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Tiffany Kaczorowski: Welcome to Inside Pediatrics, a podcast brought to you by Children's Hospital of Alabama in Birmingham. I'm Tiffany Kaczorowski. Each September, we recognize Childhood Cancer and Sickle cell Awareness Month at Children's of Alabama. And today, we're talking with Dr. Matthew Kutny, who is an Associate Professor at UAB, the University of Alabama at Birmingham. He is also Director of the Leukemia, Lymphoma and Histiocytosis Program at Children's. Welcome, Dr. Kutny.

Matthew Kutny: Thank you for having me here today.

Tiffany Kaczorowski: So let's just get down to basics first. Why are these three diseases grouped together, as far as your program is concerned, leukemia, lymphoma and histiocytosis?

Matthew Kutny: That's a great question. So each of these diseases, cancers or serious blood disorders are associated with the blood or immune system. So leukemia is the type of cancer that derives or comes from the bone marrow and the immune cells that grow there. Lymphoma is very similar, but is involved in the lymph nodes, which are also a part of your immune system in various parts of your body. And then histiocytosis is a fairly unique type of a disease or a group of diseases that involves white blood cells, a particular type that there was controversy historically about whether they were actually a type of cancer. But with more modern technologies, we found that many of those disorders do involve changes or mutations in the DNA that really illustrates that they are types of cancers and each of these can be treated with similar types of chemotherapies.

Tiffany Kaczorowski: And then why specialize? Why have these disease-specific programs that we've developed here?

Matthew Kutny: So we put these together so that we can gain expertise in the clinical care and research so that we can provide the best care for our patients.

Tiffany Kaczorowski: I would imagine there are such incredible technologies and testing available now that we didn't use to have 10, 15 years ago. With these disease-specific programs, you guys are able to target a little bit better and tailor those therapies, right?

Matthew Kutny: Exactly. So as the understanding of the diseases become more complex, the evaluation and the treatment of them have become more complex. And that's really the impetus to specialize in these disorders so that the people involved really have the best understanding of them and can provide the best care. So, for example, when we say leukemia, that's a very general term. Leukemia involves a number of different disorders. There's B-cell leukemias, T-cell leukemias, and that's just a lymphoblastic leukemia, and there's also myeloid leukemia.

But within each of those, we've now understood that what really drives the cancer cell is oftentimes a change in that DNA, the genetic material. And we can evaluate each patient's disease individually using various clinical and genetic markers that help us understand that patient's disease the best so that we can provide that patient with the best treatment for their particular disease.

Tiffany Kaczorowski: And the fact that you guys are really working more toward it. I know a lot of research is involved in working more toward treatments that are less toxic to the body for these kids. And that produce less side effects down the road as they grow into adulthood.

Matthew Kutny: Exactly. Always our number one goal is to cure the most children with cancer, and that drives us each and every day. But we also recognize that the current treatment strategies, the chemotherapies that we use have a lot of side effects. So we also have a dual goal of curing children, but doing it in a safer and more targeted manner.

So the problem with traditional chemotherapy, we call it cytotoxic chemotherapy, so that means cell-killing. To kill the cell, what it does is essentially damages the way that the cell can divide, its DNA and its makeup. But it doesn't do that specifically to the cancer cell. Those same effects can happen to other cells in the body. And that's where we get the side effects, for example, the hair falling out. That's because your hair grows quickly and it damages those cells that are trying to go quickly and the hair falls out.

When we use things called targeted therapies or immunotherapies, we can start to get away from that non-specific killing or damage. We can now start to hone in and attack the cancer cells themselves.

Tiffany Kaczorowski: And explain a little bit more about that. Can you go into talking about how the body doesn't necessarily recognize the cancer cells like it would any other type of virus or the antibodies would normally, you know, kick into gear and help protect our body with other viruses, but not necessarily with cancer.

Matthew Kutny: Exactly. So of course this is a fascinating and quite complex area where, you know, we have this amazing immune system that is continually surveying our body to look for foreign invaders, bacteria, viruses, fungus, these other things, and it's highly effective in often treating those things. It actually does the same thing to try and prevent our own cells from becoming abnormal cancer cells. And in most cases, it can actually recognize a cell that's become abnormal and starts to grow and can kill it. But occasionally, these cells do continue to grow and evade this surveillance of the immune system and turn into a cancer.

So part of our strategies now are to help the immune system re-identify these cancer cells as something abnormal. And there are multiple strategies to that. You know, one of the initial and most basic ones was to use antibodies. So antibodies are a part of our normal immune system. They're kind of like magnets that attach to the outside of a cell on a specific target. And these are now developed to look for particular targets that are specifically on cancer cells. And you can give these antibodies so that they just attach to the cancer cell and then the immune system sees them and it kills the immune system. With time, that was also developed actually to be a way of targeting chemotherapy, so linking that chemotherapy agent to the antibody so that when it's delivered into the patient, it doesn't just go over the whole body and cause all these side effects. It really goes in and really just attaches and kills the cancer cells themselves. And that can obviously decrease the overall side effects and oftentimes can improve upon the cures, because we can do that in combination with other established treatments and chemotherapies that we already use.

Tiffany Kaczorowski: Another buzzword that we've heard a lot in cancer treatment is immunotherapy. We hear it here at Children's and in the adult world and the cancer treatment world. So tell us a little bit about that and how immunotherapy is being used.

Matthew Kutny: Right. So these antibody strategies are included in that overall terminology of immunotherapy, engaging the immune system in various ways. Other ways to more directly harness the immune system also involve a new type of antibody called BiTES or bi-specific T cell-engaging. It's a big word. But now think of basically two magnets hooked together. One magnet attaches to the cancer cell and the other magnet actually attaches to your healthy normal immune system cells, your T cells. And when it does that, it brings them into close proximity. And then your immune system cell, your T cell, sees that cancer cell and directly kills it. So it's a more effective way of really activating, harnessing, engaging that T-cell and your native immune system.

Building upon that technology, there's also been a big push to bypass the antibody part of it. Say, let's just work with those T cells that we know are so effective in killing the cancer cells. And we as a center are privileged to have a program in immunotherapy and cellular therapy that we can now offer something called CAR T-cell, which is chimeric antigen receptor t-cells, another big word. But basically, it means that we are able to take some of these T cells, the immune cells from the patient that are healthy cells and they are then manufactured or changed in a way that activates the T cells to directly recognize the cancer cells. And when they're infused back into the patient, they go in and survey throughout the body, going into any areas that have cancer and can help attack and kill those cancer cells.

Tiffany Kaczorowski: So you're taking healthy cells out, manipulating them in such a way that they recognize and then infusing them back into the patient, and then they go out and do their job.

Matthew Kutny: Exactly. So basically, you are making the patient's immune system treat the cancer like an infection.

Tiffany Kaczorowski: That's fascinating. How often are we able to offer some of these therapies? I guess it just depends on the type of cancer, where that child is in their stage.

Matthew Kutny: So we always want to build upon our prior successes and we want to maintain that good cure rate. So for some of the newest therapies, we first offer those to our patients who unfortunately have not responded to the normal or standard chemotherapies. So many of these immunotherapies or directed therapies started out by treating patients who had had relapses or refractory cancers and were shown to be efficacious, meaning that they helped cure those patients.

And once we see that signal through research studies, we then evaluate adding that new medicine or new therapy to the traditional treatments that we have used and have shown to be effective. And the only way that we can really scientifically know whether we're helping our patients is to do this in the setting of a clinical trial.

So the National Cancer Institute and us as a center, we are heavily engaged in research. And we've always said that the best treatments are to first establish what the standard of care is, what are the best effective therapies for a patient, but then to evaluate whether that patient may also be eligible for a clinical trial. And a clinical trial means that we are doing usually a smaller change in the established regimen, particularly in a newly diagnosed patient and comparing the established way of doing that with this small change. And then we evaluate how patients do. And it's a very systematic way of looking at these new therapies to see if we are curing the patients and we're doing that in a way that is less toxic. So we don't just only look at what patients are cured, but what side effects do they have? How are they doing with the therapy?

And particularly, for a lot of these immunotherapies, it's been very exciting because we're seeing that patients are tolerating them much better, that their experience going through that type of therapy, the side effects they deal with are far less than what they would have had going through some of the chemotherapy. And so very quickly, many of these immunotherapies are moving into the treatment of newly diagnosed or leukemias. And right now we have several open trials looking at these bi-specific T-cell engaging antibodies or these antibodies that are linked to a chemotherapy for some of our ALL patients, our acute lymphoblastic leukemia patients.

Equally important is not just the immunotherapies, but other types of targeted or directed therapies. So going back to the fact that we now understand that cancer is driven by these changes in the genetic material, the DNA, and we do a lot now to try and understand what is driving that patient's cancer.

And when we find that, we first try to figure out is there a targeted therapy? Is there an additional medicine that is going to help that patient and improve their cure rate above and beyond just giving them traditional chemotherapy. And so we have a number of standard approaches for that and also clinical trials that we can offer our patients using the newest and best types of treatments to help our patients with cancer and do so in a way that causes the least side effects. So our research programs, our clinical trials are very important to the work we do and to the service that we can provide to our patients.

Tiffany Kaczorowski: And not only to our patients here in Alabama, that they don't have to leave here for those clinical trials. Explain how the impact that we have here not only affects the children in Alabama and in neighboring states who come to us, but then also affects, you know, children nationally going through a treatment.

Matthew Kutny: Definitely. Well, I am privileged to work here with an amazing group of physicians and nurses and everyone. And we are very active on the national stage. So just looking at our program since that's the focus today, my colleagues are all involved in types of research that are really advancing the treatment of these diseases at a national level.

So just briefly, for example, Dr. Julie Wolfson, one of my partners, she's involved in a national clinical trial chair and looking at ways of best treating adolescents and young adults, called as the AYAs because there's always been a lot of focus on children with cancer and then elderly adults who have the highest rates of cancer. And unfortunately, these folks in the middle, the adolescent and young adults have often been left out of research strategies and they really lag behind in improving cure rates in the last decades. And Dr. Wolfson in particular with others is really trying to advance the treatment for that group in particular.

Another example, Dr. Ana Xavier, she is a leading researcher in lymphomas nationally, and also clinical trial chairs for particularly difficult to treat types of lymphoma and really targeting those so that we can advance the cure rates. Also, Dr. Aman Wadhwa is focusing on more of the supportive care and outcomes. So not just a cure like we're talking about, but doing that in a way that minimizes side effects. And he's trying to understand what are the patient factors that really impact or can predict who's going to have more toxicities with their treatments. And then I, myself, I'm focused in leukemias, particularly myeloid leukemias and have been a study chair for national trials in that regard.

So here at Children's of Alabama and UAB, you have folks who really understand the national spectrum of what's going on and what treatments we can provide for our patients and also driving some of that research and innovation. So it's a very exciting place to work and certainly a wonderful group to work with.

But it's not just about the physicians who are doing the research, we are a team. And that team is inclusive of a whole group of amazing people. We have nurse practitioners who really are important for our patients and engaging in their care and helping the family through this journey. We have nurses who are in our clinic and over on the inpatient unit who are expert in delivering chemotherapy in all the supportive care that goes into that.

And really when patients come in, they become a part of the family and get to know these nurses because they are unfortunately having to come to the hospital quite often or come to our clinic, visits on a very regular basis.

Tiffany Kaczorowski: Right. It becomes their second home.

Matthew Kutny: Exactly. You know, for many people, when they see the doctor, it's sort of a once a year thing. But for these kids, they're coming very frequently. So they really become a part of our family. And with that comes a lot of burden for the family, that they are going to be missing work. It's a financial stress. So we have social workers, child life experts, and all these other folks who are involved in making that process as seamless and bearable as possible. So that it's a good experience for the family and for the patient. And it's been quite amazing to see that team in action as I've been here over the last decade.

Tiffany Kaczorowski: I do want to go back and talk, you know, historically speaking, you've talked about before, how through the years, the therapies and the treatments and just the specialization of your field, everything is just becoming so much more precise. Can you kind of give us some perspective, you know, maybe 10, 15 years ago versus now?

Matthew Kutny: Exactly. I think that's an excellent word is that we want to be precise in our treatments because we not only want to, you know, give medicines that we know can kill cancer cells. And that was the first kind of era of chemotherapy and pediatric oncology was, you know, finding medicines that would just kill the cancer cells so that we could cure some patients. Over time, that became more specialized using multi-agent chemotherapy, finding the right mix of medicines that would do the best job in killing these cells. In fact, we would even incorporate things like radiation therapy to treat disease that was around the brain and spinal cord. But knowing that those really had significant effects on neurocognitive function, their brain activity long-term.

So now, we're at an era where we have been able to improve those cure rates to a point where we can start thinking about how can we do this better with less toxicity. So making those changes to remove certain more intensive and toxic treatments, adding in these directive therapies that really target the changes in the cancer cells, so that it's not affecting the other healthy cells using the immune system in a way that can completely replace in some cases some of the chemotherapy agents and give a much better experience to treatment for the patient and their families. That is our goal. And we're going to continue to fight for that every day here at Children's of Alabama and UAB.

Tiffany Kaczorowski: Awesome. Also, I know you wanted to mention the support of the community. So we obviously have a big team, a huge team, you know, 300 plus staff members and doctors and nurses who are working here at Children's and UAB to support these patients. But then also the outlying community, you guys have felt so much support from them through the years.

Matthew Kutny: Absolutely. What we do, being precise, having complex treatments, having this whole team of people to support the families, that takes a lot of resources, you know. But we want to provide the best for the children of Alabama. And to do so, we have relied upon the community support and the community has been amazing in engaging us and supporting us through that so that we have the best folks here to provide the best therapies and that patients don't have to travel to other places, that we're always expanding, providing new types of research and new types of treatments, the best facilities, the best diagnostics, those are the tests to evaluate things that we are really privileged in Alabama to have a community that embraces what we do and supports that.

Tiffany Kaczorowski: Thank you so much, Dr. Kutny, for joining us today.

Matthew Kutny: Thank you very much.

Tiffany Kaczorowski: Thanks for listening to Inside Pediatrics. More podcasts like this one can be found at childrensal.org/insidepediatrics.