Friday 9 August 2013

What is Extracorporeal Photopheresis (ECP)?

Extracorporeal Photopheresis (ECP) is a type of therapy that is primarily used in the treatment of Graft Versus Host Disease (GVHD) and Cutaneous T-Cell Lymphomas (CTCLs). For GVHD, ECP is a second-line therapy, which is used far more commonly to treat the chronic rather than acute form, whereas for CTCLs, such as Mycosis Fungoides (MF) and S├ęzary Syndrome (SS), it is potentially a first-line therapy.

How does it work?

ECP is a simple treatment to describe, as it essentially just involves connecting-up the patient to a machine that extracts the white blood cells from their blood, so that they can be: mixed with a drug known as UVADEX (Methoxsalen), exposed to UV light, and returned to the patient; The UVADEX makes the white blood cells sensitive to UV light, so that when they're exposed to it, the result is that (over several days) those cells eventually die off, due to becoming incapable of normal growth and development.

Note: You can deduce much of what is involved with ECP from the term itself, as "extracorporeal" means outside of the body, "photo" is referring to light, and "pheresis" is the process of: drawing blood from a patient; followed by separating that blood into its components in order to isolate those of interest (e.g. for extraction or treatment); before finally returning the remaining blood components back to the patient.

The science behind how exactly ECP works is not yet fully understood, but one theory is that the immune system recognises that the lymphocytes (more specifically the T-cells) amongst the white blood cells are dying off, as a result of the UVADEX making them more sensitive to the UVA light (the long wavelength form of UV light) to which they were exposed, and consequently it produces healthy ones to replace them.

What is it like?

There are different machines available to perform the ECP treatment, but having had a tour around the facilities at Rotherham General Hospital, it would seem likely that I would be treated with the CELLEX System manufactured by Therakos, i.e. their latest generation machine that offers a number of advantages over their earlier UVAR XTS System. Each treatment session takes about three hours on the UVAR XTS System, but that has been halved with the CELLEX System; Although, the duration can vary by roughly half an hour with the latter, depending on whether a single cannula/line is used for both the extracting and returning of blood, or whether a separate one is used for each. Also, whilst the CELLEX System only requires up to about a pint of the patient's blood to be out of their body during treatment, i.e. less than that with the UVAR XTS System, the CELLEX System can be primed with compatible red blood cells from a donor too, thereby allowing younger/smaller patients to be treated; unlike with other patients, the young/small can't cope with a pint of their blood being out of their body.

The side effects from ECP tend to be minor and short-lived (only lasting a day or so), and include: sensitivity to sunlight, fatigue, itching, a mild fever, and a slight reddening of the skin. For the sensitivity to sunlight, even on a cloudy day, high factor suncream and protective sunglasses should be worn afterwards (for a day) to prevent severe sunburn and cataracts, respectively, as both direct and indirect exposure to sunlight can prove problematic. The mild fever and slight reddening of the skin tends to appear about six to eight hours after the treatment, and can be safely ignored, i.e. it's only if they are more severe, e.g. if the skin becomes sore or starts to peel or blister, that action needs to be taken. It is also possible to feel dizzy/faint during the treatment itself, due to a drop in blood pressure, as a result of the machine drawing blood.

What is involved?

For patients with GVHD, numerous ECP treatments are required over several months, where each is split into two identical sessions on consecutive days, and whilst the exact number and frequency of the treatments varies based on the patient's response, the most optimistic scenario is for fortnightly treatments for the first fourteen weeks, followed by a further three treatments, each four weeks apart, and then finally tapering-off/stopping the treatments altogether. However, if the GVHD doesn't respond as well to the treatments as hoped, then the treatments may remain more frequent for longer and be greater in number, and if the treatments prove to be ineffective, then they will stop sooner. In some cases, the treatments can continue for more than two years.

Note: It has been estimated that the first year of ECP treatment could cost between nearly £35,000 and £90,000, depending on the number and frequency of treatments that are needed. However, it is expected that £45,000 is a more realistic figure.

It takes a few ECP treatments before the process can start to work, and consequently the patient's steroid (e.g. Prednisolone) and/or immune suppressant (e.g. Ciclosporin) dose can be reduced, in order to see whether the patient is responding, and if so how well. In the ideal scenario, the patient will be gradually tapered-off any steroids and/or immune suppressants, thereby allowing their immune system to restore itself back to its normal level, and the patient to be no longer at greater risk of infection; ECP not suppressing the immune system is one of the advantages of this treatment.

In the days running up to each ECP treatment, there is some preparation that is necessary: blood tests need to be performed, so that if the patient's hemoglobin level is below 10g/dL and/or their platelet count is below 20x109/L, the necessary blood transfusions can be arranged; for 48 hours prior, plenty of fluids (no caffeine/alcohol) are drank, so that the patient is well hydrated; and for 24 hours prior, only low-fat (no meat, fried-food, cheese, eggs, butter and dessert) is eaten, so that the patient's blood is easily separated by the machine. It is also advisable to avoid limes, figs, parsley, parsnips, mustard, carrots and celery, as they can increase skin sensitivity.

Note: Whilst not an issue for myself, pregnancy should also be avoided when having ECP treatment, as studies with animals has shown that the drug used to sensitise the white blood cells to UV light can also result in birth defects and death of the fetus.

How well does it work?

Rotherham General Hospital recently performed a retrospective analysis of two hundred and nineteen patients that they treated for chronic GVHD between 1996 and 2012, and that showed that ECP is most effective for GVHD of the skin, followed by mouth, gut, liver, eyes and lungs, as (at least partial) response rates of about 70%, 65%, 55%, 50%, 40% and 15% were seen, respectively. Also, indicators of poorer outcomes were starting treatment with a high steroid dose (greater than 0.5mg/kg), low platelet count (less than 100x109/L) and high Bilirubin level (greater than 2mg/dL).

Note: As you'd likely expect, ECP response rates tend to be better amongst patients with lower grade GVHD and with fewer organs involved, hence for patients like myself, i.e. with only grade two GVHD of the skin, the ECP response rates are quite high.

1 comment:

  1. Hiya,
    I first caught 'MCL' in 2007, after treatment and quite a lot of infections later, I remained mainly clear until last year 2012 when I caught Leukemia, signed my life away, more treatment, and I beat that away - but - it apparently would come back unless I had an SCT. A 100/100 donor was found and on August 10th 2012 I had the Treatment, again signing my life away. Just before the leukemia treatment I got married to to girl I have been with for over 27 years (well I was given around 4 weeks and nobody thought I would get past all the treatment stages)
    I have been fighting Skin GVHD at least since March this year when I refurnished a lot of the house (amazing what you can buy if you look hard on eBay) - (talk about red sore hands though from all the 'Pick-ups' I could have lit-up a dark room)
    I had and still have - although it looks TO ME as if it is getting slowly better - reddening around the tips of my fingers, palms of my hands and face. A good few weeks ago I also found it hard to swallow - sometimes food, other times fluids, but never both.
    Naturally my Consultant, the brilliant Dr Adrian Bloor at the 'Christie Hospital, Manchester' put me on a high dose of 'Steroids' 100mg to start - now down to 15mg daily.
    'The 'ECP' treatment had been talked about until today. Then I got a phone call from the 'Christie', they can see me next Monday for a full explanation of whats to come and when I start my treatment.
    I know most things to do with my past treatments - even keeping a spread sheet of my blood results since 2007 - but I have to say, Your blog is fantastically informative for me.
    Thanks and I hope you get better soon.
    Marcus (now 59)