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How do you balance graft versus host disease and graft versus myeloma effect?

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So with graft versus myeloma, that would be the immune cells

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you get from the donor attacking the myeloma and getting rid of it.

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That's good.

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The other part, though, is that the immune system is smart.

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It can recognize you from me, but it's not smart enough

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to recognize cancer from non-cancer.

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So the immune system, besides recognizing the myeloma,

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might recognize other things in you, other things in your body.

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So if the immune system attacks other organs besides the myeloma,

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you might get sick from that.

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So in the early phases of allo transplant,

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you can get a skin rash, you can get damage to the gastrointestinal

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tract where you get diarrhea, nausea, or you can get damage to the liver.

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So those are really early

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on the three places where you get graft versus host disease.

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Later on, you can get the immune system attacking almost any organ in the body

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That's more remote after the transplant is done.

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But if you get a bad enough immune attack, that itself can kill you.

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Okay. So graft versus host disease is bad.

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Initially, we might see someone get a little bit of 

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graft versus host disease because graft versus host disease can be mild, moderate or severe.

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If you have get a mild form, maybe you get a rash

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and it might go away by itself.

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And a lot of times we consider that a good thing because it tells us

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that the immune system of the donor is now recognizing something as being foreign.

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So we want that to happen.

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If you have an immune system going in, you want it to recognize the myeloma,

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You don't want to recognize the other parts of you,

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how do you separate that out?

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Can you separate it out?

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So people have tried to do this.

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This is the holy grail of allogeneic bone marrow transplantation.

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How do you kill the cancer but not kill the person?

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Right.

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So the long and short of it is is I don't think it can be done.

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I don't think you can do it.

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So part of it is to try to separate them out in time.

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So maybe what you do is you put the immune system in

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and you dampen it in the beginning to try to prevent graft versus host disease.

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And, it may or may not have activity against the cancer.

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Later on, as you move down and you've established

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the immune system's gotten sort of used to things, right.

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So it's not going to be so reactive.

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So you don't have as higher risk of getting graft services,

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then maybe you come in with something

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that will stimulate activity against the myeloma cells.

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So maybe what you should do is you should separate them out in time

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instead of just dumping them in and just letting

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whatever it wants to do to happen. Right.

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Try to sort of coordinate it.

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So a lot of the research now that's going on  in allogeneic bone marrow transplantation is

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to control GvHD in the beginning

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and then give people things afterwards

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to try and

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stimulate an immune response against the tumor.

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So that I think is going to be the way to go.

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Like one extreme version of that might be

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you do an allogenetic transplant and then six months later

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you harvest the immune cells, which are going to be from the donor.

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You make those into CAR-T cells and you put them back into a person.

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But so you boost that immunity through CAR-T cell therapy.

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So that is complex and probably expensive

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and perhaps more dangerous, but that may be a way of really making

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allogeneic transplantation work well, because the one benefit you get

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is that you get a healthy person's immune system, right?

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And that may be really good for CAR-T cells.

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And so that's like a real extreme version of like doing something

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after the transplant, you know, after you've gotten over the hump

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of maybe getting a risk of graft versus host disease.