Photopheresis Research Articles

Treatment of steroid-refractory acute/chronic graft versus host disease: A single-center real-world experience of ruxolitinib in combination with extracorporeal photopheresis in a high-risk population

Steroid-refractory acute and chronic graft-versus-host disease (SR-a/cGvHD) represents a potential life-threatening complication following allogeneic stem-cell transplantation (allo-SCT). The JAK1/2-inhibitor ruxolitinib and the extracorporeal photopheresis (ECP) have been shown to significantly improve the overall response rate (ORR) in this setting. However, about 30–40 % of high-risk patients do not respond to monotherapy and/or experience side effects. Considering the potential synergic mechanism of action of ruxolitinib and ECP and the good safety profile, we decided to investigate the role of a treatment strategy of ruxolitinib in combination with ECP in frail patients with high-risk SR-a/cGvHD. We conducted a retrospective single-center study comprising 47 patients who underwent allo-SCT from November 2018 to October 2023 and received treatment for SR-aGvHD (n=20) or SR-cGvHD (n=27) with ruxolitinib and ECP. In the SR-aGvHD group, 95 % of patients had a lower GI-tract involvement, with 80 % presenting with a grade III-IV SR-aGvHD. The ORR at day +28 was 65 %, with a 30 % CR rate. The 1-year overall survival (OS) for responders (PR and CR) was 33 % (95 % CI, 10 %-59 %). In the SR-cGvHD group, 55.6 % and 44.4 % had moderate and severe SR-cGvHD, respectively. The majority of patients (66.7 %) had a GI-involvement. The ORR at week 24 was 88 %, including 12 % CR and 76 % PR. The 1-year OS for responders was 76 % (95 % CI, 47 %-90 %). Our retrospective analysis shows that the treatment of ruxolitinib in combination with ECP has potential efficacy in patients with SR-a/cGvHD with a high-risk for transplantation-associated mortality.

Successful prevention of BK-polyomavirus nephropathy using extracorporeal photopheresis for immunosuppression minimisation following severe BK polyomavirus replication after kidney transplantation in a double lung transplant recipient, a case report

BackgroundBK-polyomavirus (BKpyV) nephropathy (BKVN) is associated with end-stage kidney disease in kidney and non-kidney solid organ transplantation, with no curative treatment.Case presentationA 45-year-old woman with a past medical history of double lung transplantation subsequently developed end-stage kidney disease, of undetermined origin. One month after receiving a kidney transplant, a diagnosis of early BKVN was suspected, and in retrospect was a reasonable cause for the loss of her native kidneys. Minimisation of immunosuppression, achieved through extracorporeal photopheresis, allowed clearance of BKpyV and so prevented nephropathy. Both lung and kidney grafts had a satisfactory and stable function after one year of follow-up, with no rejection.ConclusionsExtracorporeal photopheresis may have facilitated minimisation of immunosuppression and BKpyV clearance without lung allograft rejection.

Extracorporeal Photopheresis with 5-Aminolevulinic Acid in Crohn's Disease-A First-in-Human Phase I/II Study.

Background/Objectives: With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT®) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies.

A-276 Immunogenic Cell Death (ICD) and ICD-dependent Dendritic Cell Activation triggered by Extracorporeal Photopheresis in CTCL

A-276 Immunogenic Cell Death (ICD) and ICD-dependent Dendritic Cell Activation triggered by Extracorporeal Photopheresis in CTCL

A-225 The efficacy and safety of extracorporeal photopheresis (ECP) for treatment of mycosis fungoides and/or sézary syndrome in cutaneous T-cell lymphoma

A-225 The efficacy and safety of extracorporeal photopheresis (ECP) for treatment of mycosis fungoides and/or sézary syndrome in cutaneous T-cell lymphoma

A-260 Extracorporeal photopheresis leads to short-term, but not long-term changes in peripheral blood count analysis of patients with cutaneous T-cell lymphoma

A-260 Extracorporeal photopheresis leads to short-term, but not long-term changes in peripheral blood count analysis of patients with cutaneous T-cell lymphoma

P5-2 Efficacy and safety of extracorporeal photopheresis as immunotherapy for cutaneous T-cell lymphoma: a systematic review

P5-2 Efficacy and safety of extracorporeal photopheresis as immunotherapy for cutaneous T-cell lymphoma: a systematic review

Extracorporeal photopheresis vs. systemic immunosuppression for immune-related adverse events: Interim analysis of a prospective two-arm study

BackgroundCheckpoint inhibitor-induced steroid-refractory (sr) and steroid-dependent (sd) immune-related adverse events (irAE) account for about 11 % of irAE. Although these patients face worse outcomes due to irAE mortality and/or sustained immunosuppression, which impairs anti-tumor response, there is no established second-line treatment based on prospective trial data. MethodsThis prospective comparative study investigates outcomes of extracorporeal photopheresis (ECP), an immunomodulating therapy, versus second-line immunosuppressants (SLI) in sr/sd-irAE. The primary endpoint was longitudinal change in immunophenotype; secondary endpoints were outcome of irAE and tumor response. Patient demographics, quality of life (EORTC QLQ-C30; global health status (GHS/QoL)) and longitudinal blood samples were analyzed at baseline; in weeks 1, 4, 8, and 12. ResultsAt interim analysis, 21 patients (11 ECP, 10 SLI) with 7 different sr/sd-irAE were included. Compared with the SLI group, the ECP group demonstrated a higher clinical response rate of irAE (93 % vs. 80 %; 95 % CI 0.83–1.92; P = 0.54) and a better GHS/QoL score throughout all follow-up visits. ECP patients showed a numerically higher overall survival (23 vs. 12 months; 95 % CI 0.02–3.02; P = 0.27) and lower cancer progression rates (33 % vs. 67 %; 95 % CI 0.09–1.60; P = 0.52). Immunophenotyping revealed changes in immune cell populations and the regulation of immune checkpoints. There were no significant safety issues in either treatment group. ConclusionThis prospective comparative study supports the clinical efficacy of ECP in the treatment of sr/sd-irAE in comparison to the SLI cohort. Thus, ECP represents a potential treatment option for this indication, given its good safety profile while maintaining anti-tumor response. Trial RegistrationClinicalTrials.gov, NCT05700565, https://classic.clinicaltrials.gov/ct2/show/NCT05700565.

Safety and Efficacy of Extracorporeal Photopheresis for Acute and Chronic Graft-versus-Host Disease.

Background/Objectives: Despite novel biological agents, steroid-dependent or -refractory graft-versus-host disease (GvHD) remains a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT). Extracorporeal photopheresis (ECP) is an alternative, non-immunosuppressive treatment for patients with acute (aGvHD) or chronic (cGvHD) GvHD. The aim of this study was to investigate the safety and efficacy of ECP in the treatment of acute and chronic GvHD; Methods: We prospectively studied 112 patients with cGvHD who received one or more previous lines of treatment and 28 patients with steroid-dependent or refractory grade II-IV aGvHD post-alloHSCT. Results: In terms of severe aGvHD, most of the patients (19/28) responded to ECP treatment, while the five-year overall survival (OS) was 34%. After adjustment for several confounder factors, the reduction in immunosuppression (p = 0.026) and number of ECP sessions (p < 0.001) were associated with improved OS. Regarding chronic GvHD, only 19 patients failed to respond to ECP treatment; though significantly lower rates of response were presented in patients with visceral involvement (p = 0.037) and earlier post-transplant GVHD diagnosis (p = 0.001). Over a follow-up period of 45.2 [interquartile range (IQR): 5.6-345.1] months, the 5-year cumulative incidence (CI) of cGvHD-related mortality was 21.2% and was significantly reduced in patients with ECP response (p < 0.001), while the 5-year OS was 65.3%. Conclusions: Our results confirm the safety and efficacy of ECP in patients with GvHD and provide sufficient data for further investigation and the best combination drugs needed such that GvHD will not be the major barrier of allo-HCT in the near future.

Extracorporeal Photopheresis Enhances the Frequency and Function of Highly Suppressive FoxP3+ Treg Subsets in Heart Transplanted Individuals.

Extracorporeal photopheresis (ECP) has emerged as a prophylactic and therapeutic immunomodulatory option for managing acute rejection in heart transplants (HTx). The underlying mechanisms through which ECP exerts its immunomodulatory effects remain under investigation. Regulatory T cells (Treg) are a heterogeneous subset of immune lymphocytes that ensure the maintenance of tissue homeostasis, avoiding graft rejection. The transcription factor forkhead box protein 3 (FoxP3) is an essential molecular marker of Treg, acting as a "master regulator" of their genesis, stability, and functions. No study has investigated whether ECP impacts FoxP3 expression and its highly suppressive variants containing the exon 2 (FoxP3-E2), particularly in HTx. In the current study, we recruited 14 HTx participants who had undergone ECP therapy. We explored the effect of in vivo ECP on CD4+FoxP3+ Treg frequency and in vitro suppressive function in 8 HTx participants before (T0) and after 3 (T1), 6 (T2), and 12 (T3) mo of treatment. As a control group, we included 4 HTx individuals who had not undergone ECP therapy. We found that ECP increases the frequency of CD4+FoxP3+ Treg subset with highly suppressive phenotype, including CD4+FoxP3-E2+ Treg. At functional levels, we observed that ECP treatment in HTx individuals effectively improves Treg suppressive ability in controlling the proliferation of autologous conventional CD4+ T lymphocytes. Our findings collectively suggest that ECP exerts its immunomodulatory effects in HTx individuals by positively impacting the frequency and regulatory function of the FoxP3+ Treg compartment.

Current Approaches for the Prevention and Treatment of Acute and Chronic GVHD.

Whereas aGVHD has strong inflammatory components, cGVHD displays autoimmune and fibrotic features; incidence and risk factors are similar but not identical; indeed, the aGVHD is the main risk factor for cGVHD. Calcineurin Inhibitors (CNI) with either Methotrexate (MTX) or Mycophenolate (MMF) still represent the standard prophylaxis in HLA-matched allogeneic stem cell transplantation (HSCT); other strategies focused on ATG, Post-Transplant Cyclophosphamide (PTCy), Abatacept and graft manipulation. Despite the high rate, first-line treatment for aGVHD is represented by corticosteroids, and Ruxolitinib is the standard second-line therapy; investigational approaches include Microbiota transplant and the infusion of Mesenchymal stem cells. GVHD is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. It is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. Extracorporeal Photopheresis (ECP) is still an option used for steroid refractoriness or to achieve a steroid-sparing. For Ruxolitinib-refractory cGVHD, Belumosudil and Axatilimab represent the most promising agents. Bronchiolitis obliterans syndrome (BOS) still represents a challenge; among the compounds targeting non-immune effectors, Alvelestat, a Neutrophil elastase inhibitor, seems promising in BOS. Finally, in both aGVHD and cGVHD, the association of biological markers with specific disease manifestations could help refine risk stratification and the availability of reliable biomarkers for specific treatments.

Extracorporeal Photopheresis in Pediatric and Adult Patients with Graft-Versus-Host Disease.

Background/Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) resulting from histocompatibility differences between donor and host cells leading to inflammation, tissue damage, and compromised patient outcome. Extracorporeal photopheresis (ECP) is considered as a second-line treatment administered to patients with GVHD who do not respond to corticosteroid treatment or who experience a relapse after an initial response and are therefore classified as steroid refractory (SR). The aim of this study is to evaluate the clinical response rates in both pediatric and adult patients with acute (a) or chronic (c) GVHD and to assess the effectiveness of ECP using the real-world data from a single center. Methods: We performed a retrospective study on 30 patients, including 11 pediatric and 19 adult patients who were treated with ECP as a second-, third-, or fourth-line therapy for (a) and (c) GVHD, alongside corticosteroids and other immunomodulatory medications. The median time from aGVHD onset to ECP was 11.5 days (range: 3 days-9 months), while for cGVHD, the median time was 90 days (range: 2 days-9 months). Results: The overall response rate (ORR) in the aGVHD patient population was 60% with a median of 9 procedures (range: 2-20). For cGVHD patients, the ORR was 70% after a median of 23.5 ECP procedures (range: 8-43). Most patients had skin involvement, with ECP achieving an ORR of 81.8% in aGVHD and 77.7% in cGVHD cases. Conclusions: ECP is a beneficial therapy for patients with (a) and (c) GVHD who have not responded to corticosteroids and other forms of immunosuppressive therapy. Specifically, ECP demonstrated efficacy in improving skin and oral symptoms and permitted reductions in or the elimination of their corticosteroid usage. The study found that extending the duration of ECP treatment was associated with better outcomes, and no detectable complications were observed over a 38-week period.

Retrospective Single-Center Study of Extracorporeal Photopheresis as Second-Line Treatment for Chronic Graft-Versus-Host Disease

Retrospective Single-Center Study of Extracorporeal Photopheresis as Second-Line Treatment for Chronic Graft-Versus-Host Disease

CT-333 Retrospective Single-Center Study of Extracorporeal Photopheresis as Second-Line Treatment for Chronic Graft-Versus-Host Disease

CT-333 Retrospective Single-Center Study of Extracorporeal Photopheresis as Second-Line Treatment for Chronic Graft-Versus-Host Disease

Immunotherapy Prior to a Liver Transplant: Literature Review and a Case Report of Hepatocellular Carcinoma With BRCA1 Mutation

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality worldwide. The effectiveness of its standard treatment in some cases remains poor.We report a case of a patient with Barcelona Clinic Liver Cancer stage C cryptogenic HCC whose life duration was 26 months after diagnosis.A 46-year-old woman, a former smoker, presented with elevated alpha-fetoprotein and a left liver lobe mass diagnosed as HCC. Pulmonary nodules (presumably metastatic) were previously found and remained stable. The left lobe of the liver was resected. Intrahepatic recurrence developed 1.5 months later. Lenvatinib+pembrolizumab therapy was prescribed and later switched to olaparib following the detection of somatic and germline BRCA1 mutation. The patient underwent a liver transplant and was prescribed a combination of tacrolimus and everolimus, later supplemented with extracorporeal photopheresis. Pulmonary nodules that were found to be metastases were treated with radiation therapy. A lethal outcome occurred 21.3 months after the transplant.The first literature review related to this case report discusses the problem of neoadjuvant immune checkpoint inhibitor therapy prior to a liver transplant. More than 100 patients have been described in 40 articles and 113 patients, in 2 multicenter studies. Although 16.7%-27.7% of patients developed rejection, such approach may be effective in downstaging the disease.

Treatment of acute and chronic graft-versus-host disease with extracorporeal photopheresis: Update of best practice recommendations from Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and the Italian Transplant Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO)

These guidelines represent a GRADE-method revision of the recommendations produced by the Italian Society of Hemapheresis and Cell Manipulation (SIDEM) and the Italian Transplant Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) in 2013. Since 2013 several studies have been published that have strengthened the role of ECP in the management of GVHD. Thus, it was deemed appropriate to proceed with an update, with the aim to define uniform criteria for the application of ECP in adult and pediatric patients affected by GVHD throughout the national territory, in line with international guidelines, in maintaining of high standards of safety for patients and quality of the procedures provide. Post-HSCT GvHD therapies other than ECP and ECP therapy of other diseases, such as CTCL, are not covered by these guidelines.The development panel for this guideline includes professionals from various specialties who routinely interact in the management of the patient with GVHD, namely the transfusionist, the adult and pediatric hematologist, and the hospital pharmacist. A hematologist experienced in systematic reviews and GRADE guideline development ccordinated the development process, and an experienced transfusionist coordinated the assignment of tasks and reporting. External reviewers of the guideline included a patient representative.

Improving disease-specific survival for patients with Sezary syndrome in the modern era of systemic therapies.

Traditionally, Sezary syndrome (SS) has been associated with few therapeutic options and poor prognosis, with 5-year disease-specific survival (DSS) less than one-third in historical cohorts. However, newer therapies and combinations are associated with impressive time-to-next-treatment (TTNT), particularly allogeneic stem-cell transplantation (AlloSCT) and combination therapies notably those including extracorporeal photopheresis. In this multicentre, international study, we explored the prognostic outcomes of 178 patients exclusively managed for SS, diagnosed between 2012 and 2020, and treated in the modern therapeutic era. In this cohort, 58 different therapies were delivered, with 13.5% of patients receiving AlloSCT. Long-term survival exceeded historical reports with 5-year DSS and OS of 56.4% and 53.4% respectively. In those receiving AlloSCT, prognosis was excellent: 5-year DSS and OS were 90.5% and 78.0% respectively. Confirming the results from the Cutaneous Lymphoma International Consortium (CLIC), LDH and LCT had significant prognostic impact. Unlike earlier studies, stage did not have prognostic impact; we speculate that greater relative benefit favours patients with extensive lymphomatous nodal disease (Stage IVA2) compared to historical reports. For patients ineligible for AlloSCT, the prognosis remains relatively poor (5-year DSS 51.4% and OS 49.6%), representing ongoing unmet needs for more effective novel agents and investigation of improved therapeutic combinations.

Role of extracorporeal photopheresis in the management of acute and chronic graft versus disease: current status.

Extracorporeal photopheresis (ECP) is a therapy that combines the collection of mononuclear cells by apheresis, the addition of a photosensitizer (8-methoxisoralen), the illumination of the product with ultraviolet A light, and the immediate infusion of the product to the patient. Initially developed and approved to treat T-cell cutaneous lymphomas, soon started to be used to treat graft versus host disease (GvHD) developed after allogeneic hematopoietic-cell transplantation. The high response rate of ECP in skin, ocular, oral, pulmonary, and liver forms of chronic GvHD, the steroid-sparing effect, and the improved overall survival of treated patients, made ECP one of the second-line treatments used to treat steroid-resistant acute and chronic GVHD. Recently, the development of new drugs for treating GVHD has changed the position of ECP in the therapy of GVHD and has started to be used in combination with drugs for increasing the response rate to the treatment in severe or resistant forms of acute and chronic GVHD. ECP remains an essential therapeutic resource in the management of patients with refractory acute and chronic GVHD.

On the Way to Curing Advanced-Stage Mycosis Fungoides/Sézary Syndrome

Advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) have poor prognosis with median survivals of less than 5 years. Although a variety of treatments are approved for MF/SS patients, durable complete remissions (CR) are rare. Advanced-stage MF or SS patients who achieved CR and maintained in CR or stage IA for more than 10 years were identified by a retrospective search of the principal investigator's database. Of 2266 patients diagnosed with MF or SS, 23 patients with advanced-stage MF/SS (6 IIB, 1 IIIB, 5 IVA1, 3 IVA2, 8 IVB) who achieved CR and maintained in CR or stage IA for ≥ 10 years were identified. As final/curative treatment, 11 patients underwent allogeneic stem cell transplantation (SCT). Most patients presented at young age, underwent SCT with reduced intensity conditioning regimen, had matched related donors, and controllable post-transplant graft versus host disease. Eleven patients were treated with TSEB as part of combined modality protocol in 2 patients and debulking therapy before allogeneic SCT in 9 patients. Five stage IIB patients achieved CR with radiotherapy. Four patients with blood involvement were treated with extracorporeal photopheresis (ECP) in combination with long-term antibiotics and immunomodulatory agents. Long-term antibiotics were given to 14 patients. TSEB followed by allogeneic SCT, radiotherapy, ECP plus long-term antibiotics and immunomodulatory agents were the most common curative/final treatments found in our patients. We are reporting the details of our long-term complete responders' treatment course in the hopes of obtaining more cure responses in the future.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.