What is the difference between a mini-allo, auto-allo, and haplo-allo transplant?

What is a mini allo transplant?

With an autologous stem cell transplant, really, there's only one type of chemotherapy that one gets. And that is like what's considered myeloablative or full dose of chemotherapy. So that's really meant to just wipe out everything. And so then you get your stem cells back.

In an allo transplant, you can do the same thing, you can use high doses of chemotherapy. Typically it's eight days of chemotherapy and then you get your stem cells from someone else and then you go on. What has been realized is that, you know, if you're using the immune system right, then sort of what's the point of the chemo? What's the point of using high doses of chemo? Because that's really dangerous for people.

So about 15 years ago, people started doing things called mini transplants or reduced intensity conditioning transplants. So here instead of using full doses of chemotherapy, we use chemotherapy that's a lot milder. And really, the chemotherapy is to suppress the immune system of the patient so that the new immune system and bone marrow can go in. So it's really more like immunoablation, not bone marrow ablation. And so because of that, oftentimes patients' blood counts will not go as low. Sometimes you don't get as many of the side effects of the high dose chemo. A lot of people don't lose their hair. There's not as much nausea and things like that.

So most of the time now when we do an allogeneic transplant, it is done with a reduced intensity condition or mini transplant. The other is that when I started doing transplants, we only had full myeloablative transplants and the upper age limit to get a transplant, allo transplant was something like 55 or 60 because the chemo plus the transplant, getting it from someone else was so dangerous. If you lowered the chemo and make it a mini transplant, you can do this in 75-year-olds, 80-year-olds. And so you can expand the number of patients who get allo transplants dramatically, and especially for diseases like myeloma, where most of the people are elderly. So it allows you to do allo transplants in many, many more people.

In autologous transplant, we use a high dose of chemotherapy to wipe out the person's marrow. Traditional allo transplants where we had a myeloma and a person's bone marrow. We wanted to kill the myeloma and put in a new bone marrow, which then gives them a new immune system. That's one of the goals. So we would take a person to high-dose chemotherapy, again, destroy the person's bone marrow, and instead of giving them their own stem cells, we would give another person stem cells and then give them medications to suppress the immune system so that they don't reject those cells. That was collected traditional myeloablative transplant. And that was a type of transplant for myeloma that was done in the old days. And it had a lot of problems because myeloma patients are generally older, more fragile.

Myeloma affects the body in many other ways compared to certainly other diseases when we do this procedure like leukemia, lymphoma, myeloma is that as anybody with myeloma knows, it affects the bones, it affects the kidneys, it has multiple effects on the body, became very toxic. And the mortality rates of patients who underwent this procedure was so high. In fact, the first clinical trial that compared this mortality versus auto transplant and chemotherapy had to be closed down because of the allo transplant. The traditional allo transplant did not look too toxic. So then we came up with a different way of doing it, called the mini allo transplant, where the actual chemo that we give is very light and in fact so light that sometimes you don't even need to get admitted for this transplant. You do it with daily visits to the hospital and going back to your home every day.

So those transplants we use what we call lymphodepletion or similar to what we do for CAR-T therapy, for example, just all you need is to suppress the immune system just enough so that donor cells are able to be tolerated by the recipient. And those are the many allo transplants that virtually almost all of the transplants that we do for myeloma in the allogeneic setting are mini transplants now.

What is an auto-allo transplant?

So an auto-allo transplant is basically an auto transplant where you get a standard autologous stem cell transplant. And then after that you're going to do a mini or a reduced intensity conditioning allogeneic transplant. So it's an auto transplant followed by mini. And you might say, well, why would you ever do that? Well, an auto transplant is really good at getting rid of myeloma, right? It's just not good at keeping myeloma away.

So what we found in an allo transplantation is, that the less myeloma you have before you have an allo transplant, the better the transplant will work. So one way to do that would be to try to destroy as much myeloma as possible. And one of the best ways to do that is an autologous transplant. So you do that first, you wait about a month and then you do an allogeneic transplant. So it's a combination thing. It's sort of like if you did a full allo transplant, you get high-dose chemo, then the allo transplant, this is like you get full-dose chemo, but then you wait a little while and then you get the transplant. So separating those two out in time, which makes it a whole lot safer than doing high-dose allo in a patient just all in one.

What is a haplo allo transplant?

So haplo transplants depends on the donor. So most allogeneic transplants that are done are using what's called an HLA match sib. So it's matching these two different sets of proteins and you get half of them from your mom and you get half of them from your dad. And so if you have a sibling, one sibling, then the chance is going to be one in four that you guys totally match. Match 100%.

In the case of a haplo transplant, what you can do is you can be half match so you can get one half from your mom or one half from your dad. So in that way, for a sibling, you can have fully match both sets or match one set of match from your mom or one set is match from your dad. So it's actually three out of four now for a sibling. But if you think about it, if I have kids, I'm going to pass on my genetic information to all my kids or my parents are going to pass their information on to me. So my kids are going to be 100% matched, half matched, and my parents are going to be 100% half match.

And so by doing that, it dramatically expands the number of donors you can do. An important thing is that for patients who are older, who get an allo transplant, one of the most important features is what is the age of the donor? You want to use young, fresh, healthy bone marrow. And so if you're 75 and you get a disease and you need a transplant and you're relying on a sibling, that sibling is probably going to be like around 75, which is older. But if you have kids that are in their forties or thirties, that is much younger, so allows us to use younger donors for older individuals and then you get less of what's called graft versus host disease, you probably get more cure rates.

So it's good to use good fresh marrow. You don't want to use older marrow. So doing a haplo transplant dramatically expands what you can do, the number of donors, and it allows you to use younger donors. You could even if you think about it, you could use grandchildren as donors, as donors, you could use cousins as donors. So it really expands the number of people who can get a chance.

It's estimated that with haplo transplantation, it's probably about 95% of people will have a match, whereas with a matched, a regular full allo, not a haplo, it's probably about 40 to 50% of people will have a match. So it really dramatically allows more people to get transplants. Haplo stands for haploid Identical.

And what has happened over time is that in order to do allogeneic transplant, we have to find a suitable donor. So in the case of multiple myeloma the earliest donors were sibling donors who were matched or family donors who were matched immunologically. Later on, unrelated donors were found, and there's been many transplants performed with unrelated donors who are matched to occasionally mismatched.

In certain patients so that the genes. about 25, maybe 3% of patients have a matched sibling donor by going to the unrelated donor by looking for a match. And really donors, we can expand so that somewhere between 50 to 80% of patients may have fully matched unrelated donors. However, there's still a proportion of patients that don't have a suitable donor. And then we need to consider what in the past has been called alternative donors.

One type of alternative donor is haploid identical, which means that a family member who is half matched. So, for example, a sibling who is half matched where they inherited the same set of genes from one parent, but not the other. That would be a haploid identical sibling and then a parent or a child, but also naturally being. haploid identical.

So those haploid identical donors can also be considered as transplant donors. And that's a very exciting thing, is that the results of haploid identical transplant. Have now are now approximately the same as unrelated donor transplant. The other alternative donor would be cord blood transplant, and there's just been very few cord blood transplants performed for most myeloma compared to leukemia, for example.

There's a lot more cord blood transplants for leukemia, a lot more cord blood transplant for pediatric population. But in multiple myeloma, we would consider the next step after matched unrelated donor might be to consider haploid identical transplant.