Feasibility and safety of a new technique of extracorporeal photochemotherapy: experience of 240 procedures.
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BACKGROUND AND OBJECTIVE: Extracorporeal photochemotherapy (ECP) is a therapeutic approach based on the biological effects of ultraviolet light (UV) - A and psoralens on mononuclear cells collected by apheresis. Recently, ECP has been under investigation as an alternative treatment for various immune and autoimmune diseases. The aim of this study was to evaluate the safety and feasibility of a new three-step ECP technique, in terms of reproducibility, acceptance, tolerability, and short and long term side effects. DESIGN AND METHODS: Seventeen patients affected by acute or chronic graft-versus-host disease (GvHD), pemphigus vulgaris, or interferon-resistant chronic hepatitis C and one patient being treated for prevention of heart transplant rejection underwent 240 ECP procedures. MNC collection and processing parameters were recorded, biological effects of UV-A/8 methoxy-psoralen (8-MOP) were evaluated, and short and long term side effects were monitored. RESULTS: At a mean follow up of 7 months (range 2-19) 240 ECP had been completed, a mean of 7,136 mL (range 1,998-10,591) of whole blood having beenprocessed per procedure. The mean of total nucleated cells collected per procedure was 6.5x109 (range 0.65-23.8), with a mean MNC percentage of 85% (41. 4-98%) in a mean final volume of 115.5 mL (37-160). No severe side effects were documented and no infectious episodes occurred throughout the course of the treatment. INTERPRETATION AND CONCLUSIONS: The new ECP technique was highly reproducible as regards the collection and each processing step. Short and long term side effects were mild. No increase in infectious episodes was recorded. All patients willingly underwent ECP, demonstrating an excellent tolerability for the procedure even after several courses. (+info)
Extracorporeal photopheresis (ECP) in the treatment of chronic graft-versus-host disease (GVHD)
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The aim of our study was to assess the efficacy of extracorporeal photopheresis (ECP) in chronic graft-versus-host disease (GVHD). Eleven patients with chronic cutaneous GVHD were studied. Four had mucosal involvement and five had pulmonary involvement. All had failed to improve on first- and second-line therapy. Three patients received ECP alone; the remainder continued to receive steroids and/or immunosuppressive therapy. Patients received ECP twice monthly for 4 months and then once monthly for 3 months. They were evaluated by serial skin scores, mucosal and skin photography, pulmonary function tests, biochemical and haematological parameters. Nine patients showed objective evidence of cutaneous improvement with a mean reduction in skin score of 48% overall. In the 10th patient, skin scores and oral involvement improved on twice monthly ECP but deteriorated when reduced to once monthly. The final patient died from renal failure secondary to cyclosporin toxicity. Two out of five patients with lung involvement showed a mild improvement in pulmonary function tests. Liver function tests were abnormal in five patients; they improved in one and deteriorated in three. All patients receiving concomitant immunosuppressive/steroid therapy were able to reduce drug dosages by trial completion. Our results indicate that ECP can benefit patients with cutaneous and mucosal chronic GVHD who have failed on first- and second-line therapies. The effect on the systemic manifestations of GVHD is less consistent. (+info)
Successful reversal of recalcitrant hepatic allograft rejection by photopheresis.
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Extracorporeal photopheresis (ECP) is an immunologic modality that has shown efficacy in the treatment of clonal T-cell diseases, including Sezary syndrome and allograft rejection. In this case report, we expand on this observation to include recalcitrant hepatic allograft rejection. A 14-year-old boy with hepatic allograft rejection refractory to high-dose corticosteroid and lymphocytolytic therapy was treated with 4 sessions of ECP over a 6-week period. After 2 sessions, a liver biopsy showed complete reversal of acute cell-mediated rejection. No opportunistic infections or other adverse events were noted. Photopheresis appears to be a safe and effective modality for the treatment of refractory hepatic allograft rejection. (+info)
Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study.
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Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and UV-A radiation has been shown to be effective in the treatment of selected diseases mediated by T cells, rejection after solid organ transplantation, and chronic graft-versus-host disease (GVHD). We present 21 patients with a median age of 38 years who developed steroid-refractory acute GVHD grades II to IV after stem cell grafting from sibling or unrelated donors and were referred to extracorporeal photochemotherapy (ECP). Three months after initiation of ECP 60% of patients achieved a complete resolution of GVHD manifestations. Complete responses were obtained in 100% of patients with grade II, 67% of patients with grade III, and 12% of patients with grade IV acute GVHD. Three months after start of ECP complete responses were achieved in 60% of patients with cutaneous, 67% with liver, and none with gut involvement. Adverse events observed during ECP included a decrease in peripheral blood cell counts in the early phase after stem cell transplantation (SCT). Currently, 57% of patients are alive at a median observation time of 25 months after SCT. Probability of survival at 4 years after SCT is 91% in patients with complete response to ECP compared to 11% in patients not responding completely. Our findings suggest that ECP is an effective adjunct therapy for acute steroid-refractory GVHD with cutaneous and liver involvement. However, in patients with acute GVHD grade IV or gut involvement other therapeutic options are warranted. (+info)
Photopheresis at onset of type 1 diabetes: a randomised, double blind, placebo controlled trial.
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BACKGROUND: In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. AIM: To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. METHODS: A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included; 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). RESULTS: The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no difference between the groups regarding HbA1c values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. CONCLUSION: Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up. (+info)
Extracorporeal photopheresis in Sezary syndrome: hematologic parameters as predictors of response.
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Data were analyzed from 23 patients with Sezary syndrome (defined by erythroderma, more than 10% circulating atypical mononuclear cells, and peripheral blood T-cell clone) undergoing monthly extracorporeal photopheresis as the sole therapy for up to 1 year. The cohort showed a significant reduction of skin scores during treatment (P =.001). Thirteen patients (57%) achieved a reduction in skin score greater than 25% from baseline at 3, 6, 9, or 12 months (responders). Reduction in skin score correlated with reduction in the Sezary cell count as a percentage of total white cell count (P =.03). Responders and nonresponders were compared. None of the measured parameters was significantly different between the 2 groups. It was assessed whether any of the baseline parameters predicted outcome. A higher baseline lymphocyte count was significantly associated with a decrease in skin score at 6 months (P <.05). A higher baseline Sezary cell count as a percentage of total white cell count predicted a subject was more likely to be a responder after 6 months of treatment (P =.021). No other parameters predicted responder status. These data show that the modest falls in CD4, CD8, and Sezary cell counts were seen in all patients and might have resulted from lymphocyte apoptosis. This mechanism could explain the more favorable response seen in patients with higher percentages of Sezary cells in the peripheral blood. Alternatively, minimum tumor burden might be required for the induction of a cytotoxic response. Analysis of tumor-specific cytotoxic T cells is needed to investigate these possibilities further. (+info)
Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study.
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BACKGROUND: Extracorporeal photochemotherapy has been proven effective in selected T-cell mediated diseases. AIM: To evaluate the safety and efficacy of extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease by an open, monocentric trial in three phases of 24 weeks each. METHODS: In phase 1 standardized steroid tapering was initiated in patients with a history of steroid-dependent Crohn's disease. Those with a prospectively evaluated maintenance dose of at least 10 mg/day prednisolone continued steroid-withdrawal under the application of extracorporeal photochemotherapy in phase 2. The duration of remission or response was followed during phase 3. Colonic tissue bioptically obtained before and after extracorporeal photochemotherapy was studied by immunofluorescence microscopy for the presence of photoadduct positive cells. RESULTS: Out of 24 patients included in phase 1, 10 entered phase 2 for extracorporeal photochemotherapy. Four subjects achieved remission and four others response. Significant reductions in serum C-reactive protein levels and intestinal permeability were measured, as well as increases in quality of life and plasma adrenocorticotropic hormone levels. No major side-effects were observed. Remission remained stable in three out of four patients during phase 3. In three patients, positive nuclear stainings of photoadducts were detected in colonic mononuclear cells after extracorporeal photochemotherapy. CONCLUSIONS: Extracorporeal photochemotherapy represents a safe steroid-sparing approach in patients with Crohn's disease and is associated with intestinal homing of photopheresed cells. (+info)
Cutaneous T-cell lymphoma in a cardiac transplant recipient.
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Mycosis fungoides, an uncommon form of cutaneous T-cell lymphoma, arises in the skin and frequently progresses to generalized lymphadenopathy Although the cause of cutaneous T-cell lymphoma is unknown, chronic immunosuppression may play a role. A few cases have been reported in renal transplant recipients; however, ours appears to be the 1st report of cutaneous T-cell lymphoma in a cardiac transplant recipient. In our patient, cutaneous manifestations of the disease were noted less than 1 year after transplantation. Seven years after transplantation, Sezary syndrome, a variant form of mycosis fungoides, was diagnosed by tissue biopsy and flow cytometry analysis. Photopheresis improved symptoms but was not well tolerated because of hemodynamic sequelae. Psoralen and ultraviolet A therapy also improved the patient's skin condition, but a generalized lymphadenopathy developed. The maintenance immunosuppressive regimen was changed from cyclosporine (3 mg/kg/day) and azathioprine to cyclosporine (1.5 mg/kg/day) and cyclophosphamide. Although effective in the short-term, the results of this therapeutic strategy could not be fully evaluated because the patient died of acute myocardial infarction. (+info)