Friday, 15 November 2013


We’ve been dancing with Mr Brownstone. He’s been knocking. He won’t leave me alone. I used to do a little but a little wouldn't do it so the little got more and more
Mr Brownstone – Guns 'n Roses

Find myself discussing the area under a curve today. Gets me thinking about my sixth form maths lessons, and "crapulous" as we used to call calculus. We were so very droll. We had mutated song lyrics for all our teachers. For Mr Brown, who look applied maths, it went "We've been working with Mr Brown / He's been teaching but we don't understand / I used to do a little but a little wouldn't do it, so now I don't do any at all" and so on. Ha ha.
Gyles informed me, with some conviction, the other day, that all maths is easy. I explained that the wonder of maths is that it just goes on and on, so no matter how good at it you are, there comes a point where you have no idea what they're talking about, any more. Which is a bit like myeloma

"You have interesting cytogenetics", says today's consultant.
Interesting, in this context, means complicated and unusual. It is not a compliment. Myeloma cells have damaged DNA (otherwise they wouldn't be cancerous), but not everyone has the same mutations. To add to the confusion, there are increasingly sensitive tests, and more sensitive tests will show more things up (because myeloma cells are actually not all clones, but are colonies with different mutations, and they continue to mutate, for the worse, as the disease progresses). Something which is significant when found using an insensitive test may be less significant when only found using a more sensitive one. Testing capabilities have come on so fast that these tests produce more data than anyone can interpret, but there are a number of regularly found mutations, and for a few there's evidence to show they are associated with poorer outcomes. Of all the common mutations, two are particularly seen as risk factors: "t(4:14)" – where bits of chromosomes 4 and 14 have swapped, and "del(17)p" where part of chromosome 17 is missing. I have del(17)p meaning (as my test results bluntly put it) that my myeloma is:
"high risk, associated with shorter OS". Where OS means overall survival.
I did know this already, but today is the first time I really discuss it with a doc.

On the other hand, we look at my beta-2-microglobulin levels today. I've read other people's discussions of these before, but never known the significance. ß2-M, I learn, is involved in protein turnover. More of it indicates more protein activity, i.e. more myeloma. Mine, at diagnosis, was 2.6mg/l. That's not normal (which is <2), but it is nowhere near the thresholds for the International Staging System of myeloma. So I am "stage 1" on this measure, with a median OS of 62 months (vs just 29 months if I was "stage 3").

So we don't really know what kind of beast my myeloma is – aggressive or indolent.

We go on to discuss my remission. He measures my light chains vs pre-SCT, rather than pre-chemo and so assesses I've had only 90% reduction, which he calls "very good partial response", which is not "very good" at all, when I've been considering mine a "complete remission". But it does depend on where you measure against – the last time I had this discussion we measured vs my levels at diagnosis, which represents a much bigger fall. It occurs to me that, given myeloma's continual progression - meaning it may secrete less over time; and the amount of treatment - meaning there's no longer a meaningful baseline; that we can never really know what we're measuring against, any more. So all the percentages are unhinged. The other test of my myeloma activity – from the bone marrow biopsy – is clear "morphological remission".

So we don't really know what my myeloma is doing, right now. Except I don't seem to be suffering, and nothing seems to be changing.

Finally, we discuss treatments. He's involved in a clinical trial about "mini-allo" transplants. I ask about the difference between that and a "full-allo". Basically, it comes down to how you think transplants work, and why donor (allogeneic) ones might be curative when "auto" ones are not. If you think, as some do, that the aim of an allograft is to destroy all the myeloma in the body, and then put in "clean" stem cells, then it is important to really blitz what's there – we're talking chemical warfare (high dose melphalan) and nuclear warfare (total body radiation).

But if you think that these treatments rarely eliminate myeloma completely; that the problem isn't that one's own stems cells are contaminated with myeloma; and that the benefit of a donor is that the "graft vs myeloma" effect may be what cures, then it's less important to be so aggressive. There seems to be evidence emerging that a mini-allo can be as effective as a full one, provided that consolidation treatment is taken in the months while the immune system is suppressed, to keep the myeloma down until the graft takes hold. (That means having the transplant and then some chemo – probably bortezomib or lenalidomide – in the months immediately after, but let's not dwell on the practical implications of that.) The long and short is he reckons this can deliver similar long term outcomes, at lower risk. (Lower, not low.)

At this point all I can observe is that we've clearly articulated that we don't know how stem cell transplants work. Not bad for a course of treatment every bit as traumatic as an organ transplant or an amputation. We don't really know how bortezomib or lenalidomide work either, come to that.

What a holy trinity! We don't know what my myeloma is, we don't know what it's doing, and we don't know how the treatments work.

Yet that is the basis from which we must make treatment decisions (which brings us back to the area under the curve). But I think that must be the subject for another post, once my head has stopped swelling.

As light relief, let me tell you about Laplace transforms, and Green's functions...
A Laplace transform is a linear operator that transforms a function f(t) to a function F(s) with complex argument s, given by this integral:
By contrast, a Green's function, G(x,s), of a linear differential operator L(x) acting on distributions over a subset of the Euclidean space Rn, at a point s, is any solution of the Dirac delta function:
Taken together, they represent the point at which university maths got too hard to me. I have absolutely no idea what either of them means. You may feel much the same, after reading all this.

I get up around seven; get out of bed around nine. I don’t worry about nothing, because worry’s a waste of my time
Mr Brownstone – Guns 'n Roses


Unknown said...

Jesus Alex. When will this bastard disease leave you alone long enough to give you a bit of peace of mind? Thank goodness you ‘don't seem to be suffering, and nothing seems to be changing.’ May that continue for a long time to come. I love you. xx

Anonymous said...

Hi Alex, I happened upon your blog in the Myeloma Beacon's blog aggregator. I am impressed with your posts and our paths are very parallel except I have ten years on you! I was offered a slot in a carfilzomib clinical trial at the NIH near Washington, DC last year. I was one of the first newly diagnosed patients to receive it.....guinea pig....and I luckily had a great response. I go back Monday for a PET CT and bone marrow biopsy ( my fifth in 18 months) per protocol. Happy times! I wish you all the best and hope you have permanent remission. Regards, Terry from New Jersey

Anonymous said...

Hi Alex,
You've perfectly summarized what myeloma is. "We don't know". At the end of 6 cycles of induction chemo, I got two new bumps on my skull. Neither my regular oncologist, nor my myeloma specialist could explain why my blood numbers could look so good but I could be developing bumps on my skull like I had right before my diagnosis. Thankfully, they went away with my auto stem cell transplant. I'm now at day 40 post transplant and doing quite well. My doctor suggested I think about an allo for the future. This is more than I can process emotionally right now. Your explanation of the difference between a mini and a regular allo is the first time I've ever heard it put in those terms. Thank you for helping me learn something and for being such a clear and rational voice in the midst of the chaos of myeloma. When I read your blog it helps me to feel not so alone. I am also high risk but stage 2. Please continue to post your thoughts. I wish you all the best.

Alex Bicknell said...

Mr Brownstone, he won't leave me alone...

Alex Bicknell said...

The doc was discussing carfilzomib with me too. I'm happy to have only used relatively "conventional" weapons in the fight so far, and also happy to know more and better are available. We talked about vaccines too. Lots to be hopeful for. I hope your BoMB isn't too painful today, and your scans are clear.

Alex Bicknell said...

I wan't expecting that conversation on Friday - just went in to learn my light chain numbers. I'm not sure whether I know how to emotionally process it all either - I think part of my emotional systems has shut down, to be honest, as a coping mechanism.

I think mini-allos may be the way forward, along with vaccines. That may be the function cure we're waiting for. So we might have to get our heads (and our bodies) round it in time.

Strength to you as you recover from the SCT. Better days are coming.