Monday 27 August 2012

What is the antibody treatment?

Today marks three weeks since I was informed my Hodgkin's Lymphoma is refractory (no longer responding to chemotherapy) and that my last chance for a cure is an antibody treatment that is not yet approved for general use on the NHS, i.e. requires special approval due to the costs etc involved.  As you can probably imagine, the idea of whether I receive the antibody treatment potentially coming down to NHS budgets is not the most comfortable one, and when it was explained it could take up to three weeks for a decision to be made, it did cross my mind that they might seem like long weeks.

As luck (or not) would have it, today is actually a bank holiday Monday, so although three weeks have passed now I'm still waiting to find out the decision; A nurse I spoke to on Friday afternoon told me that the panel were scheduled to make their decision on a conference call later that day, and that in all likelihood I would find out on Tuesday.  The doctor that had been fielding questions for the panel over the last couple of weeks or so seemed quietly optimistic that the antibody treatment would be approved though, but obviously couldn't make any promises, so I'm kind of assuming all will be well.

To be honest, the three weeks of waiting have passed pretty quickly really, and it's not even been on my mind that much.  I did spend a few hours reading about the antibody treatment in the first few days (a nurse looking after my case provided some materials, and I did some further research online), but after that I pretty much forgot about it.  Although I've been signed-off work since starting the treatment for my latest cancer relapse, I've not really ever struggled with filling my time, so have rarely found myself contemplating (let alone worrying about) what the future may hold; Granted I've spent a fair bit of that time in hospital, and/or feeling naff, but it is funny how quickly you can get used to not working, not to mention find yourself thinking how/why did I ever fit in a full-time job!

So, what is the antibody treatment, I hear you say?  Well, the one that I will hopefully be starting soon is called Brentuximab Vedotin.  There are a few different categories of antibody treatments, each of which work in different ways, but this one essentially locks-on to cells that it recognises as cancer, and then delivers those cells some chemotherapy right to their door!  I suppose in that sense such antibody treatments are a bit like a courier service for chemotherapy, which continuing the analogy makes traditional chemotherapy a bit like the leaflets we all get posted through our doors, i.e. for some those leaflets are useful, but for others they are just an annoyance we could do without!

In case you are curious, some antibody treatments use radiation instead of chemotherapy to kill the cancer, i.e. they lock-on in the same way, but have radioactive isotopes attached to them, and hence are really an especially targeted form of radiotherapy.  The other two categories of antibody treatments take slightly different approaches though: The first essentially paints a target on the cancer cells, by simply locking-on to them, so that the patient's own immune system can then recognise them as cancerous and kill them off, and the second locks-on to the cancer cells in such a way as to prevent them from receiving their normal signal to divide/grow, thereby kind of starving the cancer.

As you might imagine, one of the tricky parts of developing the various antibody treatments is that ideally such drugs need to lock-on to only the cancerous cells.  However, whilst the ideal solution involves finding something unique about the cancerous cells that is not found in normal cells, settling for something that is nearly unique can work too.  The key to the nearly unique scenario is finding something that is much more targeted than traditional chemotherapy, as it just attacks fast dividing cells, and from which the body can easily recover, i.e. repair any damage caused by friendly-fire.

Perhaps not surprisingly, the various types of cancer tend to have different characteristics, and consequently that means when developing antibody treatments it can be necessary to design drugs on an almost type of cancer specific basis.  Due to the complexity of some of these drugs, it can take a long time to develop them, hence that combined with their potential specificity has implications in terms of cost, as well as for what types of cancer there are currently antibody treatments available.

In the case of Brentuximab Vedotin, it works by targeting a protein/receptor known as CD30, which is found on most of the cells in Hodgkin's Lymphoma (as well as Anaplastic Large Cell Lymphoma).  In a clinical trial of this antibody treatment, conducted in 2010, a third of the patients suffering from relapsed and/or refractory Hodgkin's Lymphoma achieved complete remission (no signs of the disease), another forty percent achieved partial remission (at least a fifty percent reduction in the disease), and a further twenty percent achieved at least some measurable reduction in the disease.  It would seem that it was these results that led to the drug quickly being approved for use in the U.S. and Europe, and it currently being available on a compassionate use/named patient basis in the NHS.

For myself, the Brentuximab Vedotin is just intended to reduce the Hodgkin's Lymphoma by enough to enable me to have an Allogeneic (from a donor) Stem Cell Transplant, in the hope that the two types of treatment combined will finally form the cure for my disease.  Consequently, that means I don't need to achieve complete remission from the antibody treatment, but I do need to have a significant response to it, so that the stem cell transplant stands a chance of working.  In other words, the idea is that what the antibody treatment doesn't get itself, and is still around after the chemotherapy (and perhaps total body irradiation) given as part of the stem cell transplant, will be mopped-up by the new immune system I have afterwards; the new immune system being thanks to the generous gift provided by my (yet to be identified) compatible stem cell (or bone marrow) donor!

When the antibody treatment was first suggested to me, given the failed attempt with chemotherapy, and I asked about the percentage cure rates, the doctor seemed to kind of give mixed impressions about the prognosis, as whilst the treatment plan itself sounded better there were clear suggestions that the reality may not be so positive.  However, after reading about the results of the clinical trials of Brentuximab Vedotin, I felt much more positive about it all really (justified or not!).  It may be an odd thing to say, but at this point odds roughly equivalent to flipping a coin don't seem so bad to me!

Saturday 25 August 2012

How can I donate stem cells or bone marrow?

Since my latest relapse of Hodgkin's Lymphoma, and the doctors informing me that my treatment plan involves an Allogeneic (from a donor) Stem Cell Transplant, a few people have asked me about how they could donate stem cells (or bone marrow), so if you are interested in becoming a donor and would like to find out more information, or you are just curious about what is involved, then read on!

Before I explain the donation process itself, I should probably provide a little background on where stem cells (and bone marrow) are located in your body and what they actually do.  Bone marrow is the flexible tissue found in the centre of all of your large bones, and is where stem cells are produced.  Stem cells develop into either: white cells to fight infection; red cells to carry oxygen to and remove waste from organs and tissues in your body; or platelets to stop bleeding (e.g. if you cut yourself).  Should you donate stem cells (or bone marrow), then a sufficient amount is collected (by methods explained later), and much like with blood donations your levels soon return back to normal.

When a patient is in need of an Allogeneic Stem Cell Transplant, finding a suitable donor is one of the very first steps, and this involves tissue typing.  Tissue typing is the name given to the process of matching the patient to the donor; This is necessary as in all likelihood two randomly chosen people are extremely unlikely to be compatible for transplantation.  With Allogeneic Stem Cell Transplants, only about three in every ten patients find a match amongst their family, and for the remaining patients it is necessary to search the various donor registers for a match.  Countries around the world maintain their own donor registers, but they collaborate to find matches, hence whilst searches will likely start with donor registers close to home, it may prove necessary to search world-wide to find a particular patient a suitable match, as some patients have rare tissue types.

Note: My sister was tested to see whether she was a match for me, which she was not, but that was probably a good thing, as I'm not sure whether I could have afforded her quoted price per stem cell!

Whilst not everyone can register as a potential donor (factors such as age, health and medical history need to be taken into account), a lot of people can do.  For the majority of people that do register, they never go on to be an actual donor, as a patient requiring their tissue type is never encountered.  However, donors have been known to donate more than once, at their own discretion of course.

In the UK, you can join one of three registers, and they are operated by the Anthony Nolan charity, NHS and Welsh Blood Service.  For simplicity I will focus on the Anthony Nolan charity, as it doesn't also require you to be a blood donor; However, you may wish to consider the other registers, for reasons such as the different age restrictions.  The registration process for the Anthony Nolan charity involves a fairly short medical questionnaire that will probably take you around about ten minutes to complete.  After successfully completing the questionnaire, you will be sent a saliva test kit, which once returned can be used to determine your tissue type and record the results (along with your details) on the register.  You do have to be aged between 16 and 30 to register, and you need to pass the medical exclusion criteria.  There are no costs involved to yourself, and should you ever become an actual donor, any travel and hotel arrangements will also be made for you.

Note: The saliva test kit enables preliminary matching, and should you appear to be a match for a patient, it will be necessary for some blood tests to take place to ensure that you are definitely a match, and that you are a healthy donor, e.g. you won't pass any infections on to the patient.

When it comes to the process of donating itself, there are two methods available: The first of the methods is a bone marrow harvest, and the second is a peripheral blood stem cell collection.  The first tends to be favoured for donating to younger children, and clinical trials have suggested that it results in a slightly lower probability of the patient developing chronic graft versus host disease (cGVHD); GVHD is where the donor's stem cells (or bone marrow) produces white cells that attack some of the patient's organs and tissues, due to it incorrectly identifying them as damaged, foreign or an infection.  The second is the least invasive of the methods, is by far the most commonly used, has the advantage of the patient recovering from the transplantation quicker (typically by a few days), and clinical trials have suggested that it results in a lower risk of the transplant failing to take.

The bone marrow harvest method, which is the most invasive of the two, involves the donor going into theatre, having a general anaesthetic, and finally a large needle being inserted into their hip bone (in the lower back) in order to extract sufficient bone marrow.  The general anaesthetic will avoid any pain being felt during the procedure, but once it wears-off some discomfort may be noticed for a few days, which can be masked by taking some paracetamol, if the donor feels the need.  Having had a few bone marrow biopsies myself during the course of my treatment, which involves a very similar procedure, my personal experience is that the discomfort is easily tolerated without painkillers.  Either way, this method involves a two-night stay in hospital, just for observation purposes after the general anaesthetic, hence you will be well looked after, before finally returning to your normal life; You may wish to have a few extra recovery days though to fully recuperate from the procedure.

The peripheral blood stem cell collection method, which is the least invasive of the two, involves a two step process: The first step requires having an injection in the stomach for a few days (each administered by a nurse at your home or office), so that the stem cells are encouraged to migrate out of the bone marrow into the blood stream, thus allowing them to be collected in the second step.  The second step involves having a small cannula inserted into both arms, one for extracting the blood, and another for returning it; Inbetween the blood will go through a machine that will filter-out the stem cells, so that they can eventually be donated to the patient.  The daily injections are similar to having a vaccination, i.e. you hardly feel anything, but they can cause some bone/joint/lower back pain that without taking paracetamol can be quite painful.  Having experienced this myself on a few occasions (when taking a single concentrated dose, rather than the lower daily doses), I know how much it can hurt, but the good news is that paracetamol is amazingly effective at masking the pain, so if you do start to feel any slight discomfort from them, you can be confident that you will be fine if you take some paracetamol.  The filtering of the stem cells is an uneventful process, which takes around four hours or so to complete, during which time you can just sit and read or something, as you won't feel a thing.  It is sometimes necessary for the donor to go through the filtering process a couple of times (once per day), as sufficient stem cells are not collected on the first attempt.  When I went through the process myself, more than enough were collected in one session, which I believe tends to be the case (especially for younger males), so it was all over and done with pretty quickly really.  Once the filtering is complete, you are free to return to your normal life; You will likely feel fine, as the side effects from the injections wear-off pretty quickly, i.e. typically within about twenty-four hours.

Note: For both methods, the donors on the Anthony Nolan register will have the in-hospital procedures at a specialist collection centre, usually in London.

Which ever method is chosen, you will likely come out of it thinking that was much easier than I expected, as neither are anything to worry about.  Even better still, you will probably be feeling proud of yourself for donating your stem cells (or bone marrow), and potentially saving someone's life!

Monday 6 August 2012

Chemo out, Antibody in!

It was ten days and nights after the latest infection before I finally got to go home; My blood counts were still pretty low at the time, but given I'd not been on any antibiotics for a couple of days and I still felt fine then I was allowed to go home anyway - I just had to return in a few days for a blood test.  I went home with what seemed like enough drugs to start my own eBay store, but it was mostly just a few months worth of the usual suspects (anti-bacterial, anti-fungal and anti-viral).  I was also given some Filgrastim (G-CSF) injections, in order to boost my immune system; After a day or two I could tell that they were working, as I had some lower back pain and a kind of headache (bizarrely, it is at the back of the head, just above the neck).

After a few days, I went for the blood test, and at the same time got the hickman line flushed and had the connectors changed too.  The blood test results were fine, and showed the Filgrastim (G-CSF) injections had definitely kicked my bone marrow into action, as my neutrophils level was pretty high now (more than double the top-end of the normal range), so I could stop administering those injections.  The results for my recent PET scan were also back now, but unfortunately they were not good, as they showed that the disease was not responding to the IVE chemotherapy, so there was little point in continuing with that treatment.

The results of the PET scan kind of blind-sided me a little, as I wasn't expecting to get them for another few days, and I had also (to some extent) assumed that they would be fine, as the fluid that had gradually built-up around my heart and right lung before I started treatment (presumably as a side effect of the cancer) had either not reappeared after being drained or drained by itself once I started treatment, so I'd taken those as signs that the IVE chemotherapy was working; I'll most likely ask for an explanation when I get chance.

One of the doctors explained that given the IVE chemotherapy wasn't working then a potential alternative is an antibody treatment.  An antibody treatment is quite different to chemotherapy - Both in terms of how it works and the processes involved in using it in the NHS.  Unlike chemotherapy, which just indiscriminately attacks fast dividing cells (some of which are the cancer, but others are not), an antibody treatment is a much more modern/targeted alternative, as it specifically attacks the cancer.  With the antibody treatment being relatively new and costly, it requires special approval before it can be given by the NHS, hence a case has to be put together/forward for why the antibody treatment is being requested for the patient in question.

It seems that an antibody treatment is not always appropriate, as it depends on the patient's medical history etc, but the doctors looking after myself felt that it could (combined with a stem cell transplant from a donor) still offer a potential cure for my condition - The doctor that I spoke to was hesitant to put a number on the percentage cure rate, but did make it clear that it's not good, which is presumably partly why this treatment requires special approval, i.e. there is a balance to find between cost and the potential benefit to the patient.

Should an antibody treatment be approved for myself, which the doctor I spoke to seemed to think was more likely than not, then I will need to have six antibody treatments, followed by a PET scan to see whether they're working, and assuming they are a further few antibody treatments (the exact number to be decided on later), before finally having an allogeneic (from a donor) stem cell transplant.  Therefore, given that each antibody treatment is three weeks apart, and that the allogeneic stem cell transplant involves a few weeks stay in hospital, then the total duration for the treatment (even in the optimistic scenario) is over half a year!

The antibody treatment itself is done as an inpatient, even though it doesn't take very long to administer, as there is a possibility of having a reaction to it (with symptoms similar to an infection), so it typically involves a day or two in hospital to ensure there are no adverse effects.  The antibody treatment is just administered intravenously (via IV), and over exactly how long depends on the patient, as it may be slowed down if going too quickly causes a reaction (there are also medications that can be prescribed to help with this too).

So, until I hear whether the antibody treatment is approved, I just need to go for weekly blood tests, and at the same time get the hickman line flushed and its connectors changed.  I'll no doubt be having a bit of a read-up on antibody treatments too, as the hospital will shortly be providing me with some information.

Wednesday 1 August 2012

Treating an infection

About a week after having the second IVE chemotherapy I started to feel a bit ill, but as coincidence would have it I had a hospital appointment for a lung function test that day, so I thought I'd go along to that and whilst I was there mention to a nurse in the haematology clinic that I wasn't feeling so great.  I left home a bit early for the lung function test, as I thought I'd try to see a nurse in the haematology clinic first (just in case they decided it wasn't worth doing the lung function test at that time), but it took a while to get a parking space, so in the end I just went straight to the lung function test.

The lung function test is pretty straight-forward, as you're really just asked to breath in and out of a tube using a mouthpiece (what is essentially a glorified peg is put on your nose too); A computer is connected to the other end of the tube so that it can analyse the air content, flow and volume.  It probably takes around thirty minutes in total, as there are a few different types of breathing tests to be done, and you do most of the tests at least twice to ensure that the results are consistent/representative.  You're guided through each test with instructions like: "breath normally", "take a deep breath and hold it" and "breath out as fast as you can"; The only thing that varies from one test to the next is the sequence of and exact breathing instructions given.  Personally, I find the hardest part of the tests is being asked to breath out every last bit of air from your lungs, as it's not something that we ever really do in real-life; To a lesser extent, holding your breath can be similar.

After the lung function test, I mentioned to a nurse in the haematology clinic that I wasn't feeling so great, so a blood test was arranged and my temperature was taken.  My temperature was above 38°C, so at that point I pretty much knew I'd be admitted for a course of antibiotics.  I did also suspect that I'd need a platelets transfusion, as that morning I'd noticed a small black (ish) spot had appeared on my tongue and I had some bruises from where my weight had been concentrated when sleeping.  Both the need for being admitted and a platelets transfusion were later confirmed by one of the doctors, after receiving the blood test results and a quick chat, followed by an examination of my breathing (after walking for a bit, I found myself a little out-of-breath and with some discomfort/pain just below my right shoulder blade).

After being admitted to the haematology ward:
in order to determine the source and type of infection some more blood samples were taken (one through the hickman line and one through a cannula), I had a chest x-ray (just in case it showed anything), I was started on a course of antibiotics, and I was given a platelets transfusion.  A further platelets transfusion and a couple of red blood cell transfusions were prescribed over the next day or so, due to my platelets still being low, and my hemoglobin level dropping a bit further.  I was also started on a second antibiotic after a couple of days, as the preliminary results for identifying the infection suggested it might be worthwhile, but that antibiotic was stopped a few days later when the exact infection was identified, as that infection is known to respond fine to just the first antibiotic.

After a couple of days or so on the antibiotics I felt fine again really (diarrhea aside), but the full course for the first antibiotic is five to seven days, hence I needed to stay in hospital for a while longer.  I had that antibiotic for seven days in the end, and during that time I also went for another heart scan (the results of which were fine) and a PET scan (the results for which I'm still waiting).  Even after the antibiotics finished, I still had to stay in hospital, as my blood counts hadn't recovered enough for me to go home; They were on their way up, but were taking it steady.  One of the doctors explained that the delay in my blood counts returning to normal is likely just a sign that my bone marrow needs a rest after all of the treatment that I've had, hence my third (and hopefully final) IVE chemotherapy will be delayed until I've had time to recover.

Note: I'm actually in hospital now, which makes it nine days and nights so far, and I'm still waiting to find out when I will be discharged.  As you can probably imagine, hospital is not the most fun place to be, even though I can make use of the gadgets etc in the teenagers and young adults ward, but I did manage to pass a bit of time in the last few days by decorating my room a little with some drawings of a handful of cartoon characters (there are a few whiteboards scattered around for that kind of thing).  There are some pictures below (click on one to view it full size):

Mickey Mouse
Mike (Monsters Inc)

Bugs Bunny
Boo (Monsters Inc)