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PubMed1998

Photopheresis for the prevention of rejection in cardiac transplantation. Photopheresis Transplantation Study Group.

BACKGROUND: Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the safety and efficacy of photopheresis in the prevention of acute rejection of cardiac allografts. METHODS: A total of 60 consecutive eligible recipients of primary cardiac transplants were randomly assigned to standard triple-drug immunosuppressive therapy (cyclosporine, azathioprine, and prednisone) alone or in conjunction with photopheresis. The photopheresis group received a total of 24 photopheresis treatments, each pair of treatments given on two consecutive days, during the first six months after transplantation. The regimen for maintenance immunosuppression, the definition and treatment of rejection episodes, the use of prophylactic antibiotics, and the schedule for cardiac biopsies were standardized among all 12 study centers. All the cardiac-biopsy samples were graded in a blinded manner at a central pathology laboratory. Plasma from the subgroup of 34 patients (57 percent) who were enrolled at the nine U.S. centers was analyzed by polymerase-chain-reaction amplification for cytomegalovirus DNA. RESULTS: After six months of follow-up, the mean (+/-SD) number of episodes of acute rejection per patient was 1.44+/-1.0 in the standard-therapy group, as compared with 0.91+/-1.0 in the photopheresis group (P=0.04). Significantly more patients in the photopheresis group had one rejection episode or none (27 of 33) than in the standard-therapy group (14 of 27), and significantly fewer patients in the photopheresis group had two or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27, P=0.02). There was no significant difference in the time to a first episode of rejection, the incidence of rejection associated with hemodynamic compromise, or survival at 6 and 12 months. Although there were no significant differences in the rates or types of infection, cytomegalovirus DNA was detected significantly less frequently in the photopheresis group than in the standard-therapy group (P=0.04). CONCLUSIONS: In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection.

Combined Modality Therapy↗
PubMed2002

Lymphocytes treated by extracorporeal photopheresis demonstrate a drop in the Bcl-2/Bax ratio: a possible mechanism involved in extracorporeal-photopheresis-induced apoptosis.

BACKGROUND: Recently, apoptosis has been identified in treated lymphocytes, prior to their re-infusion, when tested ex vivo. Previous work has demonstrated a close association between the genes p53, Bcl-2 and Bax and apoptosis induced by UV irradiation. OBJECTIVES: We wanted to establish whether the expression of the protein product of these genes was altered in lymphocytes treated with extracorporeal photopheresis (ECP) prior to re-infusion and therefore possibly implicated in the early apoptosis observed. METHOD: Lymphocytes were isolated immediately before treatment and immediately prior to re-infusion and tested for intracellular levels of p53, Bcl-2 and Bax proteins. RESULTS: No increase in p53 expression was observed at re-infusion; however, the mean fluorescent intensity ratio of the apoptotic inhibitor protein Bcl-2 to the apoptosis-inducing protein Bax dropped significantly. CONCLUSION: The early apoptosis observed in ECP-treated lymphocytes at re-infusion might be attributed to dysregulation in the expression of the apoptotic genes Bcl-2 and Bax.

Apoptosis↗
PubMed1999

Adjuvant treatment of refractory lung transplant rejection with extracorporeal photopheresis.

BACKGROUND: Extracorporeal photopheresis is an immunomodulatory technique in which a patient's leukocytes are exposed to ultraviolet-A light after pretreatment with 8-methoxypsoralen (methoxsalen). There have been few reports describing the use of extracorporeal photopheresis in lung transplant recipients. METHODS: We reviewed our experience using extracorporeal photopheresis in 8 lung transplant recipients since 1992. All 8 patients had progressively decreasing graft function and 7 were in bronchiolitis obliterans syndrome grade 3 before the initiation of photopheresis. One patient had undergone a second transplant operation for obliterative bronchiolitis. Two patients had a pretransplantation diagnosis of chronic obstructive pulmonary disease, 1 alpha1-antitrypsin deficiency, 1 cystic fibrosis, 1 bronchiectasis, 1 idiopathic pulmonary fibrosis, and 2 primary pulmonary hypertension. Before refractory rejection developed, all patients had been treated with 3-drug immunosuppression and anti-T-cell therapy. The median time from transplantation to the start of extracorporeal photopheresis was 16.5 months and the median number of treatments was 6. RESULTS: The condition of 5 of 8 patients subjectively improved after extracorporeal photopheresis therapy. In these 5 patients photopheresis was associated with stabilization of the forced expiratory volume in 1 second. In 2 patients there was histologic reversal of rejection after photopheresis. With a median follow-up of 36 months, 7 patients are alive and well. Three patients required retransplantation at a median of 21 months after completion of the treatments. Four patients have remained in stable condition after photopheresis. There were no complications related to extracorporeal photopheresis. CONCLUSION: We believe that this treatment is a safe option for patients with refractory lung allograft rejection when increased immunosuppression is contraindicated or ineffective.

Adolescent↗
PubMed2003

Photopheresis. Therapeutic potential in preventing restenosis after percutaneous transluminal coronary angioplasty.

Photopheresis (extracorporeal photochemotherapy) is an immunomodulatory therapy that entails the reinfusion of peripheral blood mononuclear cells after exposure to the photoreactive agent methoxsalen and ultraviolet A (UVA) radiation. Currently available at approximately 150 treatment centers worldwide, photopheresis is approved by the US FDA for advanced-stage cutaneous T-cell lymphoma (CTCL) and has also shown promise in treating nonmalignant immune-related conditions such as organ transplant rejection, acute and chronic graft-versus-host disease, and autoimmune disorders. The precise mechanism by which photopheresis evokes clinical responses is unknown, although this modality seems capable of modulating T-cell and monocyte activity. Clinical and laboratory findings suggest that the reinfusion of peripheral blood mononuclear cells after exposure to UVA-activated methoxsalen engenders an immune response against proliferating T-cell clones. Methoxsalen is a naturally occurring furocoumarin that is biologically inert until exposed to UVA radiation at the proper wavelength, at which time it irreversibly cross-links DNA thymine bases and arrests cell proliferation. T cells isolated from the peripheral blood of patients after photopheresis demonstrate significantly increased levels of apoptosis, whereas macrophages and dendritic cells exhibit the ability to phagocytize the apoptotic T cells. It is surmised that photopheresis enhances the uptake, processing, and presentation of distinctive antigens from apoptotic pathogenic T cells by macrophages and dendritic cells leading to the induction of an anticlonotypic response by cytotoxic T cells. Induction by photopheresis of apparently opposite immune processes (i.e. upregulation of an antitumor response and downregulation of allogeneic or autoimmune responses) can be explained by its ability to target either a single malignant T-cell clone (as in CTCL) or multiple activated T-cell clones (as in organ transplant rejection, graft-versus-host disease, or autoimmune disease). Because acute inflammation and T-cell activation may be important in the pathogenesis of restenosis following percutaneous transluminal coronary angioplasty (PTCA), photopheresis was used for the first time at our center to prevent restenosis. A total of 78 patients with single-vessel coronary artery disease amenable to PTCA with or without stent deployment were enrolled, 41 in the control group and 37 in the photopheresis group. Clinical restenosis occurred in significantly less photopheresis patients than control patients (8 vs 27%; p = 0.04), with a relative risk of 0.30 (95% confidence interval, 0.09-1.00). A multicenter clinical trial following a US FDA-recommended protocol is currently underway to better determine what, if any, impact photopheresis has in preventing restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2001

Identification of clonal T cells in the blood of patients with systemic sclerosis: positive correlation with response to photopheresis.

OBJECTIVES: To search for circulating clonal T-cell populations in patients with systemic sclerosis (SSc), and to determine whether T-cell clonality in the blood predicts therapeutic response to photopheresis. DESIGN: Analysis of clonal T-cell receptor gamma gene rearrangements before photopheresis treatment and blinded clinical evaluation of cutaneous response to photopheresis in a case series. SETTING: University hospital setting. PATIENTS: Thirteen consecutive patients with SSc. INTERVENTIONS: Photopheresis in 11 patients. MAIN OUTCOME MEASURES: Clonality of T cells in the blood before photopheresis and clinical response to photopheresis. RESULTS: Screening of blood samples from 13 SSc patients for clonal T-cell receptor gamma gene rearrangements revealed a monoclonal T cell population in 6 (46%) of 13 SSc patients. Clinical response to photopheresis in 11 patients was evaluated in a blinded manner using skin severity scores. Clonality of T cells appeared to be associated with a higher chance of response to photopheresis therapy, as 4 (67%) of 6 patients in the clone-positive group vs 1 (20%) of 5 in the clone-negative group experienced a clinically significant response to treatment. CONCLUSIONS: A high proportion of patients with SSc have detectable expanded clonal T-cell populations in the peripheral blood, and such patients appear more likely to respond to photopheresis.

Adult↗
PubMed1996

Treatment of cutaneous T-cell lymphoma with extracorporeal photopheresis monotherapy and in combination with recombinant interferon alfa: a 10-year experience at a single institution.

BACKGROUND: Extracorporeal photopheresis is a pheresis-based therapy that permits the direct targeting of psoralen-mediated photochemotherapy to circulating pathogenic T cells. Although photopheresis is currently used to treat cutaneous T-cell lymphoma (CTCL), limited data are available regarding overall response rates and durability of responses among patients with advanced disease. Furthermore, little is known about the effectiveness and tolerability of combined regimens employing other biologic response modifiers including interferon alfa. OBJECTIVE: Our purpose was to determine the efficacy of photopheresis among 41 patients with the clinical and laboratory diagnosis of CTCL; the majority of patients had stage III or IV disease with the presence of circulating malignant T cells. METHODS: A retrospective chart review during a 10-year period at a single university hospital was performed for all patients receiving either photopheresis monotherapy on two consecutive days every 4 weeks (one cycle) and for an additional 12 patients who also received interferon alfa 1.5 to 5 million U subcutaneously three to five times weekly. RESULTS: Thirty-one of 41 patients (76%) were treated for six or more cycles. The remaining 10 were treated with less than six cycles because of rapidly progressing disease (n = 6), death unrelated to CTCL (n = 2), or withdrawal from treatment (n = 1); one of the 10 patients had only received five cycles of treatment but is still receiving therapy. Twenty-eight of the 31 patients treated for six or more cycles received photopheresis alone. Among the 28, seven patients (25%) had a complete remission, 13 (46%) had a partial remission defined as more than 50% clearing of skin disease, and eight (29%) did not respond to treatment. The presence of Sézary cells in the peripheral blood was associated with a favorable response. Median time to treatment failure was 18 months, whereas median survival from initiation of therapy was 77 months and from the time of diagnosis exceeded 100 months. Nine of these 28 patients went on to receive combination therapy with interferon alfa and, in some cases, other agents. Among these nine patients, five had an enhanced clinical response to the combination therapy compared with treatment with photopheresis monotherapy. The combined regimen was well tolerated. CONCLUSION: These results indicate that patients with advanced CTCL can achieve a high response rate for an extended period with photopheresis and that interferon alfa combined with photopheresis is a well-tolerated regimen that appears to produce higher response rates than photopheresis alone.

Adult↗
PubMed1992

Successful treatment of heart transplant rejection with photopheresis.

Photopheresis is a potential therapy for rejection in which reinfusion of mononuclear cells exposed to ultraviolet-A light ex vivo, after treatment with 8-methoxypsoralen in vivo, initiates host immune responses that specifically inhibit the cytotoxicity of the photomodulated mononuclear cells. Between May 1990 and January 1991, 7 heart transplant (HT) patients (age 42.2 +/- 16.7 [mean +/- SD] years) on triple immunosuppression (cyclosporine, corticosteroids, and azathioprine) had 9 episodes of non-hemodynamically compromising moderate rejection that were treated with photopheresis. These episodes of rejection occurred at an average of 114.4 +/- 180.5 (range 8-575) days after HT. After oral administration the mean serum level of 8-methoxypsoralen achieved was 129.0 +/- 72.4 ng/ml. An average of 10.4 +/- 9.6 x 10(9) mononuclear cells were treated with each photopheresis procedure. Photopheresis was performed twice when less than 5 x 10(9) mononuclear cells had been treated with the first procedure. Of 9 rejection episodes treated with photopheresis, 5 required 1 procedure and 4 required 2 procedures. Photopheresis was used to treat a single episode of rejection in 5 pts. and 2 separate rejection episodes in 2 additional pts. Eight of 9 episodes of rejection were successfully reversed by photopheresis as assessed by endomyocardial biopsy (EMB) performed 7 days after treatment. Immunohistochemical analysis of EMB samples revealed that postphotopheresis cell counts for T cells, B cells, and macrophages were reduced compared to pretreatment values and correlated with the histopathologic resolution of rejection. Hemodynamics were normal prephotopheresis and remained unchanged at the time when the postphotopheresis EMB showed no evidence rejection No adverse effects have been observed with photopheresis. Over a follow-up period of 5.3 +/- 4.0 months, rejection and infection rates/pt./follow-up months were 0.3 +/- 0.4 and 0.04 +/- 0.07, respectively. The preliminary, short term results of this pilot study indicate that photopheresis may be efficacious in the treatment of moderate rejection in hemodynamically stable HT patients and thus may be an alternative to corticosteroid pulses.

Adult↗
PubMed1992

Photopheresis versus corticosteroids in the therapy of heart transplant rejection. Preliminary clinical report.

BACKGROUND: Photopheresis is a technique in which reinfusion of mononuclear cells exposed to UV-A light ex vivo after in vivo treatment with 8-methoxypsoralen initiates host-immunosuppressive responses. METHODS AND RESULTS: To determine if photopheresis safely reverses International Society for Heart and Lung Transplantation (ISHLT) rejection grades 2, 3A, and 3B without hemodynamic compromise, 16 heart transplant patients with ISHLT rejection grades 2, 3A, and 3B were randomized to photopheresis or corticosteroid therapy. The average number of mononuclear cells treated with each photopheresis procedure was 9.8 +/- 9.1 x 10(9) (mean +/- SD). Photopheresis and corticosteroids reversed eight of nine and seven of seven episodes of rejection, respectively. The median time from initiation of treatment to rejection reversal was 25 days (range, 6-67 days) in the photopheresis group and 17 days (range, 8-33 days) in the corticosteroid group. Hemodynamics were normal before either treatment and did not change after reversal of rejection. No adverse reactions occurred with photopheresis, and all patients in either treatment group are alive. CONCLUSIONS: These preliminary, short-term results in prospectively randomized patients indicate that photopheresis may be as effective as corticosteroids for treating ISHLT rejection grades 2, 3A, and 3B. The apparently low toxicity and potential efficacy of photopheresis warrant further analysis of its role in the prevention and treatment of heart transplant rejection.

Adult↗
PubMed1996

Chlorpromazine, a candidate drug for photopheresis.

Photopheresis is a therapy for several T-cell-mediated disorders, aiming at a specific immune response against the pathogenic clone of T cells involved. With photopheresis, a mixture of patients' buffy coat and plasma, which contains 8-methoxypsoralen (8-MOP), is diluted with saline and exposed to ultraviolet A radiation (UVA). After the irradiation the treated fraction is reinfused. To improve this therapy and to broaden its scope, insight into the underlying mechanism is essential. Regarding the mechanism, photomodification of biomacromolecules is considered to be crucial in photopheresis. Up to the present, much emphasis has been put on the photobinding to DNA. However, photobinding to proteins can also play an important role in photopheresis, because much of the communication between the various parts of the immune system occurs via protein-protein interactions. In this study we compared the activity of 8-MOP and chlorpromazine (CPZ) in our animal model for photopheresis based on contact hypersensitivity. It proved that CPZ was able to induce specific immune suppression, just as 8-MOP. In addition, photobinding of CPZ and 8-MOP to lymphocytes was determined. It was shown that under conditions relevant for photopheresis the photobinding to DNA of 8-MOP exceeds that of CPZ by a factor of 22. This holds for both rat and human lymphocytes. With the photobinding to proteins it is just the other way round; the photobinding of CPZ exceeded that of 8-MOP by a factor of 23 for rat lymphocytes and 28 for human lymphocytes. This study proves that CPZ is an interesting candidate drug for photopheresis and shows that not only photobinding to DNA is crucial in photopheresis, but photobinding to proteins is important as well.

Adoptive Transfer↗
PubMed1997

Photopheresis treatment enhances CD95 (fas) expression in circulating lymphocytes of patients with systemic sclerosis and induces apoptosis.

We investigated the effects of photopheresis in systemic sclerosis by analysing its influence on lymphocytes with regard to apoptosis and expression of bcl-2 and fas. Peripheral blood lymphocytes isolated immediately before and 24 h after photopheresis were investigated for apoptosis, bcl-2 and fas expression by fluorocytometry, and compared to controls. In addition, leucocytes from systemic sclerosis patients taken directly from the photopheresis system were tested for apoptosis after 24 h in culture. fas expression was similar in controls and patients with systemic sclerosis just before photopheresis, but increased 24 h after photopheresis, mainly due to an increase of CD4+CD95+ cells. bcl-2 was overexpressed in scleroderma peripheral lymphocytes, but not influenced by photopheresis. As compared to healthy controls, the percentage of apoptotic cells 24 h after photopheresis was high in cultured lymphocytes, but not ex vivo. The significant increase in fas on peripheral lymphocytes observed in this study may be a major operative mechanism of photopheresis in addition to (and possibly related to) the induction of apoptosis.

Adult↗
PubMed2006

A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis.

BACKGROUND: Systemic sclerosis is a multisystemic connective tissue disease with marked involvement of the skin and joints for which few effective evidence based therapies are available. To further investigate the efficacy of extracorporeal photochemotherapy on early aggressive cutaneous disease, a randomized, double-blind, placebo-controlled trial was performed. OBJECTIVE: Our aim was to evaluate the efficacy of photopheresis in the treatment of patients with systemic sclerosis (scleroderma). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted at 16 investigational sites in the United States, Canada, and Europe. Sixty-four patients with typical clinical and histologic findings of scleroderma, of less than 2 years' duration, were studied. Patients did not receive any other concomitant treatment for scleroderma. Patients were randomized to receive either active or sham photopheresis treatment on two consecutive days monthly for 12 months. Severity of skin (skin scores assessed in 22 body regions) and joint involvement (60 joints examined for contractures) were assessed on a monthly basis. RESULTS: A statistically significant improvement in skin scores as compared with baseline was observed at 6 months (P = .0024) and 12 months (P = .008) among those who received active photopheresis, but not among those who received sham photopheresis. Comparison of skin scores between the two study arms did not achieve statistical significance because of the small sample size of the study arms. Joint involvement was also significantly improved after 6 months (P = .002) and 12 months (P = .001) of active photopheresis when compared with baseline. LIMITATIONS: The study lacks sufficient statistical power to reveal a significant difference in skin and joint manifestations between the active and sham photopheresis arms. CONCLUSION: Photopheresis induced significant improvement of skin and joint involvement in patients with scleroderma of recent onset; however, any effect when compared with sham treatment and a possible placebo effect may be modest.

Adult↗
PubMed1994

Review of immunomodulation by photopheresis: treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection.

Photopheresis is an apheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon-alpha, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens has also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of tumor necrosis factor alpha (TNF-alpha), and perhaps, to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could benefically affect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection. Randomized, controlled trials for these new indications for photopheresis therapy are currently in the early stages of implementation.

Animals↗
PubMed2004

Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes.

In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4+ CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4(CD29+) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.

Adolescent↗
PubMed2005

The immunological effect of photopheresis in children with newly diagnosed type 1 diabetes.

Photopheresis has been claimed to have immune-modulating effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1- and Th2-like cytokines. Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-gamma and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-gamma, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2-like shift. Thus, the ratio of IFN-gamma/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD65 was reduced after treatment in the photopheresis group. The IFN-gamma/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation.

Adolescent↗
PubMed1990

Extracorporeal photopheresis in psoriasis vulgaris: clinical and immunologic observations.

Four patients with chronic refractory plaque-type psoriasis without arthropathy were treated with extracorporeal photopheresis every other week for 6 to 13 months. In patients 1 and 2, methotrexate was administered concomitantly during the initial part of the trial; the dose was gradually tapered and the drug was discontinued by 6 months. Both patients improved to 23% and 62% of baseline values for percentage of body surface involvement, but their disease then flared when maintenance extracorporeal photopheresis was used alone. Substantial improvement again occurred when lower doses of methotrexate were administered with extracorporeal photopheresis. Patients 3 and 4 were treated initially with extracorporeal photopheresis alone and both improved to 50% and 52% of baseline body surface involvement, respectively, after 4 months of treatment. However, their disease flared because of factors unrelated to treatment. Extracorporeal photopheresis was well tolerated by all patients without evidence of overt toxicity. However, prolonged treatment with extracorporeal photopheresis/methotrexate was accompanied by a decrease in skin reactivity to recall antigens and by decreased capacity of lymphocytes to produce interleukin 2 in response to polyclonal stimuli in vitro. These findings indicate that alternate-week extracorporeal photopheresis has a definite but incomplete suppressive effect on psoriasis vulgaris that may be mediated through an effect on lymphokine production by photomodified cells and that the therapeutic effect of extracorporeal photopheresis may be enhanced by concomitant administration of low doses of methotrexate.

Adolescent↗
PubMed1991

[The application of photopheresis in the therapy of cancerous and autoimmune diseases].

Photopheresis is an extracorporeal form of immunotherapy, recently approved by the FDA for the treatment of cutaneous T-cell lymphoma. During photopheresis lymphocytes are collected from the patients by leukapheresis and after exposure to psoralens and UVA reinfused to the host. The reinfused cells induce an immunological reaction against the neoplastic cells that seems to be clone specific. 37 CTCL patients have been initially treated; 1/4 showed a complete remission, 1/4 did not answer to the therapy and 1/2 showed a clinical improvement without complete remission. The best responders were patients in erythrodermic stage, particularly when photopheresis had been started early. The association with methotrexate induced a complete clinical remission in the cases with a partial answer to photopheresis. The average survival of patients treated with photopheresis was around 50 weeks in comparison with the Mycosis Fungoides Study Group data reporting for the same type of patients a 30 weeks survival using conventional therapies. Photopheresis has been recently used in the rejection control after heart transplantation and in the treatment of AIDS and several autoimmune diseases as pemphigus, sclerodermia, rheumatoid arthritis, LES. The preliminary therapeutic results are very encouraging for a larger use of photopheresis in the treatment of T cell mediated diseases.

Autoimmune Diseases↗
PubMed1994

Role of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection.

Photopheresis is a pheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life, as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon alfa, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens have also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of TNF alfa, and, perhaps, to the induction of anti-clonotypic immunity directed against pathogenic clones of T-lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could beneficially effect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmune Diseases↗
PubMed1994

Treatment of severe atopic dermatitis with extracorporeal photopheresis.

Extracorporeal photopheresis using UVA irradiation of enriched lymphocytes in the presence of 8-methoxypsoralen (8-MOP) as a photoactivatable substrate has been employed for the treatment of several immunologically mediated disorders. We report on the first three patients subjected to extracorporeal photopheresis for severe atopic dermatitis. All patients had a lifelong history of atopic skin inflammation, and their disease had finally become resistant to well-established therapeutic regimes. Extracorporeal photopheresis resulted in a marked clinical improvement in the skin lesions of all patients. The decrease in cutaneous inflammatory activity became evident by the end of the second photopheresis cycle. In two patients skin lesions had virtually disappeared after the fifth treatment cycle, while in the third patient a lasting and substantial improvement in pruritus and erythema was achieved. Clinical remission was stable under maintenance therapy with prolonged intervals between photopheresis sessions. Therapeutic efficacy was reflected by a marked reduction in IgE serum levels in all three patients, while serum concentration of IgG, IgM and IgA as well as the profile of circulating lymphocytes remained essentially unchanged. No clinical signs of immunosuppression or other severe adverse events became evident. Collectively, our preliminary results indicate that extracorporeal photopheresis may interfere with the pathomechanisms leading to atopic dermatitis and therefore should be considered as a treatment modality for severe forms of this recalcitrant disorder.

Adult↗