Read Time: 2 mins

The Use of Extracorporeal Photopheresis for the Treatment of Acute Graft Versus Host Disease

Copy Link
Published Online: Aug 5th 2012 European Oncology & Haematology, 2012;8(4):249-253 DOI:
Authors: Emma Das-Gupta
Quick Links:
Article Information

Acute graft versus host disease (aGVHD) is a key complication of haematopoietic stem-cell transplantation. The main first-line therapy is steroids, however less than half of patients respond to this treatment, and some patients relapse following an initial response. Extracorporeal photopheresis (ECP) is a therapy that has shown promising efficacy in several immune-mediated disorders, including aGVHD. Used as a second-line treatment, ECP has been associated with good rates of disease resolution, both overall and for individual organ systems involved in this disorder. The responses to ECP have commonly been seen soon after the start of treatment. Patients who respond to ECP have also been shown to have lower rates of transplant-related mortality and greater overall survival than those who do not respond. ECP is well tolerated by patients, including those with a low performance index and children of low body weight. Data on the use of ECP in treating aGVHD in both adults and children are reviewed here.


Acute graft versus host disease (aGVHD), extracorporeal photopheresis, adult, paediatric, complete resolution, transplant-related mortality, survival, tolerability, safety


Graft versus host disease (GVHD) is a major complication of haematopoietic stem-cell transplantation (HSCT). Historically, GVHD occurring within the first 100 days post HSCT was classified as acute GVHD (aGVHD). More recently, the National Institutes of Health (NIH) consensus criteria for clinical trials proposed that clinical manifestations rather than time after transplantation should be used to distinguish acute from chronic GVHD and introduced the term late acute GVHD, which includes persistent, recurrent, or late-onset aGVHD.1 Clinical manifestations of aGVHD involve the skin, gastrointestinal tract and liver.2 The incidence of aGVHD is reported to range from 10 to 80 %, depending on risk factors such as the use of unrelated donors, total body irradiation and transplant conditioning regimen.3 Acute GVHD is, in turn, a strong risk factor for transplant-related morbidity and mortality (TRM), because of its own pathology and that associated with the immunosuppressive therapies generally used for its treatment. It is also a risk factor for the development of chronic GVHD.

Corticosteroids are the main first-line therapy for aGVHD, however these are associated with a response in less than 50 % of patients,4 and some patients who initially respond subsequently relapse.5 Response after short-term treatment with prednisolone (five days or 28 days) was significantly associated with a lower TRM than non-response.6,7 New therapies are therefore being investigated that can quickly and effectively treat aGVHD, and prevent its relapse. One such therapy is extracorporeal photopheresis (ECP).

ECP is a therapy that was originally developed over 25 years ago to treat cutaneous T-cell lymphoma.8 Since that time, its use has been investigated and shown promising efficacy in many other disorders with an auto- or alloimmune aetiology, including GVHD, systemic sclerosis, prevention and treatment of rejection in solid organ transplantation and Crohn’s disease.9 The treatment has three stages: first leukapheresis, following which the separated white blood cells are photoactivated with 8-methoxypsoralen and exposure to ultraviolet-A light, then return of the activated white blood cells to the patient. ECP has been found to be generally well tolerated, with a good safety profile, in patients with a variety of diseases.10 This paper reviews studies with ECP in patients with aGVHD.

To view the full article in PDF or eBook formats, please click on the icons above.

Article Information:

Speaker at an aGVHD meeting in Paris, January 2011, organised by Therakos.


Emma Das-Gupta, Centre for Clinical Haematology, Nottingham University Hospitals, City Hospital Campus, Hucknall Road, Nottingham, NG5 1PB, UK. E:


Educational grant from Therakos to attend ASH, December 2009.




  1. Filipovich AH, Weisdorf D, Pavletic S, et al., National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report, Biol Blood Marrow Transplant, 2005;11:945–56.
  2. Dignan FL, Clark A, Amrolia P, et al., BCSH/BSBMT guideline: diagnosis and management of acute graft-versus-host disease, Br J Haematol, 2012;158(1):30−45.
  3. Flowers MED, Inamoto Y, Carpenter PA, Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria, Blood, 2011;117(11):3214−9.
  4. Martin PJ, Schoch G, Fisher L, et al., A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment, Blood, 1990;76(8):1464–72.
  5. Baird K, Wayne AS, Extracorporeal photo-apheresis for the treatment of steroid-resistant graft versus host disease, Transfus Apher Sci, 2009;41:209–16.
  6. MacMillan ML, DeFor TE, Weisdorf DJ, The best endpoint for acute GVHD treatment trials, Blood, 2010;115(26):5412–7.
  7. Van Lint MT, Milone G, Leotta S, et al., Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin, Blood, 2006;107:4177–81.
  8. Edelson RL, Berger C, Gasparro F, et al., Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy: preliminary results, N Engl J Med, 1987;316:297–303.
  9. Knobler R, Barr ML, Couriel DR, et al., Extracorporeal photopheresis: past, present, and future, J Am Acad Dermatol, 2009;61:652–65.
  10. Scarisbrick J. Extracorporeal photopheresis: what is it and when should it be used?, Clin Exp Dermatol, 2009;34:757–60.
  11. Dall'Amico R, Messina C. Extracorporeal photochemotherapy for the treatment of graft-versus-host disease, Ther Apher, 2002;6(4):296–304.
  12. Sniecinski I, Smith B, Parker PM, Dagis A, Extracorporeal photochemotherapy for treatment of drug resistant chronic graft-versus-host disease, J Clin Apher, 1995:10:51.
  13. Besnier DP, Chabannes D, Mahe B, et al., Treatment of graftversus- host disease by extracorporeal photochemotherapy: a pilot study, Transplantation, 1997;64:49–54.
  14. Looks A, Fuchjs D, Rulke D, et al., Successful treatment of acute graft versus host disease after bone marrow transplantation in a 16-year-old girl with extracorporeal photopheresis, Onkologie, 1997;20:340–2.
  15. Richter HI, Stege H, Ruzicka T, et al., Extracorporeal photopheresis in the treatment of acute graft-versus-host disease, J Am Acad Dermatol, 1997;36:787–9.
  16. Greinix HT, Volc-Platzer B, Rabitsch W, et al., Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease, Blood, 1998;92:3098–104.
  17. Miller JL, Goodman SA, Stricklin GP, Lloyd EK, Extracorporeal photochemotherapy in the treatment of graft-versus-host disease, abstract book IBMTR/ABMTR Meeting, Keystone Resort Colorado,1998;7a.
  18. Smith EP, Sniecinski I, Dagis AC, et al., Extracorporeal photochemotherapy for treatment of drug-resistant graft-vshost disease, Biol Blood Marrow Transplant, 1998;4:27−37.
  19. Girardi M, McNiff JM, Heald PW, Extracorporeal photochemotherapy in human and murine graft-versus-host disease, J Dermatol Sci, 1999;9:106–13.
  20. Greinix HT, Volc-Platzer B, Kalhs P, et al., Extracorporeal photochemotherapy in the treatment of severe steroidrefractory acute graft-versus-host disease: a pilot study, Blood, 2000;96:2426–31.
  21. Salvaneschi L, Perotti C, Zecca M, et al., Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood, Transfusion, 2001;41:1299–305.
  22. Greinix HT, Knobler RM, Worel N, et al., The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease, Haematologica, 2006;91(3):405–8.
  23. Greinix HT, Worel N, Knobler R, Role of extracorporeal photopheresis (ECP) in treatment of steroid-refractory acute graft-versus-host disease, Biol Blood Marrow Transplant, 2010;16:1747–8.
  24. Garban F, Drillat P, Makowski C, et al., Extracorporeal chemophototherapy for the treatment of graft-versus-host disease: hematologic consequences of short-term, intensive courses, Haematologica, 2005;90(8):1096–101.
  25. Perfetti P, Carlier P, Strada P, et al., Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD, Bone Marrow Transplant, 2008;42(9):609–17.
  26. Robin M, Jagasia M, Greinix H, et al., Extracorporeal photopheresis compared to systemic immunosuppressive as second line therapy for steroid dependent and refractory acute graft-versus-host disease: international multi-center study, Bone Marrow Transplant, 2012;47(Suppl 1):S12(Abs O123).
  27. Messina C, Locatelli F, Lanino E, et al., Extracorporeal photochemotherapy for paediatric patients with graftversus- host disease after haematopoietic stem cell transplantation, Br J Haematol, 2003;122(1):118–27.
  28. Berger M, Pessolano R, Albiani R, et al., Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report, J Pediatr Hematol Oncol, 2007;29(10):678–87.
  29. Gonzalez-Vicent M, Ramirez M, Perez A, et al., Extracorporeal photochemotherapy for steroid-refractory graft-versus-host disease in low-weight pediatric patients. Immunomodulatory effects and clinical outcome, Haematologica, 2008;93(8):1278–80.
  30. Kanold J, Merlin E, Halle P, et al., Photopheresis in pediatric graft-versus-host disease after allogeneic marrow transplantation: clinical practice guidelines based on field experience and review of the literature, Transfusion, 2007;47(12):2276–89.
  31. Calore E, Calo A, Tridello G, et al., Extracorporeal photochemotherapy may improve outcome in children with acute GVHD, Bone Marrow Transplant, 2008;42(6):421–5.
  32. Perotti C, Del Fante C, Tinelli C, et al., Extracorporeal photochemotherapy in graft-versus-host disease: a longitudinal study on factors influencing the response and survival in pediatric patients, Transfusion, 2010;50(6):1359–69.
  33. Schneiderman J, Jacobsohn DA, Collins J, et al., The use of fluid boluses to safely perform extracorporeal photopheresis (ECP) in low-weight children: a novel procedure, J Clin Apher, 2010;25(2):63–9.
  34. Miller KB, Roberts TF, Chan G, et al., A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease, Bone Marrow Transplant, 2004;33(9):881–9.
  35. Shaughnessy PJ, Bolwell BJ, van Besien K, et al., Extracorporeal photopheresis for the prevention of acute GVHD in patients undergoing standard myeloablative conditioning and allogeneic hematopoietic stem cell transplantation, Bone Marrow Transplant, 2009;45(6):1068–76.
  36. Pidala J, Anasetti C, Glucocorticoid-refractory acute graftversus- host disease, Biol Blood Marrow Transplant, 2010;16(11):1504–18.

Further Resources

Share this Article
  • Copied to clipboard!
    accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72