Background
Acute graft-versus-host disease is a common complication after haematopoietic stem cell transplantation (HSCT; transplant of blood-forming stem cells). Immune cells (white blood cells) from the donor recognise the recipient's cells as foreign ('non-self'). Therefore, the transplanted immune cells attack the cells of the recipient. The main affected organs are skin, liver and gut among other organ tissues. These immune reactions may cause acute inflammation (sudden swelling) followed by chronic (long-term) changes of the organs (e.g. fibrosis; scarring of the lungs). First-line therapy usually consists of immunosuppressive drugs (which reduce the strength of the body's immune system) such as corticosteroids in combination with other immunosuppressive agents in refractory cases (where the disease is resistant to treatment). The use of these immunosuppressive drugs is designed to suppress the immune-mediated attack of the recipient's cells. Limited effectiveness and severe side effects of these immunosuppressive drugs have led to the application of several alternative approaches.
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that involves collection of immune cells from peripheral blood outside the person's body. These immune cells are then exposed to a photoactive agent (a chemical that responds to exposure to light; e.g. 8-methoxypsoralen) with subsequent ultraviolet-A radiation and then reinfused. The immunomodulatory effects of this procedure are not completely understood.
Several current clinical practice recommendations suggest consideration of ECP in children and adolescents with acute graft-versus-host disease after HSCT.
Study characteristics
We searched scientific databases for randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) that were designed to evaluate the effectiveness and safety of ECP for the management of acute graft-versus-host disease in children and adolescents (under 18 years of age) after HSCT.
Results
The original version of this review and both the first and second review update did not find any RCTs investigating the efficacy of ECP in children and adolescents with acute graft-versus-host disease after HSCT. Current recommendations are based on retrospective studies (where outcomes occurred to the participants before the study began) or observational studies (where investigators did not intervene, and simply observed the course of events) only. We recommend the use of ECP in children and adolescents after HSCT only in the context of RCTs.
The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions.
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015.
To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT.
We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE (PubMed) and Embase (Ovid) databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
We sought to include randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in children and adolescents with aGvHD after HSCT.
Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author.
We identified no additional studies in the 2021 review update, so there are still no studies that meet the criteria for inclusion in this review.