Extracorporeal photopheresis, 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, its use has now expanded to include acute and chronic graft-versus-host disease and other conditions.
There are about 200 extracorporeal photopheresis units around the world. Treatment protocols vary and optimal treatment protocols still need to be established.
What is extracorporeal photopheresis?
Extracorporeal photopheresis uses either a closed system (where the device performs the entire procedure) or uses 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. Extracorporeal photopheresis 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: Leukapheresis
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 extracorporeal photopheresis work?
The mechanism of action of extracorporeal photopheresis is not completely understood. Theories on how it may work are:
- The combination of psoralen and UVA radiation causes apoptosis (programmed cell death) of some of the affected T cells.
- When returned to the body, the damaged white cells trigger the immune system to recognise antigens on the T cells and destroy them.
- Less damaged monocytes phagocytose the apoptotic T cells, which is a normal anti-tumour response.
- Monocytes exposed to the radiation develop into dendritic cells that dampen the immune response [1,2].
What are the clinical applications for extracorporeal photopheresis?
Cutaneous T-cell lymphoma
Cutaneous T-cell lymphoma was the first approved indication for extracorporeal photopheresis.
Extracorporeal photopheresis is a first-line treatment for the erythrodermic and leukaemic form of cutaneous T-cell lymphoma, Sézary syndrome. Without treatment, Sézary syndrome has a poor prognosis with a median survival of 4 years. The published overall response rate to extracorporeal photopheresis is about 43% with a complete response of 10%. The results depend on many factors including the treatment protocol.
Extracorporeal photopheresis may also be used in mycosis fungoides, particularly advanced (Stage III) or erythrodermic disease.
Acute and chronic forms of graft-versus-host disease are potentially severe complications of allogeneic stem cell haematopoietic transplants. First-line treatment is with systemic corticosteroids.
Extracorporeal photopheresis may be considered in the approximately 50% of patients with acute graft-versus-host disease that do not respond to corticosteroids. Extracorporeal photopheresis has been most successful when started early. The skin has similar response rates to other affected organs. The 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.
Extracorporeal photopheresis is a second-line treatment for chronic graft-versus-host disease. It is used in patients refractory or intolerant of corticosteroids. Extracorporeal photopheresis 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, extracorporeal photopheresis has been reported to reduce dermal thickness. Internal organ involvement is not helped.
Other uses for extracorporeal photopheresis
Extracorporeal photopheresis 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 extracorporeal photopheresis?
Extracorporeal photopheresis 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 leukapheresis
- 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
- Thrombocytopenia and 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 the blood pressure.
Patients taking medications to reduce blood pressure should be advised to not take these until after the extracorporeal photopheresis 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 extracorporeal photopheresis
Challenges include the availability of extracorporeal photopheresis, good venous access, anticoagulation, low haematocrit and the cost of the treatment. Optimal treatment protocols still need to be established.