Photopheresis

from Wikipedia, the free encyclopedia

Photopheresis (also extracorporeal photopheresis; English extracorporeal photopheresis , ECP) ​​is a cell-based immunomodulatory therapy in medicine , which is based on the principles of leukapheresis, photoactivation and UV radiation of the blood and represents a method for the treatment of various immunological diseases.

Basics

Working principle

During the procedure, the leukocyte film (white blood cells and platelets) is separated from the whole blood ( leukapheresis ), chemically treated with 8-methoxypsoralen outside the body , irradiated with UVA light and then re-injected into the patient. As a result of light activation, the 8-methoxypsoralen binds irreversibly to both strands of the DNA , causing apoptosis in the treated leukocytes .

After re-infusion, these apoptotic cells trigger an anti-tumor effect in the treatment of T-cell lymphoma and a tolerogenic effect in the treatment of rejection reactions . It is assumed that pathogenic T cells are phagocytosed by immature dendritic cells , then mature and present the pathogenic T cell receptor as an antigen . This in turn leads to a specific immune reaction against cells with this pathogenic T-cell receptor. A similar process also takes place in the treatment of rejection reactions or autoimmune diseases: Alloreactive or autoreactive activated T cells are subject to apoptosis more quickly than resting T cells and are therefore preferentially absorbed by immature dendritic cells. After maturation, the dendritic cells in turn present T-cell antigens that are associated with allo- or autoreactive activated T-cells. This then triggers a specific immune reaction against the activated T cells. In this way, a specific elimination of pathogenic T cells can be achieved without a general immunosuppression . However, the exact mechanism is not fully understood.

In addition, in the treatment of GVHD, an increased release of anti-inflammatory cytokines and a reduction in inflammatory cytokines, as well as an increased production of regulatory T cells, are observed.

The treatment with photopheresis takes place in several cycles, whereby a cycle usually consists of two successive photopheresis treatments. The treatment regimen, i.e. the number of cycles and the interval between two cycles, differs depending on the disease. Blood is usually drawn from a peripheral venous access.

history

The immunological effects of psoralen treated with UVA radiation have long been known in medicine as PUVA therapy. The photopheresis approach, only exposing the leukocytes to UVA radiation and thus avoiding the carcinogenic risks of UVA radiation for the skin, was first used in 1987 in the treatment of cutaneous T cell lymphoma . In 1988 the first photopheresis system was approved by the American FDA .

application

Cutaneous T-cell lymphoma

The use of extracorporeal photopheresis (ECP) is recommended as a first-line therapy for cutaneous T-cell lymphoma in erytrodermic mycosis fungoides (MF) with stage III or IV and for Sézary syndrome . For other stages of mycosis fungoides, photopheresis is recommended as a second-line therapy in patients who do not respond to skin-specific therapies. The treatment is carried out once or twice a month on two consecutive days for at least six months, and more frequently in patients with a high disease burden.

Graft-versus-Host Disease

In acute graft-versus-host disease (aGvHD) after stem cell transplantation , photopheresis is recommended as a second-line therapy in patients with aGvHD grade II to IV. ECP should be considered particularly in patients who do not respond to systemic corticosteroids , who cannot tolerate them, or who cannot be discontinued ( steroid dependency ). The ECP should be used as soon as possible, initially three times a week, then twice a week until the disease resolves.

A systematic survey of the largest German-speaking treatment centers is available on the importance that the ECP has acquired in the treatment of aGvHD in everyday clinical practice: In the survey of 43 treatment centers in Germany and Switzerland from 2013, the ECP was after Mycophenolat-Mofetil ( MMF) the most widely used second-line therapy for aGVHD, which is used by around 70% of all treatment centers in everyday clinical practice.

In chronic graft-versus-host disease (cGVHD), photopheresis is also recommended as a second-line therapy after unsuccessful treatment with systemic corticosteroids. Photopheresis is usually used twice a week for at least 3 months.

Of the available second-line therapies, the ECP has the highest level of evidence of all second-line therapies with class II evidence and a grade of recommendation of C-1 according to the guidelines of the German Society for Hematology and Medical Oncology .

Rejection reactions after solid organ transplantation

Photopheresis is also used to avoid or weaken rejection reactions after organ transplants . In the treatment of recurrent or resistant rejection after heart transplantation , photopheresis is recommended as a second-line therapy because it can help with severe rejection and reduce the risk of recurrent hemodynamic decompensation . After heart transplants, photopheresis is usually used twice a week for one to three weeks. In the treatment of bronchiolitis obliterans syndrome (BOS) after a lung transplant , photopheresis is used in patients whose disease does not respond to intensified immunosuppression and macrolide antibiotics . It is also used after kidney transplants as a treatment option for rejection reactions or as a prophylaxis against rejection.

Systemic sclerosis

Photopheresis is recommended as a second line therapy to treat skin involvement in systemic sclerosis . It is recommended to use the ECP in early progressive courses, preferably with a disease duration of less than two years, if patients have not previously responded to methotrexate , mycophenolate mofetil or cyclophosphamide . Usually two applications on two consecutive days every 4 - 6 weeks for 6 - 12 months are recommended, followed by monthly treatments as long-term therapy.

Bronchiolitis obliterans

In this inflammatory disease of the bronchioles, photopheresis can be used for patients who do not respond to immunosuppressants or macrolide antibiotics.

Other diseases

Photopheresis is also recommended for very severe forms of atopic eczema , when cyclosporine and other immunosuppressants are not effective or contraindicated, and for treatment-resistant lichen planus , especially when food intake is restricted, there is weight loss or the development of squamous cell carcinoma is threatened.

Photopheresis can also be used for persistent courses of pemphigus , when conventional therapies have failed and are being considered as a therapeutic alternative in therapy-refractory patients with autoimmune blistering dermatoses .

Initial studies of the treatment of steroid- dependent Crohn's disease patients using photopheresis showed good tolerability and could halt the progression of the disease for some patient groups. So far, however, the study situation is not sufficient for clear treatment recommendations.

Web links

Individual evidence

  1. ↑ a b c d Meinhard Schiller, Claus-Detlev Klemke et al .: S1 guideline - extracorporeal photopheresis. (PDF) In: AWMF-Register 013/072. Dermatological Oncology Working Group (ADO), German Cancer Society and German Dermatological Society, accessed on April 26, 2018 .
  2. ↑ Dalil Hannani: Extracorporeal Photopheresis: Tolerogenic or Immunogenic Cell Death? Beyond Current Dogma . In: Frontiers in Immunology . tape 6 , 2015, ISSN  1664-3224 , doi : 10.3389 / fimmu.2015.00349 , PMID 26217341 , PMC 4493405 (free full text).
  3. ↑ James W. Hart, Lisa H. Shiue, Elizabeth J. Shpall, Amin M. Alousi: Extracorporeal photopheresis in the treatment of graft-versus-host disease: evidence and opinion . In: Therapeutic Advances in Hematology . tape 4 , no. 5 , October 2013, ISSN  2040-6207 , p. 320–334 , doi : 10.1177 / 2040620713490316 , PMID 24082993 , PMC 3766348 (free full text).
  4. ^ RL Edelson: Photopheresis: a new therapeutic concept. In: The Yale Journal of Biology and Medicine . tape 62 , no. 6 , 1989, pp. 565-577 , PMID 2700056 , PMC 2589156 (free full text).
  5. ↑ Premarket Approval (PMA). Retrieved August 20, 2018 .
  6. ↑ a b Arun Alfred, Peter C. Taylor, Fiona Dignan, Khaled El-Ghariani, James Griffin: The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society . In: British Journal of Hematology . tape 177 , February 21, 2017, p. 287-310 , doi : 10.1111 / bjh.14537 , PMID 28220931 , PMC 5412836 (free full text).
  7. ↑ Franz Trautinger, Robert Knobler, clean Willemze, Ketty Peris, Rudolph Stadler: EORTC consensus recommendations for the treatment of mycosis fungoides / Sezary syndrome . In: European Journal of Cancer (Oxford, England: 1990) . tape 42 , no. 8 , May 2006, p. 1014-1030 , doi : 10.1016 / j.ejca.2006.01.025 , PMID 16574401 .
  8. ↑ Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani: Chronic lymphocytic leukemia / small lymphocytic lymphoma, version 1.2015 . In: Journal of the National Comprehensive Cancer Network: JNCCN . tape 13 , no. 3 , March 2015, p. 326-362 , PMID 25736010 , PMC 4841457 (free full text).
  9. ^ E. Das-Gupta, F. Dignan, B. Shaw, K. Raj, R. Malladi: Extracorporeal photopheresis for treatment of adults and children with acute GVHD: UK consensus statement and review of published literature . In: Bone Marrow Transplant . tape 49 , no. 10 , October 2014, p. 1251–1258 , doi : 10.1038 / bmt.2014.106 , PMID 24887389 .
  10. ^ Robert Zeiser, Daniel Wolff, Christof Scheid, Thomas Luft, Hildegard Greinix, Peter Dreger, Jürgen Finke, Ernst Holler: DGHO guidelines of the German Society for Hematology and Medical Oncology eV Graft-versus-host disease, acute: Recommendations of the specialist society for diagnostics and therapy of haematological and oncological diseases. (PDF) DGHO German Society for Hematology and Medical Oncology eV, March 2018, accessed on April 26, 2018 .
  11. ↑ Daniel Wolff, Francis Ayuk, Ahmet Elmaagacli, Hartmut Bertz, Anita Lawitschka: Current practice in diagnosis and treatment of acute graft-versus-host disease: results from a survey among German-Austrian-Swiss hematopoietic stem cell transplant centers . In: Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation . tape 19 , no. 5 , January 31, 2013, p. 767-776 , doi : 10.1016 / j.bbmt.2013.01.018 , PMID 23376495 .
  12. ^ A b Daniel Wolff, Robert Zeiser, Christof Scheid, Thomas Luft, Stephan Mielke, Peter Dreger, Jürgen Finke, Ernst Holler, Hildegard Greinix: DGHO guidelines of the German Society for Hematology and Medical Oncology eV Graft-versus-host disease, chronic: Recommendations of the professional society for diagnosis and therapy of haematological and oncological diseases. (PDF) DGHO German Society for Hematology and Medical Oncology eV, March 2018, accessed on April 26, 2018 .
  13. ↑ Fiona L. Dignan, Persis Amrolia, Andrew Clark, Jacqueline Cornish, Graham Jackson: Diagnosis and management of chronic graft-versus-host disease . In: British Journal of Hematology . tape 158 , no. 1 , July 2012, p. 46-61 , doi : 10.1111 / j.1365-2141.2012.09128.x , PMID 22533811 .
  14. ↑ Markus J. Barten, Uwe Schulz, Andres Beiras-Fernandez, Michael Berchtold-Herz, Udo Boeken: The clinical impact of donor-specific antibodies in heart transplantation . In: Transplant Reviews . May 8, 2018, doi : 10.1016 / j.trre.2018.05.002 , PMID 29804793 .
  15. ↑ David Taylor, Bruno Meiser , Steven Webber: ISHLT Guidelines for the Care of Heart Transplant Recipients: Task Force 2: Immunosuppression and Rejection. (PDF) In: The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. November 8, 2010, accessed April 28, 2018 .
  16. ↑ Federal Department of the Interior grants reimbursement approval for extracorporeal photopheresis (ECP), including the ECP immunomodulation THERAKOS® from Mallinckrodt . In: presseportal.de . August 23, 2016 ( presseportal.de [accessed April 26, 2018]).
  17. ↑ M. Kusztal, K. Kościelska-Kasprzak, W. Gdowska, M. Żabińska, M. Myszka: Extracorporeal Photopheresis as an Antirejection Prophylaxis in Kidney Transplant Recipients: Preliminary Results . In: Transplantation Proceedings . tape 43 , no. 8 , October 2011, p. 2938-2940 , doi : 10.1016 / j.transproceed.2011.08.061 .
  18. ↑ R. Knobler, P. Moinzadeh, N. Hunzelmann, A. Kreuter, A. Cozzio: European Dermatology Forum S1 guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes . In: Journal of the European Academy of Dermatology and Venereology: JEADV . tape 31 , no. 9 , September 2017, p. 1401-1424 , doi : 10.1111 / jdv.14458 , PMID 28792092 .
  19. ↑ Annice Heratizadeh et al .: Guideline (S2k) Neurodermitis long version. (PDF) German Dermatological Society (DDG), March 2015, accessed on April 26, 2018 .
  20. ^ KE Harman, S. Albert, MM Black, British Association of Dermatologists: Guidelines for the management of pemphigus vulgaris . In: The British Journal of Dermatology . tape 149 , no. 5 , November 2003, p. 926-937 , PMID 14632796 .
  21. ↑ R. Knobler, G. Berlin, P. Calzavara-Pinton, H. Greinix, P. Jaksch: Guidelines on the use of extracorporeal photopheresis . In: Journal of the European Academy of Dermatology and Venereology: JEADV . 28 Suppl 1, January 2014, p. 1–37 , doi : 10.1111 / jdv.12311 , PMID 24354653 , PMC 4291097 (free full text).
  22. ^ W Reinisch, H. Nahavandi, R. Santella, Y. Zhang, C. Gasché: Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study . In: Alimentary Pharmacology & Therapeutics . tape 15 , no. 9 , September 2001, p. 1313-1322 , PMID 11552901 .