'Living drug' offers hope to terminal blood cancer patients
bbc.co.uk
bbc.co.uk
Having seen both ALL and AML patients relapsing through CAR-T, I don’t think people appreciate either the systemic load or the possibility of treatment failure that exists in real patient populations. Neither was elderly; 26yo female ALL and 5yo female AML. Both dead, both crushing disappointments after the initial excitement.
(For CAR-T therapy, the common remark is “you know it’s working when the patient goes to the ICU” from tumor lysis; but in both cases the patient’s disease outran their engineered T cells)
Re: BiTEs, it's not clear they'll produce durable cures like CAR does. They're just antibodies, and will eventually be cleared. With CAR, if you can get a response, you can generate memory T-cells and control any relapse far down the road.
I was very curious to read that it had such severe side-effects, especially the neurotoxicity. Why such a severe reaction? Does the neurotoxicity have developmental impacts for children that receive immunotherapy?
MLL rearrangements in young children have a particularly vile habit of swapping cell surface markers wholesale. They’re almost certainly more potent when they transform fetal liver progenitors, which seem to retain maximum plasticity. AA died prior to the introduction of second and third generation CAR-T, but stan riddell was part of her attending team, so I have to assume all the stops were pulled out.
MG was different, 26yo Philadelphia-like ALL with 300k WBC refractory to everything. She should have been on ruxolitinib then transplanted. Her disease simply outran her T cells’ ability to divide. It was unreal. And she was a single mom.
I will never forget either case. Even as just an “attached” fellow, it’s hard to watch. More so (for me at least) than older patients where you can reasonably guess what’s coming next. It just feels so unjust.
Anyways. Let’s hope I’m wrong and 2nd/3rd gen auto and allow CAR-T can put these kinds of cases into durable remission for the rest of their, hopefully long and healthy, lives. Because right now, nothing does.
Why is that not also true in chemo patients?
A lot of chemos are some type of poison, only slightly worse for the tumor than it is for the rest of your body. It doesn't die fast enough (and if it did, you'd be killing the rest of you too). Think months / years with chemo vs. weeks with CAR-T.
I know a child with leukemia who recently started chemo. They had him on sodium bicarbonate and other medication to reduce the acidity of his urine (to compensate for the increased amount of uric acid). However, they only had him on it for the first few days of chemo. My understanding was that the bulk of the chemolysis occured in that period (though I could be mistaken).
Chemo kills everything in your body, just the cancer a little bit more. You do the chemo, wait a few weeks, then do chemo again, wait a few weeks, maybe get a scan, do chemo again, wait a few weeks, ..., maybe in 6 months if your treatments are going well you keep going, maybe they switch you to something else, maybe this round is done and you take a break for a while. You wait because if you don't, the poison kills all of you, not just the cancer.
https://www.youtube.com/watch?v=FlK-PeCfezM
The CAR-T segment starts at 27:30.
We also distinguish "live vaccine" from "inactivated" or "killed" vaccines, for example OPV the cheapest way to prevent polio is a live vaccine, it's a version of the Polio virus that has adapted to a slow life in a cold medium, and then you eat it (literally, it was traditionally given by adding one drop to a sugar cube, the patient eats the sugar cube, delicious) and your gut goes "What? This is alien - kill it" and you become immune to Polio before it spins back up and causes any harm.
Live vaccines are dangerous (which is why we don't use OPV in countries with no polio and plenty of money, even though it is more effective than any alternative) and no doubt this drug is also dangerous, but hey, it's for people with a terminal disease so what's the worst that could happen?
Why do you need to send your blood to an “inferior” healthcare system?
I.e. zombies are magical creatures, even less plausible than godzilla.
I also curmudgeonly think that Game of Thrones lost its appeal when it stopped being about political intrigue and became yet another silly magical zombie movie.
If it weren't for the zombies, the political story would just be about people fighting each other for advantage. The zombies add a tension between that and a common cause, since the threat faces them all; much like the world we live in today.
Even Lord of the Rings just had to bring in a zombie army at the end, but fortunately didn't spend much screen time on it.
The only one I like was the Jason and the Argonauts one where the hero fights a group of skeletons. The herky-jerky Harry Harrison animation is a pleasure to watch. And it was original.
(As for GoT, how many movies have had dragons?)
So the very first scene of both the books and tv show?
Now I'm even more worried! How can the do that?
The dullards who fight them never think of putting them in a hamster wheel and generating perpetual electric power.
Besides, the zombie armies never seem to have any logistics to keep them supplied with brains, or any support logistics at all. There's a reason why predators never evolved armies.
(Ok, army ants are predators. But they evolved logistics!)