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Extracorporeal photopheresis versus alternative treatment for chronic graft‐versus‐host disease after haematopoietic stem cell transplantation in paediatric patients

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Abstract

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Background

Chronic graft‐versus‐host disease (GvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation occurring in 6% to 65% of the recipients. Currently, the therapeutic mainstay for chronic GvHD are corticosteroids that are frequently combined with other immunosuppressive agents in people with steroid‐refractory manifestations. There is no established standard treatment for steroid‐refractory chronic GvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8‐methoxypsoralen, ultraviolet radiation and re‐infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is an updated version of a Cochrane review first published in 2014.

Objectives

To evaluate the effectiveness and safety of ECP for the management of chronic GvHD in children and adolescents after haematopoietic stem cell transplantation.

Search methods

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

Selection criteria

Randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in paediatric patients with chronic GvHD after haematopoietic stem cell transplantation.

Data collection and analysis

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

Main results

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

Authors' conclusions

The efficacy of ECP in the treatment of chronic GvHD in paediatric patients after haematopoietic stem cell transplantation based on RCTs cannot be evaluated since the original version of this review and the first review update found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this patient population will be challenging due to the limited number of patients, the variable disease presentation and the lack of well‐defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, patients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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Extracorporeal photopheresis treatment for chronic graft‐versus‐host disease after haematopoietic stem cell transplantation in paediatric patients

Background

Chronic 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 others. These immune reactions may cause acute inflammation (sudden swelling) followed by chronic (long‐term) changes of 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) in the form of corticosteroids in combination with other immunosuppressive agents in refractory cases (where the disease is resistant to treatment). These drugs are supposed to suppress the immune‐mediated attack of the patient's cells. Limited effectiveness and severe side effects of these 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 patient's body. These immune cells are 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 chronic graft‐versus‐host disease.

Study characteristics

We searched scientific databases for randomised controlled trials (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 chronic graft‐versus‐host disease in children and adolescents (under 18 years of age) after HSCT.

Results

The original version of this review and this 2015 review update found no RCTs that analysed the efficacy of ECP for paediatric patients with chronic 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. Thus, ideally, ECP should be applied in paediatric patients in the context of RCTs only. ECP may be considered in people with steroid‐refractory chronic GvHD, keeping in mind that such a treatment is not supported by high‐level evidence. If treatment decisions based on clinical data in favour of ECP are made, patients should be carefully monitored for beneficial and harmful effects and efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP.