“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