Ep. 10: Blood and bone marrow transplant care at Sanford

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

Episode Transcript

Courtney Collen (Host): Hello and welcome to our medical series Called to Care by Sanford Health. I’m Courtney Collen with Sanford Health News. Called to Care brings forward medical experts who give fellow clinicians advice and guidance that they can use in their primary care practice and information about when it’s time to refer patients and families to more specialized care.

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This is a really special episode because in October 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 to treatment. To tell us more about it is Ammar Alzoubi, M.D., a medical oncologist specializing in cancer and blood disorders. He is the director of Sanford’s Blood and Bone Marrow Transplant Program. Leading this conversation with me is Joseph Segeleon, M.D., who is a leader in pediatric critical care here to help us dive even into these topics to provide the best insight for our clinicians, patients and communities.

Dr. Segeleon, welcome. It’s good to see you.

Dr. Joseph Segeleon (Host): Thank you, Courtney. It’s great to see you again, as well. Well, I’m really excited about today’s podcast for our referral physicians and providers. I have Dr. Alzoubi here. I’m just very excited to learn and more about this. Dr. Alzoubi, welcome.

Dr. Ammar Alzoubi: Thank you so much.

Dr. Joseph Segeleon: Oh, it’s really great to have you, and we’ve had some really interesting podcasts and this is exciting because we get to talk about a service that is brand new to the Sanford enterprise. So I’m very happy to have this opportunity, I think, to just start off, who would benefit from this new service that you have?

Dr. Ammar Alzoubi: So a lot really of patients who have hematologic malignancies in particular myeloma leukemia and lymphoma. The indication for either autologous marrow transplant or allergenic bone marrow transplant is applicable mainly on those three groups of patients. However, the same transplant, especially autologous bone marrow transplant can be applicable for rare cancer, such as germ cell tumor or what we call testicular cancer and also on autoimmune disease patients who have severe lupus, sometimes that transplant can be indicated, but those are rare indications mainly for leukemia, lymphoma and myeloma.

Dr. Joseph Segeleon: OK, great. And just so we sort of level set, when we use the term bone marrow transplant, I know we’re really talking about stem cells, but also just for our audience, just to kind of explain the terminology, bone marrow transplant autologous allogeneic, if you would please.

Dr. Ammar Alzoubi: Sure. So bone marrow transplant is really, this is the old name we are using. So in the old days, back in 1940s and 1950s we harvest the bone marrow from the bone marrow and we freeze it and we infuse it back. And that’s what the name come bone marrow transplant. But what we are really doing, we are collecting a stem cell, but we use to collect all the bone marrow. So this name over time in the last 20, 30 years changed to a stem cell transplant because now we have ability to collect only the stem cell stem cell from the peripheral blood. So we a patient’s medications to stimulate those stem cells, which is the primitive cells make all types of blood count to increase in number and to get mobilized or move from the bone marrow to the blood stream.

And we put the patient on a machine called a apheresis machine, and this machine circulate the blood from the patients to the machine, the machine collect only the stem cells and return everything back. So we collecting a stem cell, so now becoming stem cell transplant, but we sometimes still use the old form bone marrow transplant. In fact, in adult, more than 90% of adult stem cell transplant, so collecting the stem cell from the peripheral blood. In pediatrics, still around 50% of them still get the old fashioned bone marrow transplant. So for the audience, I will say bone marrow transplant and stem cell transplant is same terms. We use them almost the same of auto transplant and allogenic bone marrow transplant. Auto is referred when we re take the bone marrow or the stem cell from the patient, and we return the same stem cells to the patient.

And this is really a way of giving high dose chemotherapy. That’s all. A high dose chemo patients will not able to tolerate otherwise by taking the stem cell in it, in the freezer, we are able to give high dose chemo, and we rescue the patient by giving the stem cell back to make a blood count. That is an autologous bone marrow transplant. The allergenic bone marrow transplant is very different. We get the bone marrow or the stem cell from a donor can be a relative or somebody unrelated or even cord the blood. We match the genes or the cells to the patient, the patient, most of the time have some certain type of leukemia rather than myeloma. And those patients get to treated before the transplant. And when they get the transplant, they get really a foreign cells to them, foreign stem cell, those stem cells, or the new immune system infused from other person work against the cancer or against the leukemia. And we have a special term for it. We called it graft versus leukemia. So a bone transplant treat the cancer by the providing immunity or the immune system of the donor, recognizing the cancer cells while the former transplant is really a way to give high dose chemotherapy.

Dr. Joseph Segeleon: OK. So thank you. That was, that was very helpful. Let’s take an autologous transplant. Why don’t we walk through the process for a patient. So take a given patient with malignancy. Walk us through the process of choosing when you get the stem cell the process pre post and what happens to the patient up at the, the, the medical center?

Dr. Ammar Alzoubi: So let’s take patients with myeloma and that’s the most common indications for autologous bone marrow transplant. When the patients get diagnosed with myeloma, the first step is to receive a treatment to decrease the volume of the cancer cells. And what we call this, we call it induction therapy, has nothing to do with the transplant process. After we reduce the disease almost to nothing or to a very small amount, the bone marrow transplant process start. The bone marrow transplant goes in three steps or three phases. Phase one is collecting the stem cells phase. Number two is the actual transplant and phase number three is recovery. In phase number one with, as we call it mobilization the patient is first get pretesting. We check their heart, their kidney, their lung, make sure everything is normal, and they will tolerate the transplant and the high dose chemo in mobile during mobilization, the patients receive a medication under injection under the skin for roughly around five to seven days.

And after four to five, seven days, we check the stem cells in the peripheral blood to see they are adequately high. And if they are high, they goes on the apheresis machine to collect those stem cells. The patient stay on the apheresis anywhere from three to four hours, sometimes one day 50, 60% of patients. One day, some patients need two or three days collecting the stem cells to collect enough. We collect anywhere from five to 10 million cells per kilogram. So we collect good amount of cells.

And after we collect enough, the patients is done. Phase one, those cells go to the lab. We process the stem cells. We put it in a small bag and we freeze them. Around two weeks later when the patient recovered from the first treatment that the actual transplant, the patient get admitted, some center do the auto transplant as an outpatient during the admission in one day or few days, depend on the type of the cancer they have, they get high dose chemotherapy. Literally within 24 hours after the chemo is done, we infuse the stem cell. We thaw them, we put them in a warm bath, warm water. We thaw the cells, or we thaw the stem cells and the patient receives their stem cells back. And this process take like a blood transfusion. This process take around five to 10 minute for each back. So in 10, 15 minute, the transplant is done now because of the chemotherapy, the patients will have very low blood count, high risk of infection. They receive antibiotics.

Roughly 12 to 14 days after we give the stem cells back recover, or the marrow recover, the patient start getting white blood cells, red blood cells, and platelet. Their immune system start to recover two to three weeks after the chemotherapy. And after the transplant, we send the patient home. Their full immune system, recovery may take up to six months to a year, and that’s really the recovery period. The recovery period is watching the count to go back to normal and watching the patients. If we develop any infection, we give them antibiotic to prevent infection. Really the last step and can’t all part of recovery, because of high dose chemo, the patients lose their immunity to childhood disease or all the disease they get exposed to. So six months after the transplant, they start getting vaccination, childhood vaccination, like diphtheria, mumps vaccinations. We will repeat all their vaccination within a year and a half to give them the immunity which they lost during the transplant.

Dr. Joseph Segeleon: Is the cell work done here at your center?

Dr. Ammar Alzoubi: Yes. And that’s what, really something that we are very proud of. We decide to be build the stem cell lab, meaning we decide not to ask a company to come get the cells, which we collect and give us the sales back. So yes, we build a stem cell lab. So when we finish ASIS and get the stem cell lab in the back, it goes here to Sanford lab here in, in Broadway Fargo. And the, we hire a clinical pathologist just who oversee the stem cell lab. He process the cells, freeze them in the right way. And that’s all by the way FDA mandate on how we supposed to do that. And we are in compliant with all the rules. So yes, everything’s done here at Sanford.

Dr. Joseph Segeleon: Just fantastic. I think we are so fortunate to be able to have those resources within our system. Now I understand the engraftment process now is do the, does the patient have to stay close to the medical center during a certain period of time of treatment?

Dr. Ammar Alzoubi: Absolutely not. Only they have to stay. So even center who do it, OPO transplant as an outpatient, they ask the patients to stay in the city of the center for roughly three to four weeks minimum. And sometimes that can be extended to months. So the patient will stay in the hospital between two to three weeks, but after he leave, he’s supposed to stay in Fargo area for another one or two weeks until we make sure he’s safe to go back home. Not only the patient have to stay in Fargo, he has to come with a caregiver. So we ask for a caregiver to accompany the patient during the transplant. And also the caregiver has to stay in the city where we do the transplant.

Dr. Joseph Segeleon: Thank you. So, let’s take a patient with myeloma. What complications are you looking for perhaps early on or later for our listeners?

Dr. Ammar Alzoubi: Sure. The complications mainly related to the high dose chemo we give. As I mentioned before, the dose of chemo is a fatal key dose meaning without a bone marrow transplant, nobody can survive the chemotherapy. We give, we have a saying in the transplant group, we say we can’t kill the patient and we’re bringing them back. So all what I mean that, but doesn’t mean is not safe. It’s really safe, but complications can happen. So chemotherapy complications, mouth soreness, something we call a microsites can be very severe, all risk of infection, pneumonia, blood infection, and rare complications of lung damage. As a result of chemotherapy, majority of patients really stay in their room. They have some symptoms and they recover the moment, the count recover, however, maybe around rough two to 7% of patients may get very sick and require intensive care unit admission and mortality rate losing the patient as a result of the OGO bone marrow transplant, roughly now between all 0.5 to 1% only. So we are mortality rate is really low from auto transplant. While in ALO met mortality rate can be higher. So the complications again is mainly infection. Organ can damage as a result of infection or antibiotic. We give there’s a rare complications. We really don’t see, we call it the graft failure. So the stem cell we are giving does not grow in the body and the patients to need to have low blood count. Unfortunately, those patients either require another transplant or they may actually, all this may result in death.

Dr. Joseph Segeleon: So the survival rate, if I heard you say for the patients at one year is quite high for the autologous patient.

Dr. Ammar Alzoubi: Exactly. The survival rate, actually there we call actually we have got the survival in two different way. There’s survival limited to the disease and survival related to the transplant. So the way we say it in the transplant is what we call 30 day survival and like a year survival. So in auto transplant 30 day survival and one year survival is almost identical. If we don’t lose the patient in the first 30 days, we don’t lose the patient a year later due to transplant. This is survival related to the transplant or transplant related mortality. So mortality in auto transplant is 0.5 to 1%.

Dr. Joseph Segeleon: Obviously this is a great moment for Sanford. And having this in the enterprise really gives us, and our patients, the opportunity to take care, take advantage of these resources and the expertise of you and your team close to home. Can you talk a little bit about the benefit of having a program in Fargo?

Dr. Ammar Alzoubi: Absolutely. I’ve been here in Fargo now for almost 10 years, and obviously I’m seeing a lot of patients with myeloma and leukemia for that period of time. And we send a lot of patients down to Mayo Clinic in Rochester or university in the Minneapolis and actually the burden on patients and patients, family of driving minimum three and a half hours. And up to eight hours, if somebody live in northern Minnesota, it is, it is really like if you speak with patients who went through the transplant, one of the more things they hate is driving all the way that drive, which they usually not just one visit. They have to live there for six weeks. Some people have to arrange an apartment. The caregiver has to leave their job as well to be with, with them. So some patients get complication and they have to go to Mayo every two weeks with this drive. So having this service here in Fargo is definitely ease the burden of at least the trouble and having this service here, which is in my opinions needed long, even more than now, just this set has to be provided here. In fact, if you look in the United States, I don’t believe any area in the U.S. patients have to drive six or eight hours for transplant. Most of the transplant center within much shorter driving distance.

Dr. Joseph Segeleon: It must be quite satisfying for you over 10 years to see your efforts come to fruition.

Dr. Ammar Alzoubi: Absolutely, absolutely. In fact, today, one of my patients say, ‘oh, I saw you on the TV.’ And I said, ‘yes, I am very proud.’ It’s not only me, the whole team at Sanford. We are really proud that we able to accomplish what we did now.

Dr. Joseph Segeleon: Let’s talk a little bit about the patients who are referred to you. I’m assuming that patients are referred to you then through oncologists, is that correct?

Dr. Ammar Alzoubi: Exactly. Right. So here, we obviously our own patients or patients who come in the, from the time of their diagnosis, we take care of them and we don’t have a referral, but now things we have this service oncologist, all like in North Dakota, Northwestern Minnesota, they will diagnose the patient, initiate the therapy and then communicate with us and refer the patients for the transplant because the service not available there. In fact, we already see that we are getting referral from the group and we getting referral from Bismarck.

Dr. Joseph Segeleon: OK. Now I understand right now doing predominantly autologous and malignancy, what does the future hold with regards to the program and the direction you would like to take?

Dr. Ammar Alzoubi: Sure. So our plan is really to have a full service transplant and cellular therapy. This is the other name of the transplant. So after having around 10, 15 auto transplant, and that’s probably will happen by the summer of, or the fall of next year, we are planning to start doing Allogenic “allo’ transplant. Allo transplant has different types related from a brother or sisters, unrelated and from cord blood and something called haplo from children or parents. So we will be doing Allo transplant starting in the summer, or end of the summer or fall of 2022, by the end of maybe middle of 2023 or spring of 2023, we going to start doing what we call cellular therapy or CAR-T. This is a very advanced immunotherapy. When we it’s like a transplant, we are harvesting the immune system to kill the cancer cells. So we will harvest certain cells instead of harvesting everything and including the stem cell, we harvest only certain immune cells, something called ink cells, natural killer, or T-cell lymphocyte. We harvest those cells. We manipulate the cells, or we teach them to fight or to attach to the cancer cells. We grow those cells outside of the body. And usually there’s a pharma company who do that. Then we infuse the cells back to attach to the cancer cells and kill the cancer cells. And this mainly applicable right now for lymphoma, but we expect in the next five, 10 years, the same therapy will be applicable for multiple different cancers, including solid malignancy. And this cellular therapy will be also part of the bone marrow transplant here in Fargo.

Dr. Joseph Segeleon: Yeah. That that’s CAR-T cell therapy is just incredibly exciting and just, it’s really fun to think about those services being offered here in the region. Will the future also hold some patients perhaps that have different types of anemia or inborn errors of metabolism or other autoimmune diseases?

Dr. Ammar Alzoubi: I think when the program mature, and I think the program will mature in roughly three to four years, we expecting to do roughly around a hundred transplant between auto transplant and probably 40 or 50 of cell therapy. What I’m trying to say when this, when the bone marrow transplant mature and providing all type of transplant, then whatever available for other diseases, either met metabolic disease or red blood cells disease. Then it will be also offered here. We will not have limitations. The only limitations will be is really the pharma who making the drug or making, having the technology. So the answer yes, but is really unknown at this point.

Dr. Joseph Segeleon: When I understand there’s a team that is involved in this endeavor, can you speak a little bit to you know, how big is your team and, and who, what comprises the team that makes up who can do this service?

Dr. Ammar Alzoubi: I am going to say is not a team, it is an army.

(laughter)

Dr. Segeleon: Very good.

Dr. Ammar Alzoubi: Even before we start the transplant, two years before we start the transplant, we have administration construction service to build the stem cell lab finance patients from the finance, from insurance, seeing physicians, all of those laws involved in the two years before even we opened our door for the first transplant. And as of now the same team really still involved, mainly we have physician nurses, bone marrow transplant co-coordinators, which is a nurses work, a bridge between the patient and the medical team. We have psychologists, nutritionist patients who actually, sorry, individuals who work with finance and insurance and the administrations to continue supporting the growth of the program.

Dr. Joseph Segeleon: Yeah, you were right. It is an army. As we close up today, is there anything that I haven’t asked you that you would like to comment upon?

Dr. Ammar Alzoubi: Everyone who was involved. In particular, I want to thanks our patients who put the trust in us to start our first or second transplant. And I really want to thank the administration because the efforts and the finance they put on it is definitely great. Without it, we will not be able to have this service here.

Dr. Joseph Segeleon: Well, great. Well, Dr. Alzoubi, it was really nice talking to you and thank you for all that you do for our patients and our communities in the region and for what you do for Sanford. I’m located in Sioux Falls and we’re quite excited to hear about the program and are excited to participate as well.

Thank you again for your expertise.

Dr. Ammar Alzoubi: Thank you so much for having me, I really enjoyed it.

Courtney Collen (Host): Dr. Alzoubi, Dr. Segeleon, thank you. This was another episode of our Called to Care podcast series by Sanford Health. I’m Courtney Collen. Thank you so much for being here. We’ll see you soon.

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