Extracorporeal photopheresis (ECP), also known as extracorporeal photochemotherapy, is a safe immune modulating treatment used to treat an increasing number of conditions. Originally used to treat Sézary syndrome, a leukaemic form of primary cutaneous T-cell lymphoma (CTCL), its use has now expanded to include acute and chronic graft-versus-host disease (GvHD) and other conditions.
There are about 200 ECP units around the world. Treatment protocols vary and optimal treatment protocols still need to be established.
What is ECP?
ECP uses either a closed system, where the device performs the entire procedure, or separate devices for each step. Anticoagulation with heparin or citrate prevents clotting within the tubing system.
Treatment is often undertaken on two consecutive days each month. Response to treatment is assessed at 3-monthly intervals. ECP is discontinued at 6 months if the response not adequate. The process involves 3 steps and takes about 2 to 4 hours to complete.
Step 1: Leukaphoresis
This involves drawing the patient’s blood, followed by centrifugation to separate and collect the white blood cells (leukocytes).
Step 2: Photoactivation
The collected white cells are mixed with methoxypsoralen (see PUVA), which makes the T-lymphocyte cells sensitive to ultraviolet A (UVA) radiation. They are then exposed to UVA, which damages diseased cells.
Step 3: Re-infusion
The treated white cells are re-infused back into the patient.
How does it work?
The mechanism of action of ECP is not completely understood. Theories on how it may work are:
- The combination of psoralen and UVA radiation causes apoptosis (“programmed cell death”) of affected T cells.
- When returned to the body, the damaged white cells trigger the immune system to recognise antigens on the T cells.
- Less damaged monocytes consume (phagocytose) the apoptotic T cells, a normal anti-tumour response.
- More exposed monocytes develop into dendritic cells that instead dampen the immune response.[1,2]
What are the clinical applications for ECP?
Cutaneous T-cell lymphoma (CTCL)
CTCL was the first approved indication for ECP.
ECP is a first-line treatment for the erythrodermic and leukaemic form of CTCL, Sézary syndrome. Without treatment, Sézary syndrome has a poor prognosis with a median survival of 4 years. The published overall response rate to ECP is about 43% with a complete response of 10%. The results depend on many factors including treatment protocol.
ECP may also be used in mycosis fungoides, particularly advanced (Stage III) or erythrodermic disease.
Graft versus host disease (GvHD)
Acute and chronic forms of GvHD are potentially severe complications of allogeneic stem cell haematopoietic transplants. First-line treatment is with systemic corticosteroids.
ECP may be considered in the approximately 50% of patients with acute GvHD that do not respond to corticosteroids. ECP has been most successful when started early. The skin has similar response rates to other affected organs. Complete response rate is about 80% when the skin alone is affected and 60% when there is also liver or gastrointestinal involvement. Higher response rates are reported with more frequent treatments.
ECP is a second-line treatment for chronic GvHD. It is used in patients refractory or intolerant of corticosteroids. ECP appears not to interfere with the anti-leukemic effect of grafted cells. The risk of infection is also less than with other immunosuppressive treatments.
When used early in systemic sclerosis, ECP has been reported to reduce dermal thickness. Internal organ involvement is not helped.
Other uses for ECP
ECP has been reported of benefit in some patients with:
- Crohn disease 
- Solid organ transplant rejection, particularly heart 
- Systemic lupus erythematosus 
- Atopic dermatitis 
- Pemphigus 
- Type 1 diabetes 
- nephrogenic fibrosing dermopathy
What are the possible side effects of ECP?
ECP is well tolerated and it does not increase the risks of infection. Side effects are uncommon and mild. These include:
- Transient drop in blood pressure, causing dizziness during leukaphoresis
- Temporary low-grade fever 2-12 hours after treatment
- Increased skin redness or itchiness 6-8 hours after treatment
- Possibly some light sensitivity following treatment
- Reduced platelet count (thrombocytopenia) and red cell count (anaemia)
During the procedure the medical team should keep a careful watch on the patient’s blood pressure and blood count. Occasionally saline may be given to maintain blood pressure.
Patients taking medications to reduce blood pressure should be advised to not take these until after the ECP procedure. Patients with hypertriglyceridemia should be advised to fast before the procedure, as treatment is less effective with high circulating lipid-rich blood.
Challenges of ECP
Challenges include the availability of ECP, good venous access, anticoagulation, low blood count (haematocrit) and cost. Optimal treatment protocols still need to be established.