Extracorporeal photopheresis for acute graft-versus-host disease after haematopoietic stem cell transplantation in paediatric patients


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 patient's cells as foreign ('non-self'). Therefore, the transplanted immune cells attack the cells of the patient. 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 patient'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 re-infused. The immunomodulatory effects of this procedure have not been completely elucidated.

Several current clinical practice recommendations suggest consideration of ECP in paediatric patients 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.


The original version of this review and the first review update found no RCTs that analysed the efficacy of ECP for paediatric patients with acute graft-versus-host disease after HSCT. Current recommendations are based on retrospective (a study in which the outcomes have occurred to the participants before the study began) or observational (a study in which the investigators do not seek to intervene, and simply observed the course of events) studies only. We recommend the use of ECP in paediatric patients after HSCT only in the context of RCTs.

Authors' conclusions: 

The efficacy of ECP in the treatment of aGvHD in paediatric patients after HSCT is unknown and its use should be restricted 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 2015 review update brought about no additions to these conclusions.


Read the full abstract...

Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT) occurring in 8% to 59% of the recipients. Currently, the therapeutic mainstay for aGvHD is 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 re-infusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is an updated version of a Cochrane review first published in 2014.


To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT.

Search strategy: 

We searched the Cochrane Register of Controlled Trials (CENTRAL) (Issue 9, 2015), MEDLINE (PubMed) and EMBASE (Ovid) databases from their inception to 23 September 2015. We searched the reference lists of potentially relevant studies without any language restrictions. We searched eight trial registers and four conference proceedings on 29 September 2015.

Selection criteria: 

Randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in paediatric patients with aGvHD after HSCT.

Data collection and analysis: 

Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author.

Main results: 

We identified no additional studies in the 2015 review update, in total leading to no studies meeting the criteria for inclusion in this review.