What’s in a number?

I mentioned before that there’s a particular number which needs to hit 100 before I’d be eligible to enter a clinical trial that I may or may not like to enter. I had the blood test last Thursday, and it takes around a` week to get the result, so I’ll hear sometime in the next three days. I could have waited until after I actually knew the result to tell you that, but I decided you blog-readers might all like to share in the agony suspense of waiting. Suspense is an excellent literary device. We’ve just read ‘Rebecca’ in book group and I was surprised to find that almost every chapter ends with a massive cliff-hanger. If I write lots of blog posts with cliff-hangers my ‘hits’ will go through the roof…

So, what’s this magic number all about? It’s my light chains. Or more precisely, my kappa free light chains from my serum free light chain assay. Chances are you’ve no idea what I’m talking about. It sounds like something from Star Wars. I could go into a more biological explanation with pretty pictures (as myeloma blogger extraordinaire Wendy has pointed out, they’re actually quite pretty!) and might do that another time. For now, here is a more potted idiot’s English Literature student’s guide to the cell biology of myeloma.

Plasma cells are a type of white blood cell. They are like little factories which pump out antibodies (immunoglobulins) which are part of your immune system and come in all sorts of bespoke varieties to target whatever variety of nasty thing needs attacking. These antibodies team up with all sorts of other awesome parts of your immune system like T-cells and Natural Killer cells (yes, you really have those inside of you – who knew?) My level of knowledge goes all hazy at this point but if you look it up on youtube there are little films explaining it all with someone drawing pictures the whole time to help. It’s cool.

Duff myeloma plasma cells pump out duff antibodies, which rather than being all bespoke and individual and cool are all uniformly duff. Antibodies are protein molecules, so these are known variously as ‘paraproteins’ (fake proteins) or ‘monoclonal proteins’ (uniformly duff proteins). For around about 70% of myeloma patients (ish – I haven’t checked that) these will be measurable in a simple blood test. So these myeloma patients watch their numbers go up and down as a cancer marker: they might be as high as 60 on diagnosis, and then down to say 2 or 1 or (hurrah) 0 after treatment. A normal person would have zero. Brits call them paraprotein or just write PP, whereas, Americans take the M for monoclonal and call it their M-spike, which makes me laugh (Yo dude, what’s your M-SPIKE?) I think that’s because when the lab people do the fancy test on the blood with electromagnetism or black magic or whatever they do, rather than a nice evenly spread range of different types of antibodies they find a whole bunch of duff ones of a particular type, hence you get a big ‘spike’ on the graph of results.

What about the light chains? Well, this is for about 20% of myeloma patients (me included) whose myeloma is so pathetic it doesn’t even pump out full duff molecules just bits of duff molecule. A normal antibody is y-shaped, consisting of two heavy chains and two light chains (this would be the pretty picture). Picture someone doing the Y in the YMCA dance with bat wings, the light chains would kind of be the bat wings. So, my cancer marker in my blood or urine is light chains.  These are measurable in a fancier blood test, the serum free light chain assay (SFLC). Everyone, for some inexplicable reason, has some spare light chains kicking around their blood, but crucially they’d be in a certain normal range. There are two types (kappa and lambda) and they should be in a certain normal ratio. Kappa is something like 8-19 as normal range, I can’t remember exactly the lower bound. For me, the one that starts to go mental is the kappa light chains: so if my kappa and lambda were both high that might be OK, but in my blood tests my kappa is rising out of range and the lambda isn’t, so the ratio is all out of whack. My kappa hit 26 in September, and then 59 and 76 in January at two different labs which apparently tend to have a slight discrepancy. This is the test where it’d need to be 100 to be on the trial, so it feels quite hard to predict: it could easily just be something like 85.

You can’t necessarily compare numbers across patients. Some people might have a lot of diseased plasma cells in their bone marrow and quite low numbers, or vice versa. The way I think of it is smoke and fire: the paraproteins or light chains are the smoke signals that are easy to track from frequent blood and urine tests. But the bit that really matters is the fire in your bone marrow: it’s just intrusive and painful to do a biopsy to get a good look at that, so you only do it every now and then at key moments. Some people have very smoky fires, some people less so (‘low secretors’). Some poor people have smoke which makes no fire (‘non-secretors’) so it’s very hard to track what’s going on. For a clinical trial to know how well the treatment is working, you need some kind of measurable disease so they can watch it going down – so you can’t enter a trial if you’re a non-secretor.

100 is actually a pretty low bar. Quite soon after I was diagnosed, in June 2012 mine were 1270. But some people’s get up to levels of several thousand without any bone damage or other symptoms, whereas I had a lot. My leg, for example looked like this:


You can clearly see where the bone has been ‘eaten away’. Apparently (thanks to Alex the great myeloma blogger for this fun fact) you need at least 30% bone loss for it to show up at all on an x-ray, unlike more sensitive tests such as an MRI, so that big black hole is pretty scary. Essentially, that is because all the dodgy myeloma cells were multiplying and multiplying and filling up all the space in the bone marrow, and intefering with the normal processes whereby bone constantly builds and destroys itself, leaving just destruction. Lots of my bones had holes in, but this was the most obvious and most serious hole as it left my left thigh bone very close to fracturing. I was hypercalcaemic (high calcium in my blood) because the broken down bone was in my bloodstream – which led to constant puking of green bile. I was anaemic due to lack of space for red blood cells. My kidneys were beginning to fail due in part to all the excess light chains blocking them up.

You can also therefore see the reason why I wouldn’t want my myeloma to get too active again before starting treatment: I’m prone to quite a lot of damage at relatively low numbers. It’s important not to get much new bone damage as it’s hard to undo once done, and it hurts. I already had some new spots appearing on x-rays in December. A classic myeloma sign is what is known as ‘pepper-pot’ lesions on your skull, lots of little holes. I had some signs of activity there. I’ve had all sorts of ambitions and fantasies about what I’d be in life, but being a human condiment dispenser is definitely not on the list.

I don’t want to terrify you all, however, much as I’d like to thrill you with a little sense of danger for the suspense to keep you hooked on reading my blog. My full blood counts are all still normal (i.e. I’m not anaemic or anything else, kidney and liver function etc all fine). I felt a lot more pain in my leg last time than any pains I currently have. If I weren’t so closely monitored, I might not even realise what was going on. I know other patients whose numbers have reached higher (including the actual ‘fire’ numbers of bone marrow biopsy etc) before starting treatment at their first relapse.

If my SFLC count isn’t yet 100, I’ve got all my paperwork set up to start treatment at my current hospital, so I do have that option (and sod the trial). Each option is good: it’s six of one, half a dozen of the other in terms of pros and cons, so I may well just let the numbers decide. I will also do a urine test as it’s also possible to enter the trial that way, and it’s possible my numbers might be higher there than in my blood – so that’d be sort of like buying a second lottery ticket, if I can be bothered to wait a bit longer for results from that.

Tune in for the next exciting instalment, which I guess may well be sometime at the weekend! I will also reward you all with the ‘after’ x-ray pictures of my leg, having shown you here the ‘before’ one. There will be titanium! (gasp!) There will be screws (oooh!) There will be a 48cm nail (aah!)

Yours, suspended, the second Mrs De Winter

The first and only Helga the Great