Article

Photopheresis and Leukocytapheresis: Cytapheresis Treatment Against Immune-Mediated Diseases

Authors:
To read the full-text of this research, you can request a copy directly from the author.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

Chapter
Fundamentally, apheresis refers to the separation or removal of a blood component. Therapeutic apheresis is the use of this technique to treat or manage pathophysiologic disease states. Apheresis can be used to selectively target removal of plasma (plasmapheresis), red blood cells (erythrocytapheresis), platelets (platletpheresis), and leukocytes (leukapheresis). Additionally, the therapy has evolved and it now allows activating leukocytes (photopheresis) and specifically targeting certain proteins (immunoadsorptoin and LDL-apheresis). Although apheresis has been trialed in a wide variety of disease states, the existing data only supports its use in a subset of those conditions and it is important to make evidence based decisions. In this chapter we review the principles of apheresis, describe the therapies offered, and highlight some of the more common indications. Additionally, we describe the manner in which apheresis must be modified for use in children and place the therapy in the context of pediatric medicine.
Chapter
The term “apheresis” is derived from a Greek word meaning “removal.” In its most general sense, apheresis refers to techniques for large-scale removal of selected components of the blood. “Plasmapheresis” refers to removal of plasma, “erythrocytapheresis” to removal of red blood cells, and “leukapheresis” to removal of white blood cells. In the first part of this chapter we (SLG, DFF, HCK) will give an overview of apheresis techniques in general as currently practiced in the United States, describe some of the issues that are unique to the application of apheresis techniques in pediatrics, and will review indications for use of apheresis in patients with kidney disease. The latter portion of the chapter (GK) is devoted to an in-depth description of low-density lipoprotein (LDL) apheresis, a specialized application of apheresis technology, as it is currently practiced in Europe. © Springer Science+Business Media, LLC 2004, 2012. All rights reserved.
Article
In its most general sense, apheresis refers to techniques for large-scale removal of selected components of the blood. Plasmapheresis refers to removal of plasma, erythrocytapheresis to removal of red blood cells, and leukapheresis to removal of white blood cells. The provision of apheresis for critically ill children is becoming more commonplace as the immunobiology of various acute diseases is becoming elucidated, yet remains challenging due to a number of un-modifiable factors. However, given the relative infrequency of these disorders, prospective randomized trials to evaluate the efficacy of therapeutic apheresis are lacking. In addition, critically ill children develop their maximal organ failures and mortality very early in the intensive care unit time course, so waiting to see if a disease will resolve is often not a clinical option for many of these patients. Finally, many diseases do not have a biological marker to follow, so reliance on clinical improvement can be very subjective. The aim of this chapter is to describe the technical pediatric specific considerations and typical indications for apheresis provision for children seen in the pediatric intensive care unit setting. In addition, a framework for consideration of when to initiate, continue and discontinue therapeutic plasmapheresis is provided.
Article
The provision of therapeutic apheresis to children is a technically challenging procedure, requiring trained personnel and an understanding of the disease processes that leads to the need for apheresis. Most apheresis protocols are derived from studies in adult patients, even though most studies are of limited sample size. The focus of this review is to highlight the disease processes commonly treated with therapeutic apheresis in children, and to address the technical considerations pertinent to the provision of safe and effective apheresis in the pediatric setting.
Article
Over the past several years, research in the field of cytokine production and function has become indispensable to understand the immunopathology of chronic intestinal inflammation. Thereupon, clinical studies analyzing cytokine production have generated a tremendous amount of data. In patients with inflammatory bowel disease, several studies examined pro-inflammatory cytokines in gut tissue and plasma, but a clear interpretation of the results with respect to disease activity or therapeutic response has been hampered by patient- and sample-related pitfalls.
Article
This original cohort of patients with erythrodermic cutaneous T-cell lymphoma (CTCL) was reported to have clinical improvement with photopheresis during the 12 months of the original study. No long-term follow-up data have been available to examine the impact of this therapy on the disease. Our purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL patients treated with photopheresis and to compare these results with historical controls. Files of patients from the original photopheresis study centers were reviewed and their current status was documented. The median survival of the treated patients was 60.33 months from the date of diagnosis and 47.9 months from the date of the start of photopheresis therapy. A complete remission has been maintained in four of the six patients who achieved complete responses in the original study. The best responses were seen in patients with a lower CD4/CD8 ratio in the peripheral blood at the start of therapy. Photopheresis can influence the natural history of erythrodermic CTCL by inducing remissions and prolonging survival with minimal toxicity.
Article
Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.
Article
Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.
Article
Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoactivatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregulatory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.
Article
The present study was designed to determine the efficacy of filtration leukocytapheresis (LCAP) in the treatment of rheumatoid arthritis (RA) with vasculitis. Nine RA patients with vasculitis were studied by the Malignant RA Collaborative Group formed by 8 clinical centers. A total of 7 filtration LCAP procedures using the Cellsorba column (Asahi Medical Co., Ltd., Tokyo, Japan) were performed with 1 week intervals between treatments. During each apheresis procedure, 3,000 ml of blood was filtered and returned to the patient at a flow rate of 50 ml/min for 60 min. In addition to the amelioration of arthritis, the improvement of extraarticular symptoms associated with rheumatoid vasculitis such as polyneuritis, skin ulcers, digital gangrene and rheumatoid nodules was obtained. In contrast, no improvement was observed in interstitial pneumonia or lung fibrosis. LCAP could be an optional modality for the treatment of RA with vasculitis.
Article
Extracorporeal photochemotherapy (ECP) was introduced by Edelson and co-workers in 1985. Since then the therapy, though still controversial in specific indications, has received wide acceptance and is presently been used in over 160 centers in Europe and the U.S.A. for a number of important dermatological and non-dermatological indications. Convincing data in the past few years has documented that ECP is associated with a very low side-effect profile. As of 2000 ECP continues to be used in the treatment of cutaneous T-cell lymphoma, alone or in combination with other treatment modalities, and increasingly in the management of additional T-cell mediated diseases, acute as well as chronic Graft versus Host Disease (GvHD) after allogeneic bone marrow transplantation in particular. ECP has also been shown to play an important role in the treatment of acute as well as chronic allograft rejection, in renal, lung, and cardiac transplant recipients and lately steroid refractory inflammatory bowel disease. A number of mechanisms for its efficacy have been proposed whereby at present induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes may be an important concept. Treatment related apoptotic death of involved T cells and concurrent activation of antigen presenting cells may also closely relate to mechanisms associated with this therapy.
Article
We prospectively examined the effect of leukocytapheresis (LA) on the maintenance of remission in 7 patients with ulcerative colitis (UC) who were initially refractory to corticosteroid therapy (steroid resistant or steroid dependent). The patients with refractory UC had been in remission due to LA (induction LA) in combination with the steroid therapy. They were then treated with LA once or twice a month for the purpose of maintaining remission (maintenance LA). The maintenance LA was performed by either a centrifuge method in 5 patients or a polyester adsorbent column method in 2 patients. Steroid dosage was gradually tapered as little as possible without recurrence based on clinical and/or colonoscopical judgments. Four patients were maintained in remission without steroids over 12 months. Recurrence was observed in 3 patients at 3, 3, and 6 months after the beginning of the maintenance LA, respectively. Two of the 3 patients were again conducted to remission by the second induction LA and maintained in remission by the second maintenance LA. Two patients finally underwent total colectomy because of recurrence of UC in a severe form. It is concluded that the maintenance LA therapy might be effective in some patients with steroid dependent or resistant UC for the maintenance of remission without steroids.