So after the long weekend, on Tuesday, I’ll be re-admitted for another round of consolidation chemotherapy, for probably five or six days. Typically they do two rounds of consolidation and then a transplant, which involves another month in the hospital. They haven’t found a great match, so at the moment it looks like they’ll try a partial match, in which case they won’t do it at Dartmouth Hitchcock in Lebanon, but somewhere in Boston, I guess probably Mass General hospital.
The risks are greater with a partial match, but it’s still successful for some people, and because of the specific cause in my case there is a high likelihood of relapse without a tranpslant, so the potential benefit of a transplant is enormous and symmetrical to the risk of no transplant. I don’t know a whole lot about the transplant process yet, and I may be repeating myself some here, but the basic idea is that my bone marrow has a mutation (inversion on chromosome 3), which caused it to produce white blood cells that didn’t mature. Normally the bone marrow produces white blood cells that mature into different kinds of cells that do different things, in my case the cells aren’t maturing and the young undifferentiated cells began to crowd out the mature white blood cells and the red blood cells that carry oxygen. So we kill off all the immature cells with the chemotherapy and then take someone else’s bone marrow, and ideally, it grows into my bones and produces healthy blood cells.
The search is for Human Leukocite Antigen (HLA) matching, which is the fancy technical term for the proteins on the outside of cells that the immune system uses to identify which cells are part of the body, and which are foreign invaders. The better the match, the less of a likelihood that the donated immune system attacks the rest of my body as foreign, which is known as graft-vs-host disease (GVHD). It’s similar to other organ donation concerns, except normally they’re concerned that the recipient’s immune system will attack the donor organ, in this case the donation is the immune system itself, so the concern is more about it attacking everything else. The other major concern seems to be that the donated immune system takes hold in my bones. Apparently having some symptoms of GVHD is actually reassuring because it indicates that the donated immune system is in fact doing it’s job, and it could even potentially target any remaining blast cells (cancerous immature immune cells).
The difficulty in finding a good match is because they’re hoping to match ten antigens (ideally, based on research about which donations have been most successful), two known as HLA-A, two as -B, two as -C, two as -DRB1, and two as HLA-DQ. The criteria seem to grow more specific as we collect more information about the genome and which transplants are more successful, so I think they used to look for six markers, then eight, now ten. To better understand the odds, I looked up HLA markers on wikipedia, and found there are 2,884 HLA-A alleles, 3,589 HLA-B alleles, and 2,375 HLA-C alleles; there are 1,540 HLA-DRB1 alleles, and theoretically maybe 34,528 possible combinations of HLA-DQ type alleles. (Alleles are variations of a given gene.)
A very simplistic (and inaccurate) estimate of the relevant variability here would be to simply multiply all these numbers together, but in reality not all these combinations are likely to occur, I’m sure there are strong correlations for certain sets of alleles across markers, but it’s still helpful to get an idea of why matching is so difficult. It’s interesting that there is such tremendous genetic variation in this case because our ancestors seem to have gone through some genetic bottlenecks in the past that reduced our variation in a lot of ways. But there seems to be evidence that humans actually seek out genetic variability in mate selection — there is an obvious benefit to increased genetic diversity in offspring, that’s the whole reason sexual reproduction exists, and in retrospect it’s not surprising that that benefit would be compounded for immune systems. In other words, the reason we have such great diversity in our immune systems is probably that we’re actively seeking mates to maximize the diversity — for the last 150,000 years we’ve probably been actively maximizing the diversity of our immune systems. (This was all a digression I inserted after writing the next part, and I only mention that because I don’t feel like editing together something better than the non-sequitar below.)
I’m feeling pretty close to normal, a bit weaker than I used to be, and I still get a little light headed at times, when transitioning from crouched down to standing up, but I’m mostly feeling pretty much like I used to.
I went to a beach in Maine on Thursday with Justine, which was fun. I had weird feelings about being in public, I guess because of how my immune system was still a little weak, which makes me feel a little cautious about being around lots of people. Last night I went to a baseball game and felt a little more comfortable about that problem. It’s weird feeling normal but also knowing that a minor infectious disease could be life-threatening. I also put sunscreen all over the top of my head, which was a new experience for me.
I haven’t really made any progress on zeeify lately, stuck on a bug, but I’m beginning to think I should just not worry about the final quality of the image at the moment and look into making another fun color-driven app. Maybe that should be spectrify. I dunno. But it’s good to be working on something.
That’s all for now!
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