LSU Health Pediatric Hematologist/Oncologist at Children’s Hospital, Zach LeBlanc, MD talks about a bone marrow transplant to save a baby from a rare disease.
Interview conducted by Ivanhoe Broadcast News in 2023.
When did you first meet Miller? Did he have pneumonia when you first met him?
LeBlanc: The bone marrow transplant team has a good relationship with the immunology team. They were following Miller and had reason to believe that he had something different than what he ended up having, but that would still be treated with transplant. They wanted me to meet him at that time. He was in the ICU sick with pneumonia like you mentioned that’s right.
He was diagnosed with a real genetic disorder. Can you tell me a little bit about that?
LeBlanc: I think globally, the best way to understand it is it’s a form of SCID. That stands for severe combined immunodeficiency. Our body’s immune systems are very much regulated based on the types of cells that are there. For Miller, he has a specific genetic defect that doesn’t allow his T cells to function appropriately. There are a lot of different mutations that can lead to the same phenotype or how patients present with severe infections or not gaining weight or having lots of diarrheas, in the first year of life is just actually really rare. But the treatment for all those things is the same, which is to give them, somebody else’s functioning immune system.
Before we get to the given in the transplant, tell me what’s the danger of this for Miller? Could this be threatening for him, and does he have an immune system?
LeBlanc: Before the transplant, his immune system was incapable of responding to even the most benign of infections. He ended up having a very severe infection but viruses like flu or RSV are life threatening to patients with SCID.
Did he get COVID?
LeBlanc: He did get COVID. For other patients with SCID, sometimes get what we would call atypical infections or infections that people with normal immune systems don’t get because their immune systems are able to clear it so quickly. For him, that’s what he ended up having. Not only was it an atypical infection, but he got very sick from it. It wasn’t until he got the appropriate antibiotics that he was able to get better.
Is the only treatment for this now is a transplant?
LeBlanc: The only curative treatment for it is a correct transplant.
How did that work? Does it put him more at risk because he was so little or not?
LeBlanc: Here at Children’s, the transplant team, we treated a lot of different ages from little bitty babies up until their early ’20s. We’re especially trained to transplant young children like that for a variety of different conditions whether it’s cancers like leukemia or neuroblastoma or things like this, which would be SCID. For patients normally or usually, I guess with patients with not-so-rare forms of skid, patients are identified on newborn screen, like when they’re very young in the first or second week of life and referred to our team before they even were to get an infection like from what Miller had. His version of skid was different and unique, the newborn screen was normal. That’s why his diagnosis was delayed. But once we had the diagnosis, then it was two strategies. One was to control the infections. Patients do a lot worse through transplants if they have active infections. Second was to find a donor for him, work up that donor, make sure that donor was a good donor for him, and get him admitted for transplant.
Was it a family member or a stranger, his donor, do you know?
LeBlanc: He had an unrelated donor; he doesn’t have any siblings. Your fully matched sibling is your best possible donor, that wasn’t an option for Miller. We went to the NMDP and found an unrelated donor that matched him well. We’re lucky enough to have that donor agree and get them worked up quickly. I would say on average for unrelated donors takes at least six weeks, that would probably be the fastest that it ever happens. Sometimes it takes us more than three or four months to get a donor identified and ready to donate.
To get bone marrow, how do you take that?
LeBlanc: There’s two ways that donors give stem cells. One is with a marrow collection, so that’s with the bone marrow harvest. The bone marrow is the squishy stuff in the middle of your bones. It’s taken out with sequential bone marrow aspirates at a NMDP approved donor center.
Just basically with a needle?
LeBlanc: Yes, a needle into the back of their hip. The other way if somebody does not want to do bone marrow harvest because that would be the especially in pediatrics, that’s the preferred stem cell source, would be what’s called a peripheral blood stem cell collection. That’s not dissimilar than dialysis, if you think about it. To donate PBSC’s, you get your body gets stimulated to make a very high amount of white blood cells. Then after five days of that, you go to a Phoresis Center. You’re connected to a machine that collects the stem cells from you, and then the bone marrow product and the PBSC product are handled very similar after that.
How are they giving them to Miller?
LeBlanc: It’s very similar to a blood transfusion. We have a lot of patients that think that’s like we’re like doing surgery, like we’re cutting bones open and like putting cells in no, we don’t do any of that. It’s very similar to a blood transfusion. It comes in a bag that the lab here processes once it’s received from the donor center. We infuse it, usually the same day. If it requires a lot of extra processing for various reasons, it may be the following day.
How long does it take until you know if it’s worked?
LeBlanc: One of the things that must happen, and I think the garden analogy is really helpful here. Right now, everybody’s bone marrow works well. It makes normal blood cells. For Miller, he had a very specific defect in his T cells, but the other blood cells in his body, his red blood cells, and other types of white blood cells, were very normal. His blood counts were normal. He needed to receive chemotherapy prior to, so that all of those other cells could be killed, and the garden could be “Emptied” so that there was room for the new stem cells to come and grow. The first thing that must happen after these cells are infused, is we need to see evidence that their blood counts are normalized again, because not unsimilar to when we give patients chemotherapy, your blood counts go down. That’s one of the side effects of chemotherapy. For at least this period. For all patients that receive transplant chemotherapy, their counts are zero. The first marker of success, or that we know that it’s working, is when we see their blood counts normalize. That is a sign that the cells are there and that the transplant is working so far, but there are a lot of different reasons that we transplant patients. For instance, if we transplant somebody with leukemia, the goal is very different than if we transplant somebody like Miller who has SCID. For leukemia what we’re trying to do is make sure that the leukemia doesn’t come back. They get bone marrow testing to make sure that it’s not there. Oftentimes within 30 or 60 days, we know that the leukemia is gone. For this type of problem that Miller had for patients with SCID, what we’re looking for is evidence that this immune system has grown and matured and is now able to operate like a normal immune system. There are several tests that we do. It takes about 6-9 months after transplant before you know that somebody with these problems is “Cured” or that it’s a success. The final test or the thing that always, orients the families, is good evidence that your immune system is working if it responds appropriately to vaccinations. There are a lot of different steps for your body to see a new vaccine, to form antibodies to that vaccine. Then for those antibodies to persist for a while, and once they’re ready based on different laboratory numbers, we will give them the same vaccines that two-month-olds get. Then once they’re complete with the series, about a month or two later, we’ll check the levels of antibodies to those specific vaccines in their blood. That is the moment where they’re again cured and then it’s a success. I guess there are things along the way that are like markers that it’s working. The ultimate cure is when they form their antibodies. Their own immune system can respond to vaccinations.
Now, Miller didn’t get to do that to me if it’s the first one.
LeBlanc: COVID has been hard. I remember when the pandemic was first beginning, we had several patients who had very similar presentations and difficulty with having that first time that blood counts normalized after they got COVID-19 when it all happened around the time that the infusion was happening that he developed COVID. We don’t know if it was like the actual viral infection, like the actual COVID-19 infection, or excuse me- the Rendisivia, the antiviral that we used to treat COVID-19 that caused his stem cells not to work the first time. We in that situation usually give them at least about a month or so before we like, we need more cells. The donor was quick to respond the second time and gave us more stem cells. We had a couple of different bone marrow tests that we did on Miller that showed that he didn’t have any evidence of donor engraftment. He responded really well to the second infusion of stem cells and has had great counts ever since.
How long ago was this?
LeBlanc: He’s about six months out from the second one in it. The second one was about six weeks or so after the first one.
Is this a cure for him?
LeBlanc: We haven’t gotten there yet. He’s not quite off. I think a lot of people are familiar with solid organ transplants because there are a lot more people in the world who get solid organ transplants. If you are a person that gets a heart from somebody or a kidney from somebody, those patients are on what’s called lifelong imino suppression. That’s to make sure that they don’t reject that organ. For bone marrow transplants, it’s different. They’re only on immunosuppression or different medicines that protect the new immune system as it’s growing and getting used to the new body for about six months or so. He’s not quite there yet, he’s not off his immunosuppressants. Once he is, and we wait a few months, and we will be able to start the vaccine series again and then see if his new immune system is going to function. There’s no evidence right now that would suggest to me that it’s not going to happen. We just have to wait, if you go back to the garden analogy, we just have to wait for everything to mature and grow to normal levels.
What happens if it doesn’t take? Will you need another step, a cell transplant? What?
LeBlanc: It’s certainly possible, although the rates of that are low, especially with how good his counts have been. We can also, this may be like a blessing in disguise if you want to think about it that way. When he got the second transplant, his bone marrow was essentially empty. There weren’t any more of his stem cells left over either. He has remained 100% donor in all the testing that we’ve done since that time, some patients are similar to him but do have lower levels of what’s called donors or the percent of the donor cells in their blood. But he so far has been at 100%, so while I never say never, I would say his risk of that’s low.
He can go on even though he’s had a very rough first year and a half, the rest of his life could be completely normal.
LeBlanc: Absolutely, there are patients that we see in the clinic all the time that are five years out from transplant for this 10 years out from transplant for this. The expectation is that he’ll have a normal life.
Anything I’m missing?
LeBlanc: I always like for people to be aware of the match. I think that’s important. I’m not sure what medium this is going out in. You do not have to have a bone marrow test done. Donating is not like giving a kidney like your bone marrow recovers immediately. The recovery time is significantly less and helps a lot of people. I also always like to make sure that I say that we were very fortunate to find a very good match for Miller. That’s not the case for a lot of the patients that we treat, especially patients that are minorities. If your viewers are minorities, they should go sign up for the donor registry. We need a lot more people of diverse descent in the registry.
END OF INTERVIEW
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