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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 -
Transplantation Jul 2018Lung transplantation is a therapeutic option for select patients with end-stage lung disease. However, successful lung transplantation is hampered by chronic lung... (Review)
Review
BACKGROUND
Lung transplantation is a therapeutic option for select patients with end-stage lung disease. However, successful lung transplantation is hampered by chronic lung allograft dysfunction, in particular bronchiolitis obliterans syndrome (BOS). Although there is no approved or standard treatment for BOS, which may have several distinct phenotypes, extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment.
METHODS
We reviewed all relevant clinical data indexed on PubMed from 1987 to 2017 to evaluate the role of ECP in patients with BOS.
RESULTS
Seven small studies investigated the immunomodulatory effects of ECP in patients after solid organ transplant, and 12 studies reported clinical data specific to ECP therapy for BOS. Studies indicate that ECP triggers an apoptotic cellular cascade that exerts various immunomodulatory effects mediated via increases in anti-inflammatory cytokines, a decrease in proinflammatory cytokines, and an increase in tolerogenic regulatory T cells. Clinical evidence derived from relatively small single-center studies suggests that ECP therapy is associated with improvement or stabilization in lung function and sustainable, statistically significant, decreases in the rate of lung function decline in patients with BOS. Additionally, when adverse event data were reported, ECP was generally well tolerated. None of the comparative studies were randomized.
CONCLUSIONS
Immunomodulation mediated via ECP is a rational therapeutic option that may improve clinical outcomes in patients with BOS, particularly in the context of in-depth patient phenotyping as part of a stratified approach to treatment; good quality randomized controlled trials are needed to confirm observational findings.
Topics: Bronchiolitis Obliterans; Graft Rejection; Humans; Immunomodulation; Lung Diseases; Lung Transplantation; Photopheresis; Treatment Outcome
PubMed: 29557913
DOI: 10.1097/TP.0000000000002168 -
Experimental Hematology & Oncology Feb 2021The aim of the present study was to evaluate the circulating T regulatory cells (Tregs) in patients undergoing extracorporeal photopheresis (ECP) for the prevention of...
The aim of the present study was to evaluate the circulating T regulatory cells (Tregs) in patients undergoing extracorporeal photopheresis (ECP) for the prevention of chronic graft-versus-host disease (GvHD) and to search for any correlation between Tregs counts and chronic GvHD occurrence. Among n = 12 patients with complete longitudinal data, the median cumulative values of absolute peripheral Tregs counts were 21.64 and 63.49 cells/µL for patients who developed chronic GvHD and those who did not develop it, respectively (p = 0.05). The analysis of the median absolute counts of peripheral HLA-DR + Tregs provided similar results, showing that 20% (1 out of 5) and 100% (7 out of 7) of patients with HLA-DR + Tregs values of > 5 cells/µL were in the GvHD and non-GvHD groups, respectively (p = 0.01). In conclusion, the present results support the involvement of Tregs in the prevention of chronic GvHD in patients receiving ECP and suggest Tregs count as a potential biomarker of ECP effectiveness. Future strategies are needed to enhance Tregs expansion and/or activity in conjunction with ECP for an effective chronic GvHD prevention.
PubMed: 33593442
DOI: 10.1186/s40164-021-00210-9 -
Transfusion and Apheresis Science :... Dec 2009Acute and chronic graft versus host disease are frequent and potentially severe complications of allogeneic hematopoietic stem cell transplantation and are among the... (Review)
Review
Acute and chronic graft versus host disease are frequent and potentially severe complications of allogeneic hematopoietic stem cell transplantation and are among the leading causes of non-relapse transplant-related mortality. For patients with steroid refractory disease, prognosis is particularly poor and although a variety of treatment options are available, responses are commonly transient and the side effects often intolerable. Since it was first introduced for the treatment of cutaneous T-cell lymphoma, extracorporeal photo-apheresis has been utilized as an immunomodulatory therapy for certain autoimmune diseases and solid organ transplant rejection. Recently, extracorporeal photo-apheresis has become a promising alternative for patients with graft versus host disease with disabling or potentially lethal complications. Here we review the experience of extracorporeal photo-apheresis for the treatment of steroid refractory acute and chronic graft versus host disease based on the current literature.
Topics: Drug Resistance; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Photopheresis; Steroids
PubMed: 19819186
DOI: 10.1016/j.transci.2009.09.007 -
Dermatology Online Journal Nov 2020A 65-year-old man with acute myeloid leukemia 6 was treated by bone marrow allograft, developed a systemic classic chronic graft versus host disease with hepatic,...
A 65-year-old man with acute myeloid leukemia 6 was treated by bone marrow allograft, developed a systemic classic chronic graft versus host disease with hepatic, rheumatologic, ophthalmic, and muco-cutaneous involvement. He received systemic corticosteroid, ruxolitinib and extracorporeal photopheresis which resulted in complete remission. During follow-up the patient presented with viral cutaneous warts on his neck and submandibular area. After various subsequent topical treatments, he developed localized cutaneous GVHD without any general GVHD reactivation symptoms. To the best of our knowledge, there has been no description in the literature of a graft versus host disease developing after local immunomodulatory or cytotoxic treatments. Topical therapies are commonly used by dermatologists for superficial skin cancers and some viral skin lesions, in high risk populations such as organ transplant patients with regular follow-up.Practitioners should be made aware of a possible localized cutaneous GVHD reactivation induced by Koebner phenomenon after local therapy.
Topics: Adrenal Cortex Hormones; Aged; Allografts; Bone Marrow Transplantation; Chronic Disease; Dermatitis; Graft vs Host Disease; Humans; Iatrogenic Disease; Immunomodulation; Leukemia, Myeloid, Acute; Male; Nitriles; Psoriasis; Pyrazoles; Pyrimidines; Skin Diseases; Warts
PubMed: 33342180
DOI: No ID Found -
American Journal of Hematology Jul 2008Photopheresis, initially established as an effective treatment of cutaneous T-cell lymphoma, has in recent years also been used to treat chronic graft vs. host disease,... (Review)
Review
Photopheresis, initially established as an effective treatment of cutaneous T-cell lymphoma, has in recent years also been used to treat chronic graft vs. host disease, heart transplant rejection, and several other conditions requiring immunosuppression. Despite reported beneficial results of this procedure in treatment of various conditions, randomized controlled clinical trials are lacking for the majority of suggested indications. Furthermore, the mechanisms of action of this procedure are still unclear. Deeper understanding of the molecular basis of photopheresis-based immunomodulation will allow better selection of patients to be treated and will facilitate development of novel, minimally toxic immunomodulatory treatments.
Topics: Animals; Chronic Disease; Graft vs Host Disease; Humans; Immune Tolerance; Lymphoma, T-Cell, Cutaneous; Organ Transplantation; Photopheresis
PubMed: 18335565
DOI: 10.1002/ajh.21166 -
Dermatologic Clinics Jul 2000Dermatologists are frequently involved in the management of cutaneous T-cell lymphoma (CTCL) and graft-versus-host disease (GVHD). The similarities of these two entities... (Review)
Review
Dermatologists are frequently involved in the management of cutaneous T-cell lymphoma (CTCL) and graft-versus-host disease (GVHD). The similarities of these two entities are reviewed in the context of clinical and histologic findings, pathogenesis, and therapy. Photopheresis therapy (extracorporeal photochemotherapy) is used in the treatment of both entities, and the mechanisms underlying the responses represent yet another striking similarity of these two crippling dermatologic diseases.
Topics: Graft vs Host Disease; Humans; Lymphoma, T-Cell, Cutaneous; Photopheresis; Skin Neoplasms
PubMed: 10943537
DOI: 10.1016/s0733-8635(05)70190-x -
The Cochrane Database of Systematic... Sep 2022Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of... (Review)
Review
BACKGROUND
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE (PubMed) and Embase (Ovid) databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
SELECTION CRITERIA
We sought to include randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in children and adolescents with aGvHD after HSCT.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author.
MAIN RESULTS
We identified no additional studies in the 2021 review update, so there are still no studies that meet the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions.
Topics: Adolescent; Adrenal Cortex Hormones; Child; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 36166494
DOI: 10.1002/14651858.CD009759.pub4 -
Hematology, Transfusion and Cell Therapy 2023Although 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...
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.
PubMed: 35165075
DOI: 10.1016/j.htct.2021.08.014 -
PloS One 2016This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer...
This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which in-turn unleashes both short- and potentially long-term antitumor activity of photo-active therapeutics like psoralen.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Transformation, Neoplastic; Dose-Response Relationship, Radiation; Ficusin; Mice; Neoplasms; X-Ray Therapy
PubMed: 27583569
DOI: 10.1371/journal.pone.0162078