Thursday 22 August 2013

Do I need ECP?

For the last six weeks, the question of whether I need Extracorporeal Photopheresis (ECP) has been discussed at several of my hospital appointments, and, in that time, four different doctors have offered one-of-three different opinions: Two doctors thought yes, one thought it was worth having one last attempt at tapering-off the steroids (now that I'm also on Ciclosporin), and one thought that the other opinions are perfectly valid and I should just pick one, i.e. sat on the fence. In other words, after speaking to those in the know, the only thing that was actually clear was that it's not really clear at all.

So, what did I do? I hear you say. Well, two weeks after being referred for ECP, the doctor that I saw on the 23rd of July (day +173) decided to try reducing my steroid (Prednisolone) dose from 30mg/day to 20mg/day, whilst I waited for my appointment to discuss ECP with the team in Rotherham a week later; I think we both suspected that I'd get away with that dose of Prednisolone, now that I was also on Ciclosporin, and I was happy to give it a try, as I didn't want to be taking any more than necessary.

Note: On the same day, a CT scan was arranged for the 29th of July (day +179) to ensure that everything was still fine from a Hodgkin's Lymphoma perspective, and I found out that the latest skin biopsy was also inconclusive about the presence of GVHD; It would have been nice if the skin biopsy had confirmed GVHD, but it didn't matter, as there wasn't really any doubt about it. (I'd also had another chimerism test, two weeks prior, when I had the skin biopsy, and that showed I was still 98% donor.)

After a week on the reduced steroid dose, my skin wasn't any worse (it was still quite dry in places though) and it was time to see the ECP team in Rotherham. The doctor and nurses that I saw in Rotherham explained a bit about the treatment, showed me around the facilities, asked about my medical history, examined my skin, and took yet more blood samples; I'm sometimes surprised that there's any blood left to take!

Note: I was a bit disappointed that I didn't learn more about the treatment etc when visiting the ECP team in Rotherham, but now that I think about it I had already read quite a lot about it on the Internet, so realistically there wasn't that much left to add.

After meeting the ECP team in Rotherham, I realised that they were hoping I'd let them know within a couple of days or so whether I wanted to start the treatment or not, but I explained that I'd just had a CT scan (the day previously) and thought it would be best to discuss the results of that at my next appointment in Sheffield a week later, i.e. the 6th of August (day +187), before making any decisions about having ECP.

A week later, I discussed my latest CT scan results with a doctor in Sheffield, and it seemed that there was some concern about them, as they highlighted a mass in my chest that measured roughly 7cm by 5cm by 2cm, which is obviously a reasonable size, hence I maybe needed a PET-CT scan to see whether that mass was active disease or just scar tissue. I say "maybe", as because all of my prior scans had been done at another hospital, which this hospital couldn't access without first requesting them, it wasn't really possible to interpret the latest CT scan results, as they couldn't compare them with that of my prior scans. Fortunately, two days later, once the prior scans were available, I learnt that my latest CT scan was actually an improvement.

The doctor with which I initially discussed the latest CT scan results was also the same doctor that was in favour of having one last attempt at tapering-off the steroids, hence it's perhaps no surprise that I took that path in the end; If the disease had been active, then reducing the immune suppression would have given the immune system a better chance at fighting it. The plan was to drop the steroid dose down to 10mg/day for five days and then to stop it altogether, as long as everything went smoothly.

Fortunately, it seems that being on the Ciclosporin has meant that stopping the steroids hasn't resulted in the skin GVHD flaring-up to the same extent as previously. My skin has become quite dry and slightly red again in numerous places, and there are some patches that feel a bit burnt, but it's not too bad so far. Below, you can see a photo (click to view full size) of one of my hands before (on the left) and after (on the right) taking a shower; They give an idea of how the heat affects the skin GVHD.

Skin GVHD - Hand Before Shower
Skin GVHD - Hand After Shower

For the time being, with the skin GVHD being how it is, I can continue without any steroids, but need to stay on the same dose of Ciclosporin, until my next appointment in Sheffield on the 3rd of September (day +215) when it will be reviewed. Thankfully, perhaps due to stopping the steroids, I seem to be pretty much symptom free of the two viral infections that I've been battling with in recent months, even though the latest mouth swabs on the 15th and 29th of July (days +165 and +179) were still positive.

Note: I was admitted to my local hospital on the 14th of August (day +195), due to waking-up with quite bad pain in my knees (I could hardly walk) and a high temperature (38.3°C), but bizarrely those symptoms disappeared (without any medications) quite quickly; i.e. in the hour or so that it took to organise everything and get to the hospital, everything was back to normal. I was discharged a little over twenty-four hours later, after various blood tests etc had failed to highlight anything of any real concern.

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.