Real-world evidence of heparin and citrate use in extracorporeal photopheresis: A hypothesis-generating data review of device settings and performance.

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.

Extracorporeal photopheresis for systemic sclerosis: A meta-analysis of randomized clinical trials.

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

Interventions for mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions. OBJECTIVES: To assess the effects of interventions for MF in all stages of the disease. SEARCH METHODS: We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines. MAIN RESULTS: This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs. AUTHORS' CONCLUSIONS: ​​There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.

75% Complete Response and 15% Partial Response to Extracorporeal Photopheresis Combined With Other Therapies in Resistant Early Stage Cutaneous T-Cell Lymphoma.

INTRODUCTION: Extracorporeal photopheresis (ECP) has been used for the treatment of advanced stage or treatment refractory cutaneous T-cell lymphoma (CTCL) since 1987, and more recently has also been shown to be of benefit for earlier stage resistant CTCL. Complete response rates in prior studies of ECP in early CTCL have ranged from 0% to 40%. METHODS: We reviewed electronic medical records of all CTCL patients seen in the University of Kansas Cancer Center between June 2007 and May 2011. International review board approval was obtained. Inclusion criteria were (1) early stage CTCL and (2) ECP treatment. Data included demographics, type of intravenous access employed, CTCL subtype, cytogenetic features, adverse events, adjuvant treatments, and survival time in years. Treatment response was assessed via a modified severity weighted assessment tool (mSWAT). Primary outcome measures were response rates to ECP at 6 months and 12 months after beginning treatment. RESULTS: Of 20 patients (13 female; 7 male), 7 were Stage 1A, 11 were 1B, and 2 were 2A. Seven patients with stable disease and 2 patients with progression at 6 months received adjuvant therapy (PUVA/systemic retinoids/metotrexate/interferon) in addition to ECP. Twelve-month response to ECP was 90%: 15 patients (75%) had complete responses, 3 (15%) had partial responses, 1 had stable disease, and 1 progressed. CONCLUSION: Used alone or in combination with adjuvant treatments, ECP can be an effective treatment method in early stage CTCL.

J Drugs Dermatol. 2016;15(10):1212-1216.

Fotoféresis en el tratamiento de Síndrome de Sézary: Caso clínico / Sézary syndrome treated with extracorporeal photopheresis: Report of one case

Sézary syndrome (SS) is an unusually aggressive T- cell lymphoma characterized by the triad of erythroderma, the presence of more than 1,000 Sézary cells in peripheral blood and lymphadenopathies. It is accompanied by generalized pruritus and poor quality of life. The management of SS depends on its stage, patient comorbidities, and treatment availability. Extracorporeal photopheresis (ECP) is the first line of treatment for patients with T-cell lymphomas in stage IVA1, IVA2 or SS. This treatment comprises three phases: leukapheresis, photoactivation and subsequent reinfusion of lymphocytes. As it is an immunomodulatory therapy it does not produce generalized immunosuppression. We report a 76 year-old male with SS stage IIIb initially treated with 12 sessions of ultraviolet phototherapy without response. After 10 well-tolerated sessions of ECP, itching and skin lesions eventually disappeared.

Phototherapy, photodynamic therapy and photophoresis in the treatment of connective-tissue diseases: a review.

Connective-tissue disorders, which include lupus erythematosus, morphoea/scleroderma and dermatomyositis, are characterized by cutaneous manifestations that are sometimes resistant to conventional therapy. Light treatments, which include phototherapy, photodynamic therapy (PDT) and photopheresis, are routinely utilized in the treatment of dermatological conditions and may provide unique mechanisms of action in the treatment of these connective-tissue disorders. The objective of this study is to conduct a review of the literature that describes the use of phototherapy, PDT and photopheresis in the treatment of lupus erythematosus, morphoea/scleroderma and dermatomyositis. A MEDLINE search was conducted to find articles that discuss treatment of connective-tissue diseases with light therapies and more than 30 publications that discuss light therapy for these diseases were identified. These range in design from case reports to randomized, prospective trials. Study outcomes and details were summarized and presented within each connective-tissue disease by light therapy modality, which includes phototherapy, PDT and photopheresis. Although there is a known association between photosensitivity and connective-tissue diseases, light therapies, when used appropriately, may be legitimate therapeutic options for recalcitrant cutaneous manifestations in lupus erythematosus, morphoea/scleroderma and dermatomyositis.

[Sézary syndrome treated with extracorporeal photopheresis: Report of one case]. / Fotoféresis en el tratamiento de Síndrome de Sézary: Caso clínico.

Sézary syndrome (SS) is an unusually aggressive T- cell lymphoma characterized by the triad of erythroderma, the presence of more than 1,000 Sézary cells in peripheral blood and lymphadenopathies. It is accompanied by generalized pruritus and poor quality of life. The management of SS depends on its stage, patient comorbidities, and treatment availability. Extracorporeal photopheresis (ECP) is the first line of treatment for patients with T-cell lymphomas in stage IVA1, IVA2 or SS. This treatment comprises three phases: leukapheresis, photoactivation and subsequent reinfusion of lymphocytes. As it is an immunomodulatory therapy it does not produce generalized immunosuppression. We report a 76 year-old male with SS stage IIIb initially treated with 12 sessions of ultraviolet phototherapy without response. After 10 well-tolerated sessions of ECP, itching and skin lesions eventually disappeared.

Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions.

Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination--including immunomodulators and histone-deacetylase inhibitors--are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS.

Topical therapies for oral lichen planus management and their efficacy: a narrative review.

Oral Lichen Planus (OLP) is a chronic inflammatory condition implicating T cell-mediated cytotoxicity, and involving oral mucosal surfaces. Several therapeutic regimens have been evaluated to treat OLP and pain related, but often without high level of evidence. Topical formulations are the favourite for the majority of cases; bioadhesive formulations have been considered very useful and practical for local drug delivery in oral mucosa, due to the increased residence time on the oral mucosa of the dosage forms and better therapeutic efficacy. In this narrative review, authors try to illustrate the current topical managements for OLP from the accessible literature on this topic. Steroids are very helpful in discomfort and making better quality of life: they are considered the first-line treatment even if they could cause secondary candidosis, and sometimes bad taste, nausea, dry mouth, sore throat or swollen mouth. Other substances or devices by topical administration are adopted especially when the first line approach is refractory. This is the case when retinol with its synthetic and natural analogues (retinoids), hyaluronic acid, or Aloe Vera are chosen. Recent topical applications for OLP therapy include phototherapy and low/high energy pulsing light; the treatment with extracorporeal photochemotherapy is also reasonable and promising. Finally, calcineurin inhibitors (i.e. cyclosporine, tacrolimus and pimecrolimus), antioxidant and biologics (i.e alefacept, efalizumab, basiliximab, TNF-α inhibitors - infliximab, rituximab) may be alternative approaches when OLP does not respond to the standard protocols. In this scenario, there are several studies on molecules different from glucocorticosteroids, but not sufficient or statistically adequate to justify their evidence-based use in OLP; large randomized placebo controlled trials are required to evaluate the safety and effectiveness of these non conventional therapies. In conclusion, since OLP is a chronic disease and requires long-term management, the dental/medical practitioner, who treats OLP patients, needs to know the natural history of OLP, how to monitor, and how to treat, taking in account all of the available modalities conventional and not, with pros and cons.

UV treatment of chronic skin graft-versus-host disease--focus on UVA1 and extracorporeal photopheresis.

Chronic graft-versus-host disease (GVHD) is a serious and life-threatening complication after allogeneic hematopoietic stem cell transplantation. Cutaneous manifestations such as lichenoid or sclerotictype skin changes have been frequently observed in these patients. UVA1 phototherapy appears as a very effective treatment option for treatment-refractory lichenoid and sclerodermatous GVHD. Substantial improvements can often be achieved within 8-12 weeks of treatment allowing for subsequent reduction or withdrawal of immunosuppressive medications. UVA1 treatment acts via a local effect and is therefore only indicated for cutaneous manifestations of GVHD. In patients with multiorgan involvement by chronic GVHD, extracorporeal photopheresis is an efficacious and safe secondline therapy for steroid-refractory disease in both pediatric as well as adult patients. Besides high response rates in cutaneous and extracutaneous manifestations of chronic GVHD, a substantial corticosteroid-sparing effect and improved survival rates have been reported in patients given extracorporeal photopheresis treatment.

Donor lymphocyte infusions combined with systemic PUVA/bexarotene as an effective bimodal immunologic approach in a patient with relapsed cutaneous T cell lymphoma after allogeneic stem cell transplantation.

One central challenge of allogeneic stem cell transplantation is the positive correlation between graft versus lymphoma effect (GvL) and graft-versus-host disease (GvHD). To date, specific targeting of GvL antigens with effector T cells and of GvHD antigens with specific regulatory T cells remains the subject of experimental research. In clinical reality, negative modulation of GvHD, e.g. by immunosuppression, reduces GvL and positive modulation of GvL, e.g. by donor lymphocyte infusions, often amplifies GvHD. Clinically feasible strategies to induce GvL while simultaneously reducing GvHD are urgently needed. Here, we report the case of an early relapsed primary cutaneous T cell lymphoma in tumor stage after allogeneic stem cell transplantation which was successfully treated with a parallel administration of donor lymphocyte infusions (DLI) and systemic PUVA and bexarotene which led to sustained complete remission without onset of acute GvHD. After termination of the treatment with PUVA/bexarotene subacute chronic GvHD occurred but was subsequently brought under control by extracorporeal photopheresis. We suggest that the combination of DLI and PUVA/bexarotene might be an interesting immunologic bimodal treatment option which warrants further investigation.

Experimental study of the effects of low-intensity monochromatic photodiode radiation and antitumor efficiency of cyclophosphamide injected with autoblood.

Experimental study of extracorporeal exposure of autoblood to red monochromatic photodiode radiation for improving antitumor efficiency of cyclophosphamide injected with autoblood was carried out on the model of sarcoma 45 cells ectopically transplanted to the lungs. Co-incubation of irradiated autoblood with cyclophosphamide and reinfusion of the blood to animals increased the antitumor efficiency of chemotherapy in animals with tumors.

The mechanisms of action of phototherapy in the treatment of the most common dermatoses.

Phototherapy denotes the use of ultraviolet (UV) light in the management of several dermatoses. Most phototherapy regimens utilize ultraviolet radiation of different wavelenghts. Currently, irradiations with broadband UVB (290-320 nm), narrowband UVB (311-313 nm), 308 nm excimer laser, UVA 1 (340-400 nm), UVA with psoralen (PUVA), and extracorporeal photochemotherapy (photopheresis) are being used. The interplay of the various photobiologic pathways is far from being completely understood. Disordes that may benefit from such approach are numerous, with psoriasis, atopic dermatitis, cutaneous T-cell lymphomas, morphea, and vitiligo as main indications. The immunomodulatory effects of UVB radiation primarily affect the epidermis and superficial dermis, while UVA radiation affects mid and deep dermal components, especially blood vessels. UVB radiation is absorbed by endogenous chromophores, such as nuclear DNA, which initiates a cascade of events. Absorption of UV light by nucleotides causes the formation of DNA photoproducts and suppresses DNA synthesis. In addition UV light stimulates synthesis of prostaglandins and cytokines that play important roles in immune suppression. It may reduce the number of Langerhans cells, cutaneous T lymphocytes and mast cells in the dermis. UV radiation can also affect extranuclear molecular targets located in the cytoplasm and cell membrane. Immune suppression, alteration in cytokine expression, and cell cycle arrest may all contribute to the suppression of disease activity. PUVA is a form of chemophototherapy which uses UVA light to activate chemicals known as psoralens, hence psoralen ultraviolet A. The conjunction of psoralens with epidermal DNA inhibits DNA replication and causes cell cycle arrest. Psoralen photosensitization also causes an alteration in the expression of cytokines and cytokine receptors. Psoralens interact with RNA, proteins and other cellular components and indirectly modify proteins and lipids via singlet oxygen-mediated reactions or by generating of free radicals. Infiltrating lymphocytes are strongly suppressed by PUVA, with variable effects on different T-cell subsets. Psoralens and UV radiation also stimulate melanogenesis. Extracorporeal photopheresis is technique used in treatment of erythrodermic cutaneous lymphomas. It is very potent in induction of lymphocyte apoptosis. Despite the introduction of numerous effective systemic medications and biologic agents in dermatology, phototherapy remains a reliable, and often preferred option for several dermatoses.

Photochemotherapy induces the apoptosis of monocytes without impairing their function.

BACKGROUND: Extracorporeal photopheresis (ECP) is a powerful therapy currently used to treat various hematological disorders as in graft versus host disease. Clinical data clearly demonstrate its efficacy and immunomodulation toward the pathogenic T cells. However, ECP mechanism of action is still poorly understood. Monocytes represent up to 30% of the total amount of treated cells and are known to play an important role in adaptive immunity. However, data from previous reports analyzing the effect of psoralen and UV-A irradiation (PUVA) on their functions are heterogeneous. In this study, we focused on the effect of PUVA on human monocytes functions in adaptive immunity. DESIGN AND METHODS: Purified human monocytes were treated in vitro by PUVA. We measured their kinetic of apoptosis after the treatment. We also determine whether their phenotype and functionalities were modified. Finally, we assessed the functionalities of PUVA-treated monocytes-derived dendritic cells (DC). RESULTS: PUVA treatment sentenced purified monocytes to die in 6 days and immediately altered their migratory capacities without impairing their ability of endocytosis. It also up-regulated co-stimulatory molecules and production of inflammatory cytokines on activation and consequently stimulated allogeneic or autologous T cells as efficiently as untreated monocytes. Moreover, PUVA-treated monocytes retained their ability to differentiate into fully functional DC that maturated and stimulated T cells as well as normal DC. CONCLUSIONS: Our data demonstrate that monocytes undergo apoptosis and loose a part of their migratory capacity after ECP and the surviving cell functionalities are not impaired, suggesting that monocytes have a minor effect on ECP-mediated immunomodulation.

Combination therapy with extracorporeal photopheresis, interferon-alpha, PUVA and topical corticosteroids in the management of Sézary syndrome.

BACKGROUND: Extracorporeal photopheresis (ECP) is recommended for the treatment of Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL). Several combination therapies are used to increase response rates to ECP. PATIENTS AND METHODS: We report our experience with the combination therapy of ECP, interferon-alpha, PUVA and topical corticosteroids in SS. RESULTS: The treatment outcome in 12 SS patients was retrospectively analyzed and showed an overall response rate to this combination treatment of 42 % with 4/12 patients achieving a partial remission and 1/12 patients a stable disease. The median overall survival time was 42 months. We investigated several clinical and laboratory parameters as an indicator for a response to treatment in our patient cohort. A combined analysis of the erythroderma assessment scale, WBC, LDH, CD4/CD8 ratio and the number of Sézary cells revealed that a reduction of several parameters significantly correlated with response to treatment. The parameters which correlated best with response were number of Sézary cells, CD4/CD8 ratio and WBC. CONCLUSIONS: The investigated combination therapy was effective and well-tolerated in a subgroup of SS patients but needs to be evaluated in a larger patient population.

Fotoféresis / Photopheresis

No disponible

No disponible

Fotoféresis extracorpórea en Dermatología / Extracorporeal Photopheresis in Dermatology

La fotoquimioterapia extracorpórea o fotoféresis es una terapia inmunomoduladora que combina la leucoféresis con la fototerapia. Después de la separación de un plasma rico en leucocitos, se administra ex vivo un fotosensibilizante junto con radiación ultravioleta A y posteriormente se reinfunde en el paciente. El mecanismo de acción exacto de la fotoféresis no se conoce completamente, aunque se piensa que la inducción de apoptosis de linfocitos y la formación de células dendríticas desempeña un papel fundamental en el desarrollo de una respuesta inmunológica contra las células patógenas. Esta terapia se utilizó inicialmente para el tratamiento del linfoma cutáneo de células T. Desde entonces, basándose en su eficacia y seguridad, se ha empleado en múltiples patologías tanto cutáneas como no cutáneas, con resultados variables. Los distintos centros han utilizado diferentes criterios de selección de pacientes, pautas de tratamiento y protocolos de monitorización, lo que podría contribuir a la diferencia de resultados (AU)

Extracorporeal photochemotherapy or photopheresis is an immunomodulatory therapy that combines leukapheresis with phototherapy. Blood from the patient is processed to give a leukocyte-rich plasma, which is then treated ex vivo with a photosensitizer and ultraviolet A radiation before reinfusion back into the patient. The exact mechanism of action of photopheresis has not been fully elucidated although it is thought that induction of leukocyte apoptosis and formation of dendritic cells is essential for the development of an immune response to pathogenic cells. Extracorporeal photophoresis was initially used for treating cutaneous T-cell lymphoma. Since then, in view of its efficacy and safety, it has been used in a number of cutaneous and noncutaneous diseases with uneven results, which can in part be explained by the different patient selection criteria, therapy regimens, and follow-up protocols used in different hospitals (AU)

Cutaneous T cell lymphoma: translating immunobiology into therapeutic opportunities.

Cutaneous T cell lymphoma (CTCL) has always served as a proving ground where conceptual advances in immunology can be tested and the results translated into clinical practice. From the earliest studies that used sheep red blood cells to identify the malignant cell as a T lymphocyte to molecular demonstration of the clonalilty of the disease, basic science techniques have provided sign posts that allow us to understand the clinical features seen in the patients. We continue to apply this paradigm to develop new insights into the role of the immune system in CTCL with the goal of using this knowledge to enhance the therapeutic options available to the patient. This article will review the studies that have led to our current understanding of the immunobiology of CTCL and the new therapeutic approaches that are being tested in this disease.

Extracorporeal photopheresis as a treatment for patients with severe, refractory atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a complex disease with a variety of possible treatment regimens. The study objective was to demonstrate that methoxsalen used in conjunction with the Uvar XTS photopheresis system (Therakos, Exton, Pa., USA) is safe and can have a clinical effect on the skin manifestations and the quality of life in patients with severe, refractory AD. METHODS: Single-arm, open-label treatment using the Uvar XTS photopheresis system. Seven patients (4 male and 3 female, median age: 47 years) with severe (SCORAD >45) AD of at least 12 months duration who in the preceding 12 months had been refractory to all 3 of the first-line therapies for AD, i.e. topical steroids, topical calcineurin inhibitors and one form of phototherapy (UVA, UVB or PUVA), or to one of the second-line therapies like systemic steroids or cyclosporine were included in the study. Treatment consisted of two extracorporeal photopheresis treatments (ExP) on successive days every 2 weeks for a minimum of 12 weeks to a maximum of 20 weeks. Quality of life assessment was performed with the SF-36 Health Survey and the Functional Assessment of Chronic Illness Therapy FACT-G Survey. Clinical improvement was documented with SCORAD assessment. RESULTS: ExP led to a significant decrease in the SCORAD score from 77.7 after 10 cycles to 55.6. Patients reported that they had begun to notice improvement of their skin conditions after 5 cycles of photopheresis. The FACT-G score showed significant improvement from 64.8 to 72.9 (p < 0.05) and the SF-36 Health Survey showed significant improvement in the emotional well-being subscores (p < 0.05). CONCLUSIONS: ExP can have a significant therapeutic effect on the skin and quality of life improvement in a selected group of patients with severe AD who are refractory to conventional forms of therapy. However, larger studies are needed to further evaluate its therapeutic potential.

Assessing the potential role of photopheresis in hematopoietic stem cell transplant.

The First International Symposium on Photopheresis in Hematopoietic Stem Cell Transplantation was held in Vienna, Austria with an educational grant from Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed: (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune tolerance and the immunology of phototherapy and (3) current standard treatment and prevention strategies of acute and chronic GvHD and the use of extracorporeal photopheresis (ECP). The objectives of the meeting were to open a dialogue among leading researchers in photobiology, immunology, and hematopoietic stem cell transplantation; foster discussions and suggestions for future studies of the mechanism of action of ECP in acute and chronic GvHD; and promote collaboration between basic scientists and clinicians. As can be seen from the summaries of the individual presentations, important advances have been made in our understanding of GvHD, including the use of photoimmunology interventions and the development of robust model systems. It is our expectation that data from photoimmunology studies can be used to generate hypotheses in animal models that can further define the mechanism of action of ECP and help translate the findings to clinical trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.