Extracorporeal photopheresis for treatment of adults and children with acute GVHD: UK consensus statement and review of published literature

Das‐Gupta, Emma; Dignan, Fiona L.; Shaw, Bronwen E.; Raj, Kavita; Malladi, Ram; Gennery, Andrew R.; Bonney, Denise; Taylor, Peter; Scarisbrick, Julia

doi:10.1038/bmt.2014.106

Cited by 42 publications

(31 citation statements)

References 36 publications

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“…The incidence of grade II–IV aGvHD in children ranges from 28 to 56% (49), depending on the degree of histocompatibility, recipient age, underlying condition, and conditioning regimen used (50). Higher aGvHD grades have consistently been associated with worse transplant-related mortality (TRM) and lower overall survival rates (51). …”

Section: Graft-versus-host Diseasementioning

confidence: 99%

Treatment of Pediatric Acute Graft-versus-Host Disease—Lessons from Primary Immunodeficiency?

Flinn

Gennery

2017

Front. Immunol.

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Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in improved human leukocyte antigens-typing techniques, less toxic conditioning regimens and better supportive care, resulting in improved clinical outcomes, acute graft-versus-host disease (aGvHD) continues to be a major obstacle and, although it principally involves the skin, gastrointestinal tract, and liver, the thymus is also a primary target. An important aim following HSCT is to achieve complete and durable immunoreconstitution with a diverse T-cell receptor (TCR) repertoire to recognize a broad range of pathogens providing adequate long-term adaptive T-lymphocyte immunity, essential to reduce the risk of infection, disease relapse, and secondary malignancies. Reconstitution of adaptive T-lymphocyte immunity is a lengthy and complex process which requires a functioning and structurally intact thymus responsible for the production of new naïve T-lymphocytes with a broad TCR repertoire. Damage to the thymic microenvironment, secondary to aGvHD and the effect of corticosteroid treatment, disturbs normal signaling required for thymocyte development, resulting in impaired T-lymphopoiesis and reduced thymic export. Primary immunodeficiencies, in which failure of central or peripheral tolerance is a major feature, because of intrinsic defects in hematopoietic stem cells leading to abnormal T-lymphocyte development, or defects in thymic stroma, can give insights into critical processes important for recovery from aGvHD. Extracorporeal photopheresis is a potential alternative therapy for aGvHD, which acts in an immunomodulatory fashion, through the generation of regulatory T-lymphocytes (Tregs), alteration of cytokine patterns and modulation of dendritic cells. Promoting normal central and peripheral immune tolerance, with selective downregulation of immune stimulation, could reduce aGvHD, and enable a reduction in other immunosuppression, facilitating thymic recovery, restoration of normal T-lymphocyte ontogeny, and complete immunoreconstitution with improved clinical outcome as the ability to fight infections improves and risk of secondary malignancy or relapse diminishes.

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Section: Graft-versus-host Diseasementioning

confidence: 99%

Treatment of Pediatric Acute Graft-versus-Host Disease—Lessons from Primary Immunodeficiency?

Flinn

Gennery

2017

Front. Immunol.

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“…Extracorporeal photopheresis is by UK and Italian scientific/clinical consensus groups recommended as 2 nd -line treatment for graft-versus-host disease (GvHD) after allogeneic stem cell transplantation and for scleroderma and other autoimmune diseases. 300 Because of the high costs, however, many patients cannot be treated with extracorporeal photopheresis.…”

Section: European Research Contributionsmentioning

confidence: 99%

The European Hematology Association Roadmap for European Hematology Research: a consensus document

et al. 2016

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T he European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

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“…A meta-analysis based on nine relevant prospective studies showed a pooled overall response rate of 0.69 (skin 0.84, gut 0.65, liver 0.65) [37]. A Recent review reports similar results in response with an impact of ECP response on overall survival in multivariate analysis that is much more meaningful for clinical practice [39]. We also have to consider that the complexity of using and evaluating ECP in aGVHD is related to the delayed onset of ECP, delayed action and the necessity of combined immunosuppression.…”

Section: Graft Versus Host Disease: More In Chronic Than In Acute Gvhd?mentioning

confidence: 53%

Extracorporeal Photopheresis: Scientific and Technical Considerations for Improving Clinical Management of Patients

Garban¹,

Makowski

Carras

et al. 2014

J Stem Cell Res Ther

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Extracorporeal photopheresis for treatment of adults and children with acute GVHD: UK consensus statement and review of published literature

Cited by 42 publications

References 36 publications

Treatment of Pediatric Acute Graft-versus-Host Disease—Lessons from Primary Immunodeficiency?

Treatment of Pediatric Acute Graft-versus-Host Disease—Lessons from Primary Immunodeficiency?

The European Hematology Association Roadmap for European Hematology Research: a consensus document

Extracorporeal Photopheresis: Scientific and Technical Considerations for Improving Clinical Management of Patients

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