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Extracorporeal photopheresis (photochemotherapy) in the treatment of acute and chronic graft versus host disease: immunological mechanisms and the results from clinical studies

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Abstract

Extracorporeal photopheresis (ECP) is an immunomodulatory alternative for treatment of graft versus host disease (GVHD). The blood is then separated into its various components through apheresis; buffy coat cells are thereafter treated with 8-methoxypsoralen before exposure to ultraviolet light and finally reinfused into the patient. There is a general agreement that this treatment has an anti-GVHD effect, but the mechanisms of action behind this effect are only partly understood. However, altered maturation of dendritic cells (DC) and thereby indirect modulation of T-cell reactivity seems to be one important mechanism together with DC-presentation of antigens derived from apoptotic donor T cells and induction of regulatory T cells. The treatment has been best studied in patients with chronic GVHD (both pediatric and adult patients), but most studies are not randomized and it is difficult to know whether the treatment is more effective than the alternatives. The clinical studies of ECP in adults with acute GVHD are few and not randomized; it is not possible to judge whether this treatment should be a preferred second- or third-line treatment. There is no evidence for increased risk of leukemia relapse or suppression of specific graft versus leukemia reactivity by this treatment, so specific antileukemic immunotherapy may still be possible. Thus, even though the treatment seems effective in patients with GVHD, further clinical (especially randomized) as well as biological studies with careful standardization of the treatment are needed before it is possible to conclude how ECP should be used in acute and chronic GVHD.

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Abbreviations

ATG:

Antithymocyte globulin

CSA:

Ciclosporin A

DC:

Dendritic cell

ECP:

Extracorporeal photopheresis

GILZ:

Glucocorticoid-induced leucine zipper

GVHD:

Graft versus host disease

GVL:

Graft versus leukemia

Hb:

Hemoglobin

IFN:

Interferon

IL:

Interleukin

MFM:

Mycofenolate mofetil

8-MOP:

8-methoxypsoralen

mTOR:

Molecular target of rapamycin

MTX:

Methotrexate

MUD:

Matched unrelated donor

NK:

Natural killer

RIC:

Reduced intensity conditioning

SCT:

Stem cell transplantation

Th:

T helper

TNF:

Tumor necrosis factor

UV-A:

Ultraviolet light A

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Acknowledgments

The authors receive financial support for their scientific work from the Norwegian Cancer Society and from Helse-Vest.

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Authors and Affiliations

  1. Section for Hematology, Institute of Clinical Science, University of Bergen, Bergen, Norway

    Øystein Bruserud & Håkon Reikvam

  2. Department of Medicine, Haukeland University Hospital, 5021, Bergen, Norway

    Øystein Bruserud, Tor Henrik Anderson Tvedt, Aymen Bushra Ahmed & Håkon Reikvam

  3. Department for Hematology, St Olavs Hospital, Trondheim, Norway

    Petter Quist Paulsen

  4. Department for Hematology, Oslo University Hospital, Oslo, Norway

    Tobias Gedde-Dahl, Geir E. Tjønnfjord, Heidi Slåstad & Dag Heldal

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Bruserud, Ø., Tvedt, T.H.A., Paulsen, P.Q. et al. Extracorporeal photopheresis (photochemotherapy) in the treatment of acute and chronic graft versus host disease: immunological mechanisms and the results from clinical studies. Cancer Immunol Immunother 63, 757–777 (2014). https://doi.org/10.1007/s00262-014-1578-z

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