Blood and bone marrow transplant care at Sanford

Podcast: Providing a second chance by using the patient's own stem cells for treatment

Blood and bone marrow transplant care at Sanford

Episode Transcript

Courtney Collen (Host):

Hello, welcome to our medical series Called to Care by Sanford Health. I’m your host, Courtney Collen with Sanford Health News. Called to Care brings forward medical experts who can give fellow clinicians some advice and guidance that they can use in their primary care practice. And information about when it is time to refer patients and families to more specialized care. Joining me for these conversations is Dr. Joseph Segeleon, who is vice president and medical officer for Sanford Children’s Hospital and a leader in pediatric critical care. But he’s here as my co-host, if you will, to help us dive even deeper into a lot of these topics and provide the best insight in care for our patients and communities. Dr. Segeleon, good to have you back here.

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Dr. Joseph Segeleon:

Courtney, it’s wonderful to be here. It’s good to see you again.

Courtney Collen (Host):

In the fall of 2021 at the Sanford Roger Maris Cancer Center in Fargo, a team of specialists completed the first autologous bone marrow transplant where a patient’s own stem cells are collected and stored. It was a major milestone making Sanford Health one step closer to becoming a national destination for cancer treatment. Joining us to tell us more about the bone marrow transplant program is Dr. Seth Maliske. He’s a Sanford physician who specializes in hematology oncology and has unique training in blood and bone marrow transplants. Dr. Maliske, thank you for being here.

Dr. Joseph Segeleon:

Yes. Welcome Dr. Maliske.

Dr. Seth Maliske:

Thank you for having me.

Dr. Joseph Segeleon:

Just as I think about Sanford as a rural health center and the journey that we’re on, you really think about how fortunate we are to have an institution like the Roger Maris Cancer Center. And so I’m excited to learn more about the program that they’re doing in Fargo, as well as the opportunities and the resources that this brings to our patients and our communities and our providers. I think for us to start maybe we should level set with some of the terms that we’ve we use to describe this field. So maybe you could clear, clear up bone marrow transplant versus stem cell transplant, autologous versus allogenic and those type of things.

Dr. Seth Maliske:

Sure. The term bone marrow transplant versus stem cell transplant. They, they get used interchangeably. Really, when we talk about stem cell transplant, we have stem cells throughout our, throughout our body. But with this therapy, it’s specifically stem cells for the bone marrow. We call them hematopoetic stem cells. They’re the stem cells that are at least partially differentiated so that they can evolve into our blood cells. And so it’s not stem cells that help with maybe orthopedic issues or other health endeavors. It’s, they’re strictly stem cells that give rise to our blood cells. And so that’s why you can use them interchangeably. But what we mean are that the stem cells are, are meant to help grow the, the cells that give rise from the bone marrow, the word bone marrow transplant is maybe falling out of favor because most of the time the stem cells are collected off of the blood. And so when you were introducing me, you, we called it blood and bone marrow transplant. So that’s why we use those words is because actually with newer medicines, we can collect the stem cells off of the bloodstream instead of having to access them from the bone marrow environment. As far as the other terms, you mentioned, autologous and allogeneic, those terms define who the donor is. So autologous means you’re your own donor. So it’s a self donor: we’re collecting stem cells from the patient, him or herself prior to giving chemotherapy, whereas allogeneic transplant, we use allo donors, which means it’s somebody else. It’s not the patient stem cells, but a relative or an unrelated person. And those stem cells then are used to treat a cancer as well.

Dr. Joseph Segeleon:

Thank you. That helps clarify those terms, which I think are often confusing. And I suspect since stem cells are obtained peripherally, that is a lot more appealing for donors, such that they do not have to undergo a bone marrow procedure.

Dr. Seth Maliske:

It’s not only appealing. But it also is more effective. We can collect more stem cells from the bloodstream than we can from the bone marrow itself so we can get higher numbers or higher quantities of stem cells, which are beneficial when we use them for transplant.

Dr. Joseph Segeleon:

As we talk about the center up in Fargo, what conditions and what do patients generally have as far as their disease process that you mostly see and that you utilize these procedures for?

Dr. Seth Maliske:

The use of autologous stem cell transplant or autologous bone marrow transplant is commonly used in multiple myeloma. We use it very often in multiple myeloma, either early on in one’s therapy or sometimes we reserve it for later. But it commonly becomes part of the treatment of myeloma patients. Autologous transplant is also used in relapsed lymphoma. So we don’t do it unless the cancer is relapsed, meaning not cured up front. Those lymphomas include B-cell lymphomas as well as T-cell lymphomas. When we talk about allogeneic stem cell transplant, when we have to use a donor, those, those cancers that we use allergenic transplant for include leukemia. So more traditional aggressive leukemias, like acute myeloid leukemia, acute lymphoblastic leukemia. We also treat aplastic anemia as the most common groups of cancers that we treat with allogeneic stem cell transplant.

Dr. Joseph Segeleon:

So if you will for the providers who are listening and to give them a good idea of what their patients will experience, walk us through a typical myeloma patient with a stem cell transplant.

Dr. Seth Maliske:

Myeloma patients are initially treated with multi-drug chemotherapy regimens or anti myeloma therapy regimens. They receive that medicine for approximately three or four months. And then once the cancer is, is debulked more or less, we then can take them to transplant. The transplant process begins by interrupting that therapy so that their bone marrow is healthy enough to collect stem cells. We then mobilize the stem cells from the bone marrow into the blood. And we do that with the assistance of growth factor medicine. It’s a collection of shots that precede the collection by four days. And then the collection is usually a one to three day event where we’re essentially using a dialysis machine. It’s not exactly like a dialysis machine, but the idea’s the same. We basically create a circuit where blood comes out of the patient’s body through the machine.

Dr. Seth Maliske:

The machine is calibrated to collect a layer of the blood where the stem cells sit and then everything else is returned back to the patient through the opposite side of the circuit. And so blood just circulates around this circuit for several hours, probably four to five hours altogether. And then at the end, we’re left with about a pop can full of stem cells. So it’s blood and plasma and stem cells. And then that bag is then sent to our lab where we use special freezing media so that the cells are unharmed as they freeze and then we store them until they’re needed for transplant. We often interrupt the collection or separate the collection of stem cells and the transplant by at least one week. This allows patients to just recover , helps their platelet count recover, helps them feel a little bit better as we then bring them into the hospital for chemotherapy.

Dr. Seth Maliske:

The chemotherapy is given in myeloma, at least, just over one day. In lymphoma, it’s given over six days. And then after the chemotherapy is given, after the chemotherapy is basically metabolized by the body so it can’t harm stem cells anymore, we then give the stem cells back. So that’s usually about 24 to 30 hour break between last dose of chemotherapy and the giving of stem cells. Everything after that’s just a long recovery for patients. So it’s about two weeks in the hospital until those stem cells start to work. The stem cells are just given by gravity through a catheter. So it’s really just like a blood transfusion. Not a whole lot different, any different than the way red cells or platelets are given by transfusion. But then those stem cells go through the bloodstream and are basically recruited back to the bone marrow environment where they engraft and grow and produce normal, healthy cells. And it takes about two weeks for those normal healthy cells to start being made and push back into the bloodstream where the patient’s safe to go home. And then again, they just slowly recover after that. They usually feel a little unwell for about a month. They start to feel more like themselves by the end of the second month. And then really, I feel, I think completely back to normal by the third month.

Dr. Joseph Segeleon:

So since a number of the patients travel to the Roger Maris center for their care, if I heard you correctly, the patient spends two weeks in the hospital, and then is there additional time that they stay within the proximity of Fargo?

Dr. Seth Maliske:

That is correct. Yes. We keep patients in hospital for that two-week period. Once they leave the hospital, once they’re safe to leave, we keep them in Fargo for another seven to 14 days, just to make sure that they don’t have any early setbacks. It’s just a way to, I think, ensure that they’re well cared for through that first month where they’re the most vulnerable.

Dr. Joseph Segeleon:

And I understand a caregiver comes, accompanies the patient then as well. Is that right?

Dr. Seth Maliske:

Yeah. We define a caregiver up front. Kind of the, the person’s yeah, their partner in this endeavor. They, you know, oftentimes it’s a husband or a wife or their spouse. But other times it’s children or a sibling, but that person is with them throughout the whole journey. And they’re a big part of the team.

Dr. Joseph Segeleon:

If I understood correctly, the cell preps are done at Sanford as well?

Dr. Seth Maliske:

So we have our own lab. We have our own machines, so everything is done at Sanford. So when I describe the mobilization and the collection, that’s all done, outpatient, it’s all done here at Sanford. And then the freezing and the thawing of cells are all done here as well.

Dr. Joseph Segeleon:

OK, great. Now, as far as in those two weeks and then as you said, the recovery period, what kind of complications do you look for? And then after discussing what kind of potential complications a patient may have, maybe we could segue into some survival statistics as well.

Dr. Seth Maliske:

So for the autologous stem cell transplant, the toxicity is primarily of chemotherapy. This is what we call ablative chemotherapy. It’s meant to ablate the bone marrow, wipe out the, the bone marrow. So it’s harming what we hope to be all the cancer cells, but will also injure the normal cells of the bone marrow. Therefore patients almost universally need some blood transfusion, whether it’s red cells or platelets. It also renders them very vulnerable to infection. And that’s the main reason they’re in the hospital for that two-week period. They’re at higher risk for infection because of how suppressed their immune system is, but also because the chemotherapy is quite toxic to the GI tract. So everywhere from the mouth to the bottom and the mouth can get sores, or really the bowel wall can kind of have breakdown and that can serve as a portal of infection for bacteria.

And that is why they’re so much more vulnerable than even the average chemotherapy patient. So taken together the bone marrow and the gut being quite affected by the chemotherapy., we watch those two organ systems, the best. Very seldomly do they need like artificial feeding, but we always tell them that their nutrition is gonna be affected because they feel unwell. There are a lot of times lying in bed for not a long time, a few days, but this just makes it so that they’re maybe a little unsteady on their feet before they leave. So we have to make sure they’re eating and drinking, walking strong on their feet before they go. In addition to making sure they’re well protected from infection. That’s the typical story I convey to patients with autologous transplant. Allogeneic transplant creates a whole new realm of risks.

And that’s because when donor cells are used, they’re used to create an anti-cancer effect. We call that graft versus tumor effect. And that’s what we want to see because it’s gonna help treat the cancer. But another part of the person is just the rest of their bodies. So we call that graft versus host disease, and that can affect really any part of the body from head to toe. So skin, bowel, liver, lungs, really anything become affected. And then on top of it to prevent that graft versus host from happening, we have to suppress a person’s immune system, even on top of what it’s already suppressed from the chemo, and that leaves people even more vulnerable to infection. So these competing risks of outcome, beyond cure, include risks of harm from graft versus host, much higher risk of infection, and then there’s other more, I guess, rare side effects that are life-threatening too, but allogeneic stem cell transplant is, is just a whole new, a whole new level of, of care. It really requires a, a huge team to support people through allogenetic stem cell transplant.

Dr. Joseph Segeleon:

And, what about for autologous transplant? What are the survival statistics at this time?

Dr. Seth Maliske:

As far as treatment related harm? And when I describe that to patients, I, what I mean by that is what are the chances me performing transplant actually shortens your life, not necessarily the cancer shortening one’s life. So that’s treatment related harm or treatment related mortality. With autologous transplant, that’s probably 1%. Maybe one in a hundred people may have a really bad infection or a bad bleeding episode or another event at the time of their transplant caused by chemotherapy that could potentially shorten their life. It may even be less than that, but it’s about 1%. As far as chances of curing the cancer, myeloma’s tricky because we don’t think of it as a curable disease. What we’re doing is putting it into a deeper remission so that the cancer stays away for longer. And usually by transplant, in an average patient with standard risk disease, we can keep the cancer away for a number of years, maybe four or five years.

Compared if we don’t do transplant, it’s probably half as long, maybe two and a half years. Something like that. When we look at lymphoma, another cancer that we commonly treat with autologous transplant, we’re probably increasing, we’re doubling the odds of cure as an average guess doubling the odds or increasing the odds to about 50 50. It may not sound as good as patients want to hear, but I think without transplant, we consider it relatively uncurable and we need to use transplant to, to if the cancer’s proven to be sensitive to chemotherapy, I should add in that case, we can cure about 50% of relapse, large B cell lymphoma. So again, a 50% chance of cure with a very, very low chance of cure, otherwise in taking a chance of 1% risk of harm, highly in favor of doing transplants and large B cell lymphoma. And then as far as allogeneic stem cell transplant, it’s very individualized based on the patient, the donor and the disease becomes very difficult, but we talk about treatment related mortality, more on the more on the spectrum of 10 to 20%, and then the chances of cure again, highly variable. So too general to, to comment, I guess, without a patient in front of me.

Dr. Joseph Segeleon:

Well, thank you. Thanks for that. That’s a lot of very useful information. Now for our primary care physicians and providers that are listening. After the patient, the stem cell transplant recipient goes back to their community, are there specific things that the primary care provider has to watch for, has to be aware of?

Dr. Seth Maliske:

I think early post-transplant, we always worry about infection. That’s kind of the first, second and third thing on our minds, to be honest. If we can prove there’s no infection, we, a lot of times it’s just residual chemo toxicity and patients just need time to recover. Otherwise, can the stem cells cause harm? You know, a month or two down the road, generally not. There are some longer term chemo toxicities that are possible. The chemo can sometimes affect the lungs weeks or months down the road. So there are unique events, but for the most part, we worry about infection. Beyond that, I guess we always have to be concerned about blood clots, post-hospitalization and side effects of any subsequent medicines that we’re using. But for the most part, much of the toxicity happens in the first two to four weeks while they’re here in Fargo.

Dr. Joseph Segeleon:

I understand some of these patients will need revaccinated with vaccinations they’ve had in the past. Does that occur at the provider’s office, the primary care providers, or do they come back to the transplant center for those?

Dr. Seth Maliske:

So at least in myeloma, patients do get therapy to maintain remission afterwards. So if they’re seen by a cancer provider say in Sioux falls or Bismarck, Bemidji, et cetera, we have them restart this, what we call maintenance therapy with their local cancer providers. And we have them start the vaccines there. We help guide the vaccines and make sure that they’re done on time. So there’s communication with our nurse navigating team, as well as their teams locally. But for the most part, these vaccines do happen at their local offices. Perhaps, maybe the very first vaccine we do here, not because of risk or harm, but just because I always see patients at that six month mark, just to see how they’re doing. And that’s oftentimes when we start the vaccines, but it doesn’t have to happen with us here in Fargo. Ultimately my goal is to get people through transplant, get ’em out past that first 90 day window, and then try and return as much of their care as possible back to their local oncologists, who they garnered so much trust with before.

Dr. Joseph Segeleon:

  1. And so those, those patients do have some vulnerability to some illnesses that prior to the transplant, they perhaps did not. Is that correct?

Dr. Seth Maliske:

Yes, that’s correct. So when I was referencing much of the harm being in the first two to four weeks I’m not trying to describe the risk that their immune system is back to normal at the end of the first month. Really their immune system recovers over an extended period of time. So we have our innate immune system, which is neutrophils and something called natural killer cells. Those things recover first, and those are the things that prevent neutropenic infections, the infections that can really make people sick very fast. And those are the things that the most life threatening early post-transplant. So once those things are, once the neutrophils and natural killer cells are recovered, they’re much safer, but they’re not completely back to normal until closer to two years. And the reason why is because our lymphocytes, our B cells and T cells, they start to function more normally in that three month to maybe nine-month window. And so we delay vaccines until closer to six months. The vaccine schedule happens over a year and a half, actually, and so it’s not really until you’re fully revaccinated that your immune system really functions like it did prior to transplant. This ablative chemotherapy really wipes out our memory cells, as well as our normal innate immune system. And so we have to retrain it to protect against the against the infections that we can vaccinate against.

Dr. Joseph Segeleon:

Great, thank you for that. I know that the Roger Maris Cancer Center had been preparing for this program for quite some time. Tell the listeners the benefit of having a program like this in Fargo.

Dr. Seth Maliske:

So I kind of hopped on board after a lot of the heavy lifting was done. So I was amazed at what the team had accomplished in the years prior. So it’s – to build a transplant program, you have to have a huge team. You have to have a lab. You have to have an oncology program. You have to have an inpatient and outpatient program, and it takes a lot of work and a huge testament to the team at Sanford having built that. I started about a month or two prior to our first transplant. So I got to start really when all the heavy lifting was done. And so even in the last year, being here, it’s been remarkable to witness the stories that patients convey along the way. I knew of toxicity associated with transplant.

I knew of it a lot in the form of chemo toxicity and just how much time it takes to recover. But I don’t think I really appreciated just that, that toxicity of, of just proximity, that not just the time of recovery, but the time people spend going to and from doctor visits or the time people spend just traveling before transplant for the workup. That stuff, maybe I was aware, but become much more aware of as I’ve listened to patient stories over the last year. Patients are so pleased to be able to have their cancer care closer to home. It allows them to, I think, feel more comfortable, but not just comfortable being closer to home, but a lot of times their cancer doctors are other providers here in Fargo. I have a, a group of colleagues that are all malignant hematologists and they may treat the patient’s myeloma or the patient’s lymphoma.

Dr. Seth Maliske:

Maybe the nurses are more familiar. The nurses on the inpatient side become familiar. And then when we can do transplant in that same environment where people have already earned that, we’ve already earned their, their trust. That goes a long way as well. They’re not relocating, they’re not learning new doctors, they’re not learning new rooms. They, they just so feel, feel so much more comfortable just being at home. Now, of course, there are people that come from Bemidji and Grand Forks and Bismarck and surrounding communities. So not all of our cancer patients come from Fargo, but just having that familiarity is a huge aspect that patients appreciate as well. But yeah, I, I think, it’s truly remarkable. How, how appreciative patients have been of this program in just the first year of its existence.

Dr. Joseph Segeleon:

Yeah, I think very, very well put, I mean, the, you know, to have that trust in your environment to have the trust in physicians and nurses and hospitals that you already know, not to mention reducing the anxiety of the travel costs and all of the costs associated with travel and being away from home, it’s really an incredible benefit that we have within our community, a center like the Roger Maris center and the procedures and the cutting edge comprehensive care that you are providing, you and your colleagues. And I appreciate that it takes a team and there’s been a lot of foundational work that has brought you to the point that you are today. Why don’t we close up with two questions. Two questions I wanted to ask is maybe describe current state, what procedures you are currently doing, and then what does the future hold for your therapies and where you would like to see the program go?

Dr. Seth Maliske:

So we’ve spoken a lot about autologous, as well as allogeneic stem cell transplant. We’re well established with autologous transplant. We’ve completed a dozen or more transplants. I think the team’s doing a wonderful job and I look forward to continuing to do good care for autologous transplant. Allogeneic stem cell transplant will begin here in the fall. We’re not too far away, but it’s just a, it’s not just having the infrastructure, now it’s finding the right patient and treating the right disease. So I really expect that to – we’ll probably complete our first allogeneic stem cell transplant, sometime between October and December. I think we’re ready to go just about any time. We just have to find the right team in the right environment. And then as far as the future beyond allogeneic stem cell transplant, we haven’t discussed car T therapy a lot.

Car T stands for chimeric antigen receptor T cells. It’s just a genetically modified T-cell that is trained to fight cancer. We have a lab, we have all the foundation set up for that. We’re just kind of creating a a little bit more electronic medical record build and some education with nursing staff, but hope to bring that on board in early 2023. And then I think beyond just the technologies, I hope to bring a little bit more of a research infrastructure, more clinical trials. I would envision us being able to enroll kind of these advanced phase trials, you know, stage two, stage three, perhaps industry sponsored trials that really will support our patients with need for these cellular therapies such as stem cell transplant and car T therapy. So I think there’s a lot to look forward to, and I think the future is bright here in Fargo.

Dr. Joseph Segeleon:

That’s fantastic. And I certainly appreciate and have enjoyed the time we’ve had to talk about this. There’s great things that you’re doing up there for Fargo that you’re doing for the entire region and for Sanford. And I am looking forward to all that you are doing up there. I’m looking forward to learning more about this. I think it’s great that our patients, families and our providers know that there is this caliber of care that is close to home that we are comfortable with, that we know our colleagues and it really is a fantastic benefit for Sanford patients, families, and providers. So thank you again for your time, and I’m gonna turn it back over to Courtney.

Dr. Seth Maliske:

You’re very welcome. Thank you for your time as well.

Courtney Collen (Host):

Dr. Maliske, Dr. Segeleon, as always, thank you for joining us. This was another episode of our Called to Care podcast series by Sanford Health. I’m Courtney Collen. Thanks for being here and we will see you soon.

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