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PloS One 2024Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in...
Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to Ultra Violet A light (UVA)/8-methoxypsoralen is currently unknown. Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalen in vitro and platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatment in vitro does not induce platelet aggregation or significantly alter levels of the platelet activation markers, soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECP in vitro does not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistent in vivo.
Topics: Humans; Methoxsalen; Photopheresis; Ultraviolet Rays; Skin Neoplasms; Extracellular Vesicles
PubMed: 38416722
DOI: 10.1371/journal.pone.0293687 -
Transplantation Direct Mar 2024The benefit of extracorporeal photopheresis on the course of kidney transplant rejection is unknown. The aim of our study was to investigate the variations in...
BACKGROUND
The benefit of extracorporeal photopheresis on the course of kidney transplant rejection is unknown. The aim of our study was to investigate the variations in transcriptomics on graft biopsies when extracorporeal photopheresis was used to treat chronic humoral rejection after kidney transplantation.
METHODS
We retrospectively analyzed the mRNA expression of 770 genes of interest in graft biopsies performed before and after treatment. Eight patients received an average of 23 extracorporeal photopheresis sessions over 4 mo between the 2 biopsies.
RESULTS
Transcriptomic analysis of the graft biopsies identified a significant (adjusted < 0.05) increase in mRNA in all patients and a significant decrease in , , , and FTPA2 mRNAs in 7 of 8 patients.
CONCLUSIONS
In patients treated with extracorporeal photopheresis for chronic humoral rejection after renal transplantation, omic analysis of repeated biopsies shows a reduction in fibrotic and inflammatory transcriptomic biologicals markers.
PubMed: 38380348
DOI: 10.1097/TXD.0000000000001587 -
Indian Journal of Dermatology 2023
PubMed: 38371586
DOI: 10.4103/ijd.ijd_709_23 -
Blood Advances Jun 2024Graft-versus-host disease (GVHD) occurs in about 10% to 33% of patients receiving "allogeneic" or "autologous" chimeric antigen receptor T (CAR-T) cells after preceding...
Graft-versus-host disease (GVHD) occurs in about 10% to 33% of patients receiving "allogeneic" or "autologous" chimeric antigen receptor T (CAR-T) cells after preceding allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the substantial presence of alloreactive T cells. Extracorporeal photopheresis (ECP) shows promising clinical outcomes in the treatment of GVHD after allo-HSCT without hampering antitumor and antiviral effects. This raises an interesting question: whether ECP might constitute a new way to treat patients with GVHD after CAR T-cell therapy without compromising CAR-T cells significantly. Third-generation CD19-specific CAR-T cells were generated and an in vitro ECP protocol was established. The impact of ECP on CAR-T cells was comprehensively investigated in 2 models: the nondilution model reflects days after CAR T-cell infusion and the dilution model weeks after infusion. The therapeutic effect of ECP on GVHD was examined in an in vitro mixed lymphocyte reaction (MLR) assay. We found, ECP-treated CAR-T cells demonstrated reduced potency in inducing alloreaction compared with that of the group without ECP treatment in MLR assay. ECP could selectively induce apoptosis, thereby enriching the naive and central memory CAR-T cells with a reduced alloreactivity. The cytokine milieu of CAR-T cells could be switched from immune stimulation to immune tolerance in both models. Moreover, ECP could modulate the proliferative capacity of CAR-T cells without hampering their long-term functionality in the dilution model. In conclusion, ECP constitutes a promising treatment strategy for GVHD after allo-HSCT and CAR T-cell transfusion, as ECP reduces the alloreactivity without hampering CAR T-cell functionality.
Topics: Graft vs Host Disease; Photopheresis; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Hematopoietic Stem Cell Transplantation
PubMed: 38359409
DOI: 10.1182/bloodadvances.2023012463 -
Transplantation Proceedings Mar 2024Graft-vs-Host Disease (GVHD) is a donor immune-mediated syndrome occurring in patients who undergo an allogeneic hematopoietic cell transplant (HCT). Chronic GVHD...
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.
Topics: Adult; Humans; Female; Middle Aged; Male; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Canada; Graft vs Host Disease; Adrenal Cortex Hormones; Photopheresis; Chronic Disease; Nitriles; Pyrazoles; Pyrimidines
PubMed: 38342748
DOI: 10.1016/j.transproceed.2023.12.021 -
The Journal of Dermatological Treatment Dec 2024
Topics: Humans; Photopheresis; Retrospective Studies; Tertiary Care Centers; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms
PubMed: 38331434
DOI: 10.1080/09546634.2024.2312250 -
Journal of Health Economics and... 2024The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of...
The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of cost-effective or efficacious treatment. The aim of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard-of-care therapies for the treatment of cGVHD in Australia. The study formed part of an application to the Australian Government to reimburse ECP for these patients. A cost-utility analysis was conducted comparing ECP to standard of care, which modeled the response to treatment and disease progression of cGVHD patients in Australia. Mycophenolate, tacrolimus, and cyclosporin comprised second-line standard of care based on a survey of Australian clinicians. Health states in the model included treatment response, disease progression, and death. Transition probabilities were obtained from Australian-specific registry data and randomized controlled evidence. Quality-of-life values were applied based on treatment response. The analysis considered costs of second-line treatment and disease management including immunosuppressants, hospitalizations and subsequent therapy. Disease-specific mortality was calculated for treatment response and progression. Over a 10-year time horizon, ECP resulted in an average cost reduction of $23 999 and an incremental improvement of 1.10 quality-adjusted life-years per patient compared with standard of care. The sensitivity analysis demonstrated robustness over a range of plausible scenarios. This analysis demonstrates that ECP improves quality of life, minimizes the harms associated with immunosuppressant therapy, and is a highly cost-effective option for steroid-refractory cGVHD patients in Australia. Based in part on this analysis, ECP was listed on the Medicare Benefits Schedule for public reimbursement.
PubMed: 38312919
DOI: 10.36469/001c.92028 -
Transplant International : Official... 2023Extracorporeal photopheresis (ECP) is used by few lung transplant centers to treat chronic lung allograft dysfunction (CLAD). Although reported results suggest a...
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 ( = 0.001). In multivariable Cox regression, both stabilization (HR: 0.48, CI: 0.27-0.86, = 0.013) and response (HR: 0.11, CI: 0.04-0.35, < 0.001) to ECP were associated with survival. Absolute FEV1 at baseline was also protective (HR: 0.09, CI: 0.01-0.94, = 0.046). RAS phenotype was the only risk factor for mortality (HR: 2.11, 1.16-3.83, = 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.
Topics: Humans; Allografts; Lung Transplantation; Photopheresis; Cohort Studies
PubMed: 38282747
DOI: 10.3389/ti.2023.11551 -
Cancers Dec 2023Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As...
BACKGROUND
Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As curative approaches apart from allogeneic stem cell transplantation are lacking, establishing new treatment options, especially combination therapies, is crucial.
METHODS
This retrospective study included 11 patients with SS or MF receiving therapy with mogamulizumab in combination with ECP from four European expert centers. The response rates in the skin and blood as well as treatment use and adverse events (AE) were described.
RESULTS
8/11 patients (73%) showed an overall response (OR) in the skin. The mean mSWAT decreased from 98.2 ± 40.8 to 34.6 ± 23.8. The overall response rate (ORR) in the blood was 64% with two complete responses. During combination therapy, the mean number of Sézary cells decreased from 3365.3 × 10/L before treatment to 1268.6 × 10/L. The mean minimum known period without progress was 7.2 months in the skin and 7.6 months in the blood. The most common AEs were mogamulizumab-associated rash (MAR) (45.5%), anemia (27.3%), lymphocytopenia (27.8%), and infusion related reaction (16.7%). No AE led to treatment discontinuation.
CONCLUSIONS
Our study presents the combination of mogamulizumab and ECP as an effective therapy in the blood and skin in CTCL with good tolerability, similar to mogamulizumab monotherapy.
PubMed: 38201568
DOI: 10.3390/cancers16010141 -
Bone Marrow Transplantation Mar 2024Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between...
Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between ruxolitinib and extracorporeal photophoresis (ECP). We asked EBMT centers if they were willing to provide detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively and we included all patients between 1/2017-7/2019 treated with ECP or ruxolitinib for moderate or severe SR-cGVHD. We identified 84 and 57 patients with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-cGVHD (steroid dependent vs. refractory vs. intolerant to steroids). At day+180 after initiation of treatment for SR-cGVHD the odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.35 (95% CI = [0.64; 2.91], p = 0.43). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-cGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-cGVHD.
Topics: Humans; Retrospective Studies; Prospective Studies; Steroids; Graft vs Host Disease; Photopheresis; Chronic Disease; Hematopoietic Stem Cell Transplantation; Nitriles; Pyrazoles; Pyrimidines
PubMed: 38184740
DOI: 10.1038/s41409-023-02174-2