What is an allo transplant?

What is an allogeneic(allo) transplant?

There are really you can break down transplants into two different types. So there are the ones that most patients undergo with myeloma, which is an autologous stem cell transplant. There you are taking the stem cells out of you, giving the patient a lot of chemotherapy and then giving the stem cells back. So really the stem cells there are the antidote for the chemotherapy, because if we just gave the high dose chemotherapy, you'd have no blood production for months. If we give you stem cells back right after the chemotherapy, then your blood cell formation will come back in a matter of weeks. So it's really the antidote. It doesn't fight the cancer, it's just merely an antidote for the chemotherapy. And so the chemotherapy support that fights the cancer, the other type of transplant is an allogeneic transplant where you don't get stem cells from yourself. You you get that from someone else. So it could be a sibling, it could be, you know, another relative, it could be an unrelated person that you find through one of these bone marrow drives. It could be from cord blood. And so but it's just from a different person. So allogeneic is different from autologous just because it's primarily from a different person.

So if chemotherapy in an autologous transplant is a part that fights the cancer, what happens in an allo transplant. In an allo transplant, we give chemotherapy just like we do in an auto transplant. We may give lesser doses of chemotherapy, actually, but then we give the stem cells right after that. So when we do that with an allo transplant, one benefit is, is that there's no myeloma in the bone marrow because we're getting it from a healthy person. Right? So that was originally the thought of using it from someone else. But the major part of it that you get is you get someone else's immune system right? So the immune system can kill cells, but it does it in a different way than chemotherapy. So if I had someone, I gave them chemotherapy. Chemotherapy didn't work at all. So I would say, look, they have chemo resistant disease. I could give them immune cells and those immune cells could kill the tumor because immune it the way cells kill with immunity is totally different than the way they kill from chemotherapy. Almost all chemotherapy kind of works the same way, but immune cells are different.

So in an allo transplant, when you get immunity from the donor, it is really like you're getting the immune system from that person. So the immune system from the person comes into you and that immune system says, oh my god, all of this stuff is foreign to me. It's not me. So hopefully one of the things that it recognizes as being foreign is your myeloma. So if you can recognize it as being myeloma, even if that myeloma can't completely go away with chemotherapy, an autologous transplant where it's mephalan maybe in an al transplant where the immune system is at play, that is supposed to be the cancer fighting part. It's the immune system. It's not the chemotherapy. So that is the major difference in those two approaches. Right?

So a transplant is a different kind of transplant where you actually transplant a person's bone marrow and substitute their bone marrow with another healthy person's bone marrow. So when you have multiple myeloma, the concept is that myeloma is an immune tumor and it's also an immune sensitive tumor in that for a person to get myeloma, at some point, the person's immune system fails to take out the few myeloma cells they have. So literally all of us are having cancer producing mutations all the time, and majority of those mutations are getting eliminated by our immune system successfully.

In the allogeneic transplant setting, we actually do chemotherapy not just to destroy the myeloma. We also use that chemotherapy to put in a new immune system or a new bone marrow from another person, which then confers a new immune system upon the recipient. And that new immune system can take care of the myeloma by mounting an immune attack.

The good effect is that in there are people who have received allogeneic transplant 20 or 25 years ago and have never relapsed, essentially been cured. But also the bad thing is that we cannot predict who needs it. In actual practice, only one or 2% of patients who get myeloma eventually end up doing an allogeneic transplant. And the people who select for that procedure are people who are exceptionally high risk. So people who have plasma cell leukemia, cell leukemia, for example, we have multiple high risk mutations. People are very young and have multiple high risk mutations. People who for whom chemotherapy does not work at all. So are chemotherapy refractory patients and in some cases, people who have failed all the lines of treatment but are still robust enough to undergo this transplant.

The major problem with this transplant is that it does have a side effect known as graft versus host disease, which is an immune attack mounted by the donor cells on the patient's body. So this side effect is kind of a mix of double edged sword in that a little bit of graft versus host disease correlates with an immune effect against the myeloma, too. But too much graft versus host disease is sometimes fatal and sometimes a horrible nuisance on the patient's life for many, many, many years. So it is a you know, I would say a procedure that should be used only very selectively and sparingly. And it does have the potential to transform high risk myeloma into a more manageable disease. And in some cases, that's the only thing that's left for a patient to do because nothing else is working. And that's kind of setting in which we use it now.

However, this has led to a whole host of other things that have come on. Just the successes that we have with that transplant have shown to the myeloma doctors that the immune system is effective at kicking out myeloma, at least in a subset of patients. That has led to a whole host of studies where we try to use cells which are powerful immune cells, the T-cells, and convert them into more important cells that can kick out myeloma. And so the CAR-T of the whole CAR-T revolution is spurred on by the view that T-cells can eliminate disease. Same thing with T-cell receptor modified cells, same thing with sometimes vaccines. All of them derive that principle of immune elimination of myeloma to achieve a cure.