, 18 %. The greatest initiation of apoptosis occurred from 48 h of irradiation onwards. Average early apoptosis of irradiated samples decreased over time (26 %, 17 % and 10 % at 24, 48 and 72 h, respectively). HCT measured by LUMILIGHT was over-estimated, possibly due to the low pre irradiation red blood cell contamination. Bacterial tests resulted negative. Our study showed the LUMILIGHT device to be a valid instrument for MNCs irradiation with good handling and no major technical problems as well as no adverse events in the patients. Our data need to be confirmed in larger studies.
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Remoção de Componentes Sanguíneos , Doença Enxerto-Hospedeiro , Fotoferese , Neoplasias Cutâneas , Adulto , Humanos , Fotoferese/métodos , Linfócitos , Leucócitos , Neoplasias Cutâneas/terapia , Doença Enxerto-Hospedeiro/terapiaRESUMO
In 2019, the Italian National Blood Center (NBC), at the request of the Italian Scientific Society of Haemapheresis and Cell Manipulation (SIdEM), included the Italian Registry of Therapeutic Apheresis (IRTA) in the Information System of Transfusion Services (SISTRA), whose activity is coordinated by the NBC. The IRTA provides institutions and scientific societies with a wide range of information including therapeutic procedures and outcomes of treated patients. The Italian National Health Service offers therapeutic apheresis for patients with various conditions, but it is mainly the patient with haematological and/or neurological disorders who turns to the apheresis centres as evidenced by the activity data of 2021. In the haematological field, the apheresis centres mainly supply haematopoietic stem cells for autologous or allogeneic transplantation as well as mononuclear cell collection for extracorporeal photopheresis (ECP), a therapeutic approach of II line in post-transplant Graft versus Host Disease. The activity of 2021 in the neurological field confirms the data of 2019, the pre-pandemic year, and indicates that myasthenia, chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome along with other neurological pathologies related to immune disorders are the diseases in which apheresis procedures are most used. In conclusion, the IRTA is a valuable tool for monitoring the activity of apheresis centres carried out at a national level and above all for providing an overall picture of how the use of this therapeutic tool evolves and changes over time.
Assuntos
Remoção de Componentes Sanguíneos , Doença Enxerto-Hospedeiro , Fotoferese , Humanos , Medicina Estatal , Remoção de Componentes Sanguíneos/métodos , Sistema de Registros , Itália , Doença Enxerto-Hospedeiro/etiologiaRESUMO
BACKGROUND: Extracorporeal photopheresis (ECP) is frequently used to treat moderate-severe chronic graft versus host disease (cGVHD), however limited data exists describing ECP treatment effects on healthcare and societal costs. We aimed to characterize clinical and health economic outcomes and productivity loss in cGVHD patients exposed to ECP. METHODS: We identified 2708 patients aged ≥ 18 years with a record of allogeneic hematopoietic stem cell transplantation (HSCT) in the Swedish Patient Register between 2006 and 2020. Patients exposed to ECP from 3-months post HSCT (index) were included (n= 183). Data was linked to the Prescribed Drug Register, the Cause of Death Register, and the Longitudinal Integrated Database for Health Insurance and Labor Market Studies (LISA). RESULTS: The median patient age at index was 51 years (IQR1-3; 38-61). In the 3-month period before ECP initiation compared to 9-12 months post-ECP, the cumulative three-month dose per patient decreased prednisolone/prednisone (1,381 mg vs. 658 mg, p < 0.001) and cyclosporin (12,242 mg vs. 3,501 mg, p < 0.001). Infection incidence also decreased over the same period (79.2% vs 59.1%, p < 0.001). Time spent in healthcare decreased from 68.9% to 22.1% from the first and fifth follow-up year respectively, and corresponding annual healthcare cost reduced from 27,719 to 1,981. Among patients < 66 years of age, sickness-related workplace absence decreased from 73.2% to 31.9% between the first and fifth follow-up year, with median annual productivity loss decreasing from 20,358 to 7,211 per patient. CONCLUSIONS: ECP was associated with reduced use of corticosteroids, immunosuppressive agents, and fewer infections. Furthermore, cost and healthcare utilization decreased over time.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Fotoferese , Humanos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Suécia/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aceitação pelo Paciente de Cuidados de Saúde , Doença CrônicaRESUMO
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.
Assuntos
Remoção de Componentes Sanguíneos , Medicina Clínica , Fotoferese , Humanos , Remoção de Componentes Sanguíneos/métodos , Plasmaferese/métodos , Fotoferese/métodos , Segurança do PacienteRESUMO
Extracorporeal photopheresis (ECP) has gained importance in the treatment of several diseases. Initially introduced as a new therapeutic modality for the treatment of patients with cutaneous T-cell lymphoma, the indications for the use of ECP have expanded to include hematology and transplantation immunology. Extracorporeal photopheresis has found its place in the treatment plan of cutaneous T-cell lymphoma, systemic sclerosis, graft-versus-host disease, organ transplantation such as heart and lung, sometimes as first-line therapy and very often in combination with various systemic immunosuppressive therapies. The procedure basically consists of three steps: leukapheresis, photoactivation and reinfusion. The following article presents possible theories about the mechanism of action, which is not yet fully understood, and discusses the five most common indications for ECP treatment with corresponding therapy recommendations.