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Dr. Sibo Zhao takes us on an exploration of new, novel, treatments and research in pediatric neuro-oncology. She also brings into focus the added complexities in brain tumors in children and how those complexities both challenge and benefit what physicians are learning in order to improve treatment.

Meet Dr. Zhao

Related information

Neuro-Oncology

Oncology

Fertility Preservation

Life After Cancer

Hematology and Oncology

Clinical Research

Transcript

00:00:03 

Host 

Hello and welcome to Cook Children's Doc Talk. Treating brain and spinal tumors can be extremely challenging, especially in children. But there have been many breakthroughs in pediatric neuro oncology with more new advancements on the horizon. Today we're talking with Dr. Sibo Zhao, about what's happening in this field. Dr. Zhao is medical director of Cook Children's pediatric Neuro-Oncology Program. She is actively involved in research here at Cook Children's and has written extensively on this subject. Not only is she dedicated to advancing treatment, she is also passionate about how care is delivered to patients and their families as they go through treatment. Dr. Zhao, welcome. We appreciate your taking the time to talk with us.

00:00:46 

Dr. Zhao 

Thank you for having me today.

00:00:48 

Host 

So first off, can you give a little history on yourself? What drew you to the practice of pediatric neuro-oncology?

00:00:57 

Dr. Zhao 

Well Jan, I think throughout my medical trainings, I feel like I've always been drawn to help the vulnerable patient population. You know, that's kind of how I chose pediatrics in the first place, because I felt like the kids, you know, they can't advocate for themselves, they needed more help. And then during residency, oncology would be something that would feel rewarding, because again, those are the kids that need more, and I was drawn to that. So I went to the hemonc and I kinda was wide open thinking like, okay, I want to do oncology, and really sure what kind of tumors are necessarily even needed to pick one. But during fellowship, and during just kind of my early career, I think the brain tumor patients just always kind of tapped on my heart a little bit. And I wanted to do a little bit more for them. And also, the other main thing is that pediatric neuro oncology has not really advanced as fast or as quickly as some of the other types of pediatric malignancies such as you know, leukemia patient outcomes, I felt like there was a need. And this may be something that if I went into that field, I could change that.

00:02:10 

Host 

So why did you choose the program at Cook Children's? And how does your research background fit in with your role here?

00:02:16 

Dr. Zhao 

So I spent several years at Texas Children's Hospital first as a trainee and then became a faculty, I honestly didn't really think I would like any other places or want to go away, but I knew deep down that I was just more than prepared, you know, I was very well trained. And I could go on and take on a different type of role or different programs. So I just thought, Okay, I will look around and see so I went and interviewed at several larger children's hospitals and their programs all felt, you know, pretty similar to Texas Children's and, and then this opportunity came up here at Cook Children's, and I came and was pretty much immediately just blown away. I think the culture here was very refreshing to me. And the philosophy here, I've just really kind of fits with what I wanted. And my beliefs. And I'm very glad I joined, I think is probably one of the best decisions I made. As far as research, I think, I realized that the hemonc program here at Cook Children's had a very heavy focus on clinical research, which is what I want to do. So in that regard, transitioning here from TCH to Cook Children's, and being able to continue to do clinical research just makes sense.

00:03:34 

Host 

What's the difference between pediatric neuro-oncology and adult neuro-oncology? And how does that impact the treatment of children?

00:03:42 

Dr. Zhao 

Probably first and foremost, despite that, they have the same names. You know, we may have kids and adults that both have glioblastoma for example, we know that the biology are very different between the pediatric brain tumors and the adult brain tumors. By this I mean that they can have the same name, but they may have different mutations, they behave differently. They have different outcomes. So they're just different. I think we always tell our families and we've been trained that you cannot just apply, you know, what's been done to the adult brain tumors the same way as pediatrics. I think the other thing that's really, really important to know, as far as the difference is that treatment options usually lag behind for kids, sometimes by a decade or more, which is unfortunate. And that's not just for neuro-oncology, that's for all pediatric oncology patients. The adult oncology, they receive more research funding, there's more robust pharmaceutical support in drug development. They get more FDA approvals for new agents, and so I think the treatment for them is far ahead compared to the treatment for pediatric patients.

00:04:58 

Host 

Brain and spinal cord tumors in children are so complex and very difficult to treat, what factors contribute to this?

00:05:05 

Dr. Zhao 

Yeah, so the main thing is just there's so many different types. You know, people always talk about CNS tumors or Central Nervous tumors or bring our spinal cord tumors, kind of as a group. But really, there are at least the last time I checked more than 120 different types of brain and spinal cord tumors. And that list of diagnosis are still changing and growing. So I think it says a lot about the complexity, you know, we are now reclassifying tumors, not only by the histology, but also by molecular information are integrated into that. So it's shifting over the last five years or so. And we are constantly being updated on what is this new entity, what this type of tumor is. So it's complex, because there's so many different types, and there's always something new that are being discovered, and that we have to learn about. But I think, in a way, the complexity helps us because it helps us, you know, make better diagnosis, it helps us design better treatment plans, or even give better prognosis for families, as far as you know how I think you will respond to this treatment based on you know, this marker or that. So it's complex. But there's a reason why I think the complexity is very important to really fully understand for us to help you know, these kids.

00:06:30 

Host 

How does the child's age affect how tumors behave and how they respond to treatment?

00:06:36 

Dr. Zhao 

I don't think the age in itself really affects how the tumors behave. I think certain types of brain tumors are more common in the age group. You know, some tumors are more common in infants, and some we'll see more in older kids. So any differences in outcomes or behavior is probably still more related to the tumor types than just their age. For me, the most important factor related to age is how the treatment will affect that child's neuro cognitive development in the future. For example, we don't offer radiation therapy to young children, because we know the younger they are, the higher the risk there is for them to have neurocognitive deficits in the future. That's the most important thing that age plays in to the treatment decision for me for the brain tumor patients.

00:07:29 

Host 

Dr. Zhao, what treatments and care are currently available for children with brain and spinal tumors?

00:07:35 

Dr. Zhao 

So Jan, that is a pretty broad question. In summary, it's a team effort, most of these kids, usually will need some sort of surgery, whether it's a biopsy, or resection to help us make the diagnosis. And following that, depending on what the diagnoses are, they may need chemotherapy, or they may need radiation or they may just be observed. So there's a wide range of treatment, depending on what we're treating.

00:08:04 

Host 

Some tumors, for instance high grade gliomas, have very poor outcomes and are nearly impossible to treat, what hope then might be on the horizon for getting ahead of such deadly diseases.

00:08:16 

Dr. Zhao 

These are very difficult cases. And that includes our DIPG patients as well. The pediatric neuro-oncology world, I mean, all of us who take care of these patients are moving as fast as we can. There are numerous clinical trials out there. Some are targeted therapies, some of them, you know, use the immune system to attack the tumors. Some trials are designed to deliver the drugs closer to tumors, so people are looking at all different ways and what we can try what's innovative, that can maybe bring us new treatment options. You know, we are actively researching and really just desperately hoping that we can find something to improve the outcome for these terrible, terrible diseases.

00:09:02 

Host 

Neuro-oncology, and especially pediatric neuro-oncology is an ever evolving field. In what areas is medical science currently showing the most success, especially for children?

00:09:14 

Dr. Zhao 

We certainly are learning more and more about pediatric brain tumors at a very rapid pace. In the last five to 10 years, the amount of molecular information kind of just exploded. I think through genetic and epigenetic studies, we now understand a lot more. For example, we know that not all medulloblastomas are the same. We now know why some children do well and why some children don't with the same diagnosis. So in a sense, I think a lot of our success so far is related to gaining more knowledge about these tumors, but the next step will be translating those knowledge into some successfully improved outcomes in the future.

00:10:03 

Host 

Are there any promising clinical trials available?

00:10:06 

Dr. Zhao 

Yes. We have recently opened two new clinical trials here at Cook Children's for patients with low grade gliomas. And these two trials are very similar. The only difference is that one trial is for a patient with neurofibromatosis type one, and the other one are for those without that diagnosis, but both are geared toward low grade glioma patients. The trial are studying this town pound or drug selumetinib. It's a MEK inhibitor. As I mentioned earlier, through research, we have known for a number of years now that all pediatric local gliomas are affected by a similar molecular aberration. And this drug selumetinib is a medicine or compound that targets that pathway. So there's just a lot of excitement within this field, in that maybe one day in the future my new patients with newly diagnosed lower gliomas maybe offer a pill that they can take at home instead of having to come in for their IV chemotherapy infusions, and blood counts and all of that monitoring visits. So these trials specifically are comparing the selumetinib with the commercial IV chemotherapy and hopefully be able to draw some conclusions. You know, we also have opened up two new high grade glioma clinical trials here at Cook Children's. Both of these, again, are molecular driven, targeting certain mutations that are commonly found in high grade gliomas. So I think the field is generally moving in that direction for sure.

00:11:45 

Host 

Trials like that could be real game changers for these kids, especially the idea of taking a pill at home as opposed to having to go through chemo.

00:11:52 

Dr. Zhao 

Absolutely. I think the excitement is there, the parents, the patients, and all of us who treat these patients, we're all hoping that's where we're headed. But we're not quite there yet. And these ongoing clinical trials will give us that information or validation of what we think will be the new option for them.

00:12:12 

Host 

What are the factors that determine whether a child should be involved in a clinical trial or qualifies for a clinical trial?

00:12:19 

Dr. Zhao 

We are a very clinical trial heavy hospital, meaning that the neuro-oncology program would offer clinical trial to every patient who is eligible. Now there are certain diagnosis or certain factors about their diseases or their diagnosis that make them not a candidate for a clinical trial. But as long as a child is a potential candidate, we offer trial options to all families. And it's a consent process where the family have to understand that the participation is voluntary, that a clinical trial helps us improve our future treatment options. But there's always a risk of not knowing if the clinical trial option is just as good as the center of care. But we feel it's very important to offer those and for families to participate. And we appreciate their participation.

00:13:11 

Host 

One of your key goals is bringing developmental therapeutics to Cook Children's as well as anti cancer care, can you give us some details on that?

00:13:20 

Dr. Zhao 

So developmental therapeutics is an effort to help both in facilitating the discovery and the development of any new cancer therapeutic treatment options to patients. So in the past, my focus on developmental therapeutics involved testing novel compounds in mice. And now these are mouse models that developed brain tumors after they were injected with brain tumor tissues from our patient, who graciously donated samples. And these kind of experiments really aimed at finding preclinical evidence that a compound is effective, therefore, we may be able to bring them to human trials. So that's kind of what we call translational research, you know, bringing treatment options from the bench side to the bedside. So now, I obviously don't do those kinds of experiments anymore, but I really value the experiences I had in the past. But researchers like myself can continue to contribute to developmental, therapeutics and other ways. And conducting ongoing clinical research is also part of that spectrum of bringing the best treatments and developing new drugs. And that's what I do here. And I am very passionate about it and I hope to bring more and more options to my patients.

00:14:46 

Host 

How do you see developmental therapeutics changing treatment of children, teens and young adults with brain and spinal tumors?

00:14:54 

Dr. Zhao 

I think it will lead to more options. Hopefully, less toxic treatment options, and hopefully improved outcome.

00:15:04 

Host 

How many children does the neuro-oncology team see on an annual basis?

00:15:08 

Dr. Zhao 

We see on average about 80 to 100 new diagnoses per year. Now, not all of them require full-on treatment, meaning that not all of these kids need surgery or chemo or radiation. But these are the ones that we diagnose. And we follow.

00:15:28 

Host 

Can you talk a little bit about some of the most difficult cases you see?

00:15:32 

Dr. Zhao 

Um, unfortunately, there are so many. And I tend to carry a lot of these cases and memories with me. So I think for me, it's not the treatment decisions that are difficult or helping them go through their therapy that's difficult. It's more just the emotional component. That's really difficult. For example, I remember during my pediatric neuro-oncology training, I took care of a little boy with a pretty aggressive form of medullablastoma, and his tumor came back before he even finished treatment, which is suggestive of how aggressive it is. But this family was going through a lot more than that, because his mom had terminal stage four breast cancer. So they were going through this simultaneously. So his mom was not able to be in the hospital with him when he passed away. And I remember sitting with his dad, just him and I, in ICU, you know, for a couple hours or, you know, during the last few hours of his life, and his dad sang, "You've got a friend in me," from Toy Story Three, which is their favorite movie. And to this day, I can't listen to the song, you know, without thinking of him or, or getting teary eyed.

00:16:59 

Host 

It has to be really, really challenging to not get emotionally involved.

00:17:06 

Dr. Zhao 

It's impossible.

00:17:10 

Host 

So what support programs are available to neuro-oncology patients, and maybe even families at Cook Children's?

00:17:18 

Dr. Zhao 

Oh, there's many so many awesome support programs here. I think what kids love the most are visits from the therapy dogs. We have a camp, called Camp Now, that we host every September. It's a weekend camp, we invite our patients and families. And so that's a popular program that our kids love. The other things like, you know, Child Life and social workers, and, you know, they're always here to support our kids. For the teenagers. We have the AYA or Adolescent and Young Adult program that we offer the option to participate. Some are not willing to participate. But some teens find that really helpful. You know, we also talk to them about fertility preservation, which is very important for our older patients, there ar a ton, I think the list can go on and on.

00:18:07 

Host 

It must be extremely difficult to deliver those diagnoses to patients and families, what is your approach to helping them understand the condition, the treatment options, and prognoses?

00:18:19 

Dr. Zhao 

There's not a set way to do this. And I think every oncologist has his or her own ways, I think it's impossible to prepare a set dialogue, because every family is different. So I think over time, you just kind of develop the skill set or a gut feeling like when you meet a family, how best to approach them. Usually, the first time we meet is pretty overwhelming, and you tell them a lot of things, and you really can't expect them to retain much of that. So I think repetition and just, you know, being patient with them, and we often have to go over things a few times for them to get it. And that's all okay. For me, the other thing that's important is just empowering them with knowledge, you know, tell them why we do things a certain way and why this medicine or why that, and I think once they hear the reason they're not just being told what to do, but they have to understand it. And that helps with them in learning and understanding. And just being honest. I think the patients, their families, they deserve to know everything that I know whether it's good or bad, and we talk about it and I share it with them.

00:19:36 

Host 

So what are the biggest challenges that you face as a physician and as a mom? How does that inform the way you deliver care and your own empathy in those journeys? And how do you cope?

00:19:47 

Dr. Zhao 

Being a mom 100% changed who I am as a physician, and as an oncologist because when I meet these families, I think that that could be my own children. So I feel their sense of loss, and I grieve with them. So I think it's important, which I talk about a lot with my team, is to walk this journey with them, because it's really the least we can do you know, their children are going through something that, just imagine that your own child's going through that. So, as a female physician with a little kid, I think we never have enough time. We're always struggling, like, you know, having to be at home and do the kids school stuff, and what's for dinner? And and, you know, balancing that with our commitment to our patients or at work. And I don't think I do it well, but I try. I think a lot of us just get by and and try our best.

00:20:43 

Host 

In terms of coping skills. I mean, obviously, it can be very emotional. So how do you cope with that?

00:20:50 

Dr. Zhao 

I don't think I've found the magic answer, or what really helps yet. I try to leave as much as I can here at work. But you know, there are some hard days and you can't just turn it off when you walk out of here. So it's something that even my partners who have a lot more years of experience, are still having a hard time. I think it just comes with what we do, and then something that we all need to learn, but I don't do it well.

00:21:20 

Host 

So talk a little bit about your neuro-oncology team, and also where the child's pediatrician or family physician fits into the team and the child's care, both in the initial diagnosis and the long term.

00:21:32 

Dr. Zhao 

I love my team here. That was a huge reason why I chose this program. I think they're phenomenal. It really takes a village to take care of these kids. And then your oncologist is just a small part of it. You know, I can't do it without the colleagues from neurosurgery, neuro radiology, my radiation oncology, pathologist, neuro psychology, palliative care, neurology, rehab, I think the list can go on because everybody on that team are important for the care of kids with brain tumors, you know, as well as my nursing staff, my research team down to all of our therapists, the dietictan, everybody. You know, they're all really important to me. And I don't think that missing any of these pieces will make the team function just as well. As far as pediatricians, we have developed really good relationships with them over time, and we try our best to communicate with them. They're usually the first physician or the first care team to realize that something's wrong, and they order the workups. And that leads to the diagnosis, which is super important that they are able to recognize what are the abnormal signs and symptoms of a potential brain tumor. Many of these pediatricians are family physicians checking on their kids during their cancer treatment, which we always welcome. And we love it. Because eventually, when they're done with their treatment, we do want them to go back to their primary care physicians and continue their care there.

00:23:13 

Host 

Sounds like it takes a huge village. And a lot that goes into the care of these kids. You mentioned earlier, your team follows patients through the Life After Cancer program. What is the significance?

00:23:27 

Dr. Zhao 

So we follow most of our patients for five years after they're diagnosed. Sometimes we follow them up to 10 years, if they have certain tumor types that we worry more about late recurrences, so we'll follow them extra long. But most of the patients once they are five years out of their treatment, or they're five years have stable disease. And you know, we send them to their survivorship clinic, which is a big milestone for them. The Life After Cancer program here is really designed to address the late effects that our patients experience after their treatment. I think it's super important. Because as these kids grow up, they may not remember exactly everything that's happened to them. So this program is designed to teach them what they have been through and why it's important for them to continue to receive ongoing medical care and surveillance. And so that's a part of our kind of transition, right? So we take care of them for a number of years, but their follow up doesn't end there. They continue to be followed in the Life After Cancer program, which is part of the program within hemonc.

00:24:37 

Host 

You mentioned late effects are they pretty common?

00:24:40 

Dr. Zhao 

Unfortunately, more common than most other types of pediatric cancers, because we're dealing with the brain, whether it's brain surgery, radiation, or sometimes even chemotherapy. Delayed effects that we see can be devastating. Um, we have kids that may have various degrees of learning difficulties. They may not be independent fully as an adult. Some kids have deficits in their strength, their balance, they may not be able to eat, see, hear well, they may have hormone issues. So all of these are complications as a result of their diagnosis in the first place, and then the treatment they receive.

00:25:28 

Host 

So when you diagnose a patient and talk about treatment with the family, do you talk about the late effects? Does that go into their decision making?

00:25:36 

Dr. Zhao 

We do, because we know how common that happens. And that is part of the conversation from the beginning. Because it's not a surprise, or this may not happen, it's more than likely your child will be experiencing these late effects. So we absolutely educate them early on. Now, sometimes we predict the worst and the kids do really, really well. And that's great. But it's always better to tell them what could potentially happen, than having them see their children not be the same.

00:26:12 

Host 

So cook children's is one of the largest freestanding pediatric health care systems in the nation. Even though it's not part of the university system it does have a close partnership with the TCU and UNT Health Science Center based in Fort Worth. How is the relationship with the medical school broadening the advancements in pediatric neurological medicine and research at Cook Children's today? And what do you foresee in the future?

00:26:36 

Dr. Zhao  

I think that's a really interesting question. And I know before I came to Cook Children's, this has always been a topic of discussion. I can see potential for future collaborations on research. This partnership between Cook Children's and the university system is also important for medical education. The Hematology Oncology program here, has always worked closely with medical student research projects. Earlier this year, I helped develop a curriculum for pediatric neuro-oncology elective, and we had our first medical student came and spent a month with us. It was a great experience, because now she's actually finishing up a publication as a result of her time spent here with us. So I think that relationship definitely needs to continue.

00:27:30 

Host 

That said, what are you working on?

00:27:33 

Dr. Zhao 

I'm working on a lot of things. There's always a lot on my plate that I can't cross off my list. But I do want to take this opportunity to bring a little bit more focus on our retinoblastoma program. So retinoblastoma falls within the Neuro-Oncology program, which is something that I also take care of. We have a multidisciplinary team here. And we are actively working on bringing intra arterial chemotherapy to our retinoblastoma patients here at Cook Children's. This is something that's only offered at a number of hospitals in the country. And we will be the first center in North Texas to offer this therapy to the patients. So I'm very excited. Stay tuned for updates.

00:28:20 

Host 

That is exciting news and super cool. Look forward to meeting again and talking about it. Yeah. I love that. Dr. Zhao, thank you so much for talking with us today. We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children's dot org

Listen Now

As more young people survive cancer, the issue of fertility preservation is front and center. Dr. Karen Albritton and her team explore the challenges of preserving fertility in children, teens and young adults undergoing cancer treatment and the latest breakthroughs in oncofertility that are delivering promise for the future.

Dr. Karen Albritton

Related Informtation

Oncofertility
Adolescent/Young Adult (AYA) Program
Life After Cancer
Oncology
Hematology and Oncology
Hematology and Oncology Research
Fort Worth Adolescent and Young Adult Onoclogy Coalition

Transcript

00:00:02

Host: Hello and welcome to Cook Children's Doc Talk. A while back we talked with Dr. Karen Albritton the medical director of Cook Children’s adolescent and young adult program in the Hematology and Oncology Center, and she oversees the Oncofertility Program. We also spoke with Olivia Prebus who was instrumental in developing the role of fertility navigator for the program. More recently, we talked with Toni Leavitt who we’ll be introducing later in the program. Toni is the current fertility navigator and we'll be sharing updates about the Oncofertility Program.

Dr. Albritton is trained in both pediatric and medical oncology and specializes in the care of adolescents and young adults with cancer. She recognizes the unique needs of these young patients and the challenging decisions they face about day to day living that most people take for granted. One of the biggest and often overlooked as how fertility is impacted by the cancer treatment they receive. As an active advocate for AYA cancer patients, doctor Albritton was instrumental in founding the AYA program here at Cook Children’s as well as the Fort Worth AYA Oncology Coalition, which provides resources for cancer patients and survivors, health professionals and community members. The Fort Worth AYA Oncology Coalition launched the first community supported AYA oncology inpatient unit in the nation and offers young adults diagnosed with cancer age relevant resources and specialized care designed to improve their lives before, during, and after cancer.

It is through her experience with AYAs that doctor Albritton has seen a need to consider fertility as part of all pediatric cancer care and establishing the oncofertility program here at Cook Children’s. Welcome.

00:01:48

Dr. Albritton: Thanks for having us.

00:01:51

Host: So let me start by asking what oncofertility is and why it's important?

00:01:55

Dr. Albritton:  Oncofertility is a relatively new term in the cancer world and it is a combination of 2 fields, reproductive endocrinology which deals with fertility for people with and without cancer for many different reasons who are seeking to either preserve their fertility or attempt to have children to use fertility methods to have biologic children, and many years ago it was realized that cancer patients have their fertility affected by the cancer treatments and that these 2 fields came together in a way to try to preserve fertility, monitor fertility. enhance fertility. All the crossovers of those 2 fields. And it became relevant that we were having conversations together and use each other's knowledge and science to have the best outcomes for our cancer patients.

It's important to mention that there are other disease processes, other conditions, in which fertility is affected and a lot of the things that we’ll be talking about today are offerings or conversations that we also will have the ability to have with patients in other departments. For example a patient undergoing a bone marrow transplant for sickle cell disease would have their fertility affected because of the transplant and they would be included in the offerings that we'll be talking about in our Oncofertiltiy Program.

00:03:15

Host: So tell us more about the Oncofertility Program here at Cook Children’s, your roles and how this program got started. 

00:03:22

Host: Just like I've said about the burgeoning of this field, I think the cancer world and especially the pediatric cancer world realized in the last 10 to 20 years that we had a good problem and that was that we had long-term survivors that wanted to have a very normal life. And that included having biologic children. And so we started having to answer up front even before cancer started the question of, will this affect my fertility, will I be able to have children, is there anything I need to be doing to enhance or protect my ability to have children? And so about 10 years ago we instigated a policy that all children after the age of puberty we would have a discussion right after diagnosis about how our proposed therapy would affect their fertility and whether there was anything that we could do to preserve their fertility. And that's a policy that we've had here at Cook Children’s.

We started using our AYA navigator, Olivia, as an additional resource to answer some of those questions. She's often the point person who is describing a lot of the programs and offerings and risks and education to the patient and the family. But there are a wealth of people throughout the hospital and throughout town who help make all that happen. Within the hospital the oncologist is the first person who will bring up to the patient and family that the treatments that we're proposing may impact their fertility and tell them that we'll have more information given to them by our Oncofertility Program. We then work often with surgeons and increasingly we are going to be using surgeons to do some of the procedures that will be involved in fertility preservation. Our urologists will also be involved in doing some of testicular procedures. We thankfully have great partnerships in town with our reproductive endocrinologists. Because we’re a children's hospital, we don't have on-staff reproductive endocrinologists but they're an important part of our program in the tissue preservation and also in some of the counseling for some of the elaborate procedures that may go on for future fertility.

In addition our support staff is important, the psychologists, the ethics committee here, our social workers are all involved because of the complexities of this program and the procedures that we're talking about. They can be expensive, they can be emotionally draining, there can be ethical issues involved, and so it really takes a whole team here at Cook Children's to make this Oncofertility Program work.

00:05:44

Host: So what additional disciplines make up the oncofertility team and what roles do they play?

00:05:44

Dr. Albritton: Because we're a children's hospital we don't have some of the reproductive endocrinologists right on staff that we would need to fully flesh out as some of the options that we would want and so we have partnered with some of the reproductive endocrinologists in town who have been wonderful at really working closely with us, being available nights and weekends and just bending over backwards to really make sure that our cancer patients have all of their options at their fingertips. Especially before they start cancer therapy but then after cancer treatment as well and they continue to follow them monitor their fertility help them with any IVF procedures etc.

Within the hospital we partner with our surgical team and our urology team if there any procedures that need to be done and we'll talk about some exciting ones that we have increased the partnership with because of some exciting opportunities.

00:06:44

Host: Olivia, are all pediatric cancer patients at risk of infertility due to treatment?

00:06:49

Olivia Prebus: Not all children with cancer are at an increased risk for future fertility problems. The risk to future fertility really hinges upon certain elements in a person's treatment plan. So what we're looking at is the type and dose of chemotherapy that the patient will receive, whether or not they'll have radiation, where that radiation will target, and what doses that radiation will be, and what if any surgical procedures might directly impact reproductive organs. So what we know is when we look at this treatment plan we can very quickly assess whether or not a particular patient is at risk. What we do know though is that just because a patient has not reached puberty does not mean that they do not suffer any long term impact of fertility if their treatment plan includes any elements that might impact it negatively in the future 

00:07:41

Host: So how is the level of risk determined?

00:07:45

Olivia Prebus: So the process to establish the risk to a patient’s fertility is a multiple step process. The first part really consists of sitting down with the oncologist who will be treating the child and really learning what the treatment plan is going to look like. So by that we mean what chemotherapy, radiation, or surgery might feed into treating this patient's cancer. Once we have a sense of the treatment plan we then go and pull out those high-risk elements that we talked about before. So the certain chemotherapies that we know have long term negative impact on fertility, we pull those medicines out and then we calculate the doses. Similarly, if we see that radiation may impact reproductive organs, we will then again calculate a dose. So once we know doses of high-risk medications or high-risk radiation we then will go to risk assessment tables. And these tables are really a way of bringing together the best available evidence that we currently have for assessing the risk to future fertility. And they are changing all the time as new information comes to light. And a large portion of what these tables are based on are population-based studies of long term survivors, so looking at patients who were treated for cancer and what are their long term outcomes around fertility.

So in order to make sure that we're keeping ourselves up to date with this best available evidence we really continue to make sure that we're in close contact with the different organizations around the country that are continuing to refine these risk tables.

00:09:12

Host:  And is there a difference in how males and females are affected? Is one gender at higher risk of fertility challenges than the other?

00:09:22

Olivia Prebus: That's a really difficult question to answer with a yes or no, but absolutely there are different factors at play when you're thinking about risk to fertility for a male or female patient. For male patients the damage really occurs to the cells that help the body produce sperm. That damage can occur even before puberty. So what we're really talking about in terms of risk is sort of a a range from an complete inability to produce sperm, to a completely normal sperm count after treatment or somewhere in the middle. so lower than normal sperm count. And so really what that looks like if you're talking about fertility or infertility is it is a spectrum that were counseling patients on.

With female patients, the damage is occurring to cells that are already present in the body. So female patients, the risk is a bit different because biologically they are born already with their full ovarian reserve. So the damage that is caused to oocytes, whether they're mature or immature, by chemotherapy or radiation, diminishes that ovarian reserve. So again, I guess it's fairly similar to men and that there is a spectrum but what we're talking about really with women tends to be if you're not going to be completely infertile due to your treatment we're talking about a reduced window of fertility, so you have fewer eggs, which means that the time at which she will menopause may be sooner than somebody who hasn't received treatment. 

00:10:48

Host: Dr. Albritton, what are the different preservation options for boys and girls. 

00:10:54

Dr. Albritton: Currently we have the option of sperm banking. That is only an option for boys who have mature sperm which happens at puberty. The sperm banking is done through masturbation and that is something that we have to assess whether the patient is psychologically and emotionally and physically mature enough to produce a specimen for. That specimen can be saved for an indefinite amount of time, there are children who have been born out of specimens that have been stored for 20 years, so any post pubertal male is offered the option of sperm banking.

For females the options are much more limited. The only approved option right now in the United States is to collect an egg and either to freeze the egg itself unfertilized or to fertilize it with a sperm and freeze that embryo. This is a complicated option for our patients for several reasons. Most of our patients in the pediatric hospital do not have a sperm donor either they’re and married or do not have a partner that they would want to fertilize and create an embryo with, but thankfully we do have the option now in the last few years of freezing oocytes. Those oocytes, like frozen sperm, can be stored an indefinite amount of time and then be fertilized later when the patient is ready to have a family.

There are problems with oocyte collection. It is a complicated process that involves hormonal stimulation that takes about 2 weeks of time and often we do not have that length of time available to us before we want to start aggressive chemotherapy. In those patients we do offer ovarian supression with hormonal therapy. It's somewhat controversial as to how much that protects the patient from infertility from their cancer treatment and that it is something that both will at least keep them from having menstrual cycles and anemia during their cancer treatment and it may actually protect their ovaries somewhat long term from some of the damages of chemotherapy.

That has been a rather unsatisfactory menu of options for cancer patients and for a long time we've been hoping to have more options for a couple reasons. One is because all of those options I just mentioned are all for post pubertal patients. The other is the issue of time for the females. We are excited now to have several options on the horizon that will overcome some of those problems. For females we are excited to start offering ovarian tissue cryopreservation. This is a procedure in which an ovary is removed at the time of another surgical procedure before chemotherapy starts. That tissue is sectioned and parts of it are frozen just like we talked about freezing sperm or oocytes. It is stored away for future use.

The technology is rapidly advancing and there is incredible work being done as to how those samples then will be used and reimplanted in the body. This is different than how we talked about using oocytes and sperm in terms of using in vitro fertilization outside of the body and creating an embryo that then is implanted in the uterus. This is actually reimplanting the tissue that we have surgically resected into the now cancer survivor, and having it revascularized, start to become healthy again, and start making healthy eggs again within the body. What is unclear yet is whether those then are harvested and again in vitro fertilization is done. There are exciting opportunities potentially to reimplant the tissue even in the pelvic and have normal pregnancies. In any case, now that we know that it is safe and efficacious to do ovarian tissue cryopreservation, we feel it's an important offering for our young children even if we don't know how exactly it's going to be used in the future. This would be an offering available to patients of any age so now our prepubertal females will also have an option to preserve their fertility.

In males we also are looking forward to the opportunity to offer our prepubertal males testicular tissue cryopreservation. This is still experimental and we will be participating in a multisite clinical trial looking at the safety and efficacy of this. But it is something that we would offer families whose sons are at very high risk of infertility, as an opportunity to possibly preserve their fertility and certainly contribute to the field of research of oncofertility.

00:15:28

Host: So that said, Olivia, what are the challenges for kids and parents in making the decisions?

00:15:34

Olivia Prebus: There can be many challenges. We like to think of offering fertility preservation as offering a ray of hope in a really dark time in a patient and family's life. And I think that many patients look back on the conversations with that but in the moment it can be a lot of information to process on the heels of just being told that their child has cancer. And so there's a whole lot of emotional processing and then we're layering quite complicated information on top of that. So I think that is one of the biggest challenges that we see. The second, and probably it goes hand in hand but the first, is the timing. So in pediatric oncology the time from diagnosis to the start of aggressive treatment is very short for the most part. So when we're talking about decisions that need to be made and executed before starting chemotherapy or treatment there is a lot of pressure to make a big decision like this, so we try our best to get in there and start the conversation in order to leave as much time as possible for the family to sit with the information, ask those clarifying questions, and make the decision that's right for them.

Another thing that we encounter that's a challenge for more for the patient perspective is developmentally young teens have a very difficult time projecting into the future, So they often are very hard wired to think only about what is right in front of their face. And so when you're talking to a 14, 15 year old boy about masturbating, they can often get very caught up in, that's extremely embarrassing, this is a private thing that I'm not used to having anybody else know about and now you're talking about this and my parents know what's going on.  And sometimes I can be a real barrier for these patients to get past. And not all patients do. For some patients that's the reason they decide they don't want to pursue sperm banking.

Um, similarly for female patients, we’re talking about surgical intervention and shots for 2 weeks straight every day, I mean, these are not easy things to ask of of young people and so sometimes that can be another challenge. Often times parents can be very helpful at reframing the conversation but were always very mindful of discussing there is no wrong option. And really and truly very rarely is there tension between the decision the patient makes some of the parents want but sometimes that does happen, but we're really trying to create a nurturing environment so that this patient feels like they have some choice to make at a time when they don't feel they have a lot of options or choices.

Another challenge that's very real in the current environment is financial. Oocyte cryopreservation is extremely expensive. There are programs that can help defray the costs of the hormonal stimulation medications but when you're talking about a surgical procedure under anesthesia you know 4 to 10 thousand dollars up front is an awful lot of money when you've just found out that your child has cancer and you're anticipating additional health care costs to your family. Then we have to think about long-term storage costs, especially for younger patients. If you're talking about an annual storage fee of 4 or 5 hundred dollars a year, adding up over many years until a child is ready to start a family, that can also add up. Sperm banking, while not as expensive on the front end because that does not involve surgical procedures, is also costly when you think about long-term storage. So as best we can, we try to identify ways to defray the cost so that that doesn't become the reason, or the sole reason, that somebody chooses not to pursue if they would otherwise wish to do so.

So given these really difficult choices and really difficult um things that we're asking patients to do, um we always also like to make sure that we are saying there is no wrong answer and if you decide today and now that sperm banking or oocyte banking is not the best decision for you, we always talk about other methods of building a family in the future in the event that their current treatment does render them infertile. Really, our biggest role is to provide information and in no way would we ever want to feel like we're pressuring a family or a patient to make any decision. We really do just provide the information and some context so that they can make the best decision for them.

00:19:52

Host: So from what I've read, there are also ethical concerns with regard to oncofertility. What are those and how can they be overcome?

00:20:00

Olivia Prebus: This is a really rich area of study within the oncofertility community, and I really commend the discipline for really taking this ethical approach from the very beginning. There are many ethicists who write articles and books about the ethics of oncofertility. So with that as a backdrop, we’re really just focusing on 2 or 3 of sort of the top issues that seem to come to mind. The first really does play into some families decision making. There is a very real use of IVF and other assisted reproductive techniques involved in the future use of stored reproductive tissue, stored sperm, all of this. And so for some people it is ethically a difficult area when you're talking about embryos and IVF and things like that. The way that we mitigate this is, as we've talked about before our job is really to lay all the information on the table. Our job is not to pressure anybody into making a choice that does not sync with their values.

Another question has to do with for those patients that elect to pursue fertility preservation, if that patient then dies what happens to the tissue? So this is an area that's particularly difficult for minor patients. A patient over the age of 18 can very clearly and legally write out their intention as to what happens to their reproductive tissue in the event of their death. For a minor patient there have been some cases of parents wishing to use the reproductive tissue of a deceased child in order to have grandchildren. The way that this is circumvented here, and increasingly at many practices around the country, is to put very plain clear language in all consents and all conversations about the use of tissue in the event of the patient's death. We really feel that that tissue is part of the patient and the purpose of fertility preservation is to preserve the patient's ability to be a parent. And if the patient is no longer living they can no longer be a parent so we really very clearly state that in the event of a child's death or patients death at any point before they turn 18 that issue needs to be destroyed and not be available for use by other individuals.

A final, and very overarching, ethical question that really informs the presence of oncofertility as a discipline has to do with the real informed consent of patients and really understanding the impacts that their treatment will have. All of the major oncological and reproductive medicine societies have come together and said you know it is extremely important that patients are fully and transparently educated about the risks that their treatment, which is lifesaving, may have on their future fertility, and to withhold that information is ethically inappropriate. So even just the act of having the conversation and presenting the options really does overcome what is a very serious ethical obstacle that is, quite frankly, still a problem within oncology at large. This continues to be a problem despite all of these recommendations from professional societies.

00:23:11

Host: Dr. Albritton, as cancer treatment improves so does survivorship. How does that drive the need for fertility preservation?

00:23:20

Dr. Albritton: As I said before it's a good problem to have that we have so many children surviving their cancer treatment and hoping to be parents themselves. Many survivors when interviewed about the impact of cancer on their lives, cite fertility or infertility as a major grief in their life. Many of them say finding out they were infertile was almost worse than the cancer itself. Many of them are very bitter that they were never told about the risks to their fertility before their treatment. This is one of the reasons we feel so strongly that patients and families should be educated before treatment, they need to know the risks going into treatment and what we can potentially do about it. So it's a good problem to have that we have so many survivors, that the survivorship community is calling for us to at least educate them and hopefully to mitigate the risks. One of the things that the survivorship community has started to advocate around is not only education but the payment of fertility preservation options by insurance companies. Currently, insurance companies do not pay for fertility preservation options standardly, and as Olivia mentioned these can be very very expensive procedures. And it is heartbreaking when a family actually decides not to pursue an option solely because of a financial reason because their insurance company wouldn't cover their fertility preservation. Thankfully, at Cook Children’s we have some philanthropic donors who help mitigate that but the advocacy community at large is really rallying around the idea that this should be a right of cancer patients to have their fertility preserved prior to starting treatment.

There's now legislation in several states and it is pending in Texas it is being considered whether we can redefine the definition of infertility in a way that includes iatrogenic, meaning caused by physicians caused by medical care, and that would then allow coverage of these procedures prior to the start of cancer treatment. That would be a wonderful, wonderful change created by the cancer survivor advocacy community as a way to expand the options for cancer survivors to have as normal a life as possible.

00:25:35

Host: So Olivia, let's talk about fertility post treatment. Is there a longer term need for fertility discussions among survivors, meaning how long after treatment might a person be affected by a decline in fertility?

00:25:48

Olivia Prebus: The fertility discussion only begins at diagnosis, it really is something that threads through the rest of the patients oncology care into their survivorship care and really impacts them for the rest of their life. We have made it a priority to include conversations about reproductive health and fertility throughout this treatment continuum, into survivorship. So I will meet the family at the beginning of their treatment to discuss the risks. Sometimes treatment plans will change, depending on how well or poorly a patient responds to treatment. So if there are ever changes in their risk assessment we also go back and have that conversation. Looking into survivorship care, we like to make sure that we again revisit the education that was provided in context of their treatment plan because we know that patients may not remember or remember very clearly the conversations that they had with you when they were in great distress at time of diagnosis or during treatment. So this can sometimes be a great opportunity to clarify not just risk but what then this means for them and their survivorship care.

When you're talking about male patients, to answer your question about how long is the impact, studies show a wide variability as to when sperm counts normalize, if they will normalize, anywhere ranging from 2 to 10 years. So it's very important to counsel patients on a number of things. One is to make sure that they're engaging in safe sex practices if they are sexually active, not assuming that they're infertile. The other is helping them to understand what options exist for them to reassess what their sperm count is, and their sperm health, and when they might do it. Being that there are costs associated with semen analysis, our general guideline is for patients, if they're dying to know and they want to know, wait 3 or 4 years and if you feel like you'd like to have a semen analysis absolutely we can refer for that. Otherwise, we often say when the patient is ready to start a family that might be a good time to get a semen analysis before sort of starting that process with their partner.

For female patients the conversation is a bit different. So we're talking about potentially a smaller window for reproductive ability, or a smaller window to start a family. Many patients will still have ovarian reserve at the end of treatment so they will still have the ability to have children. But they may, as we said earlier, have an early menopause. And with women, as the ovarian reserve decreases there are other more systemic health issues that they need to be mindful of such as cardiac health, bone health. So really it is a much more global wellness picture that we're talking about even as we're talking about fertility. Female patients who maybe did not have the opportunity or chose not to egg bank prior to treatment may have that opportunity in this window after treatment.

So a large part of the survivorship care is monitoring lab work and then making appropriate referrals to reproductive endocrinology clinics for those patients that we identified as being at a higher risk in survivorship.

00:29:05

Host: So who follows up with these patients after treatment is complete? Is it the oncology team, primary care physician?

00:29:14

Olivia Prebus: Primarily it is the oncology team that does the closest monitoring of patients and their survivorship care. So the first 2 years after a patient completes active therapy, we call this the surveillance period where they're still coming very regularly to their primary oncologist for care. And really, during this period it's about starting to monitor for long term effects but it's also about being very vigilant about the possibility of a relapse. At Cook Children’s, we then transfer our patients to our Life After Cancer program for more long term survivorship care. The ultimate goal is that at some point the patient will then return to a more primary care model, but then continue to have a very clearly defined plan to monitor for long term side effects of their care.

00:29:59

Host: Dr. Albritton, is there a lack of training or knowledge among physicians when it comes to pediatric oncofertility?

00:30:07

Dr. Albritton: Absolutely. And for good reason. This is a rapidly, rapidly changing field. There is a lack of knowledge even among the experts in the field. Ironically, this morning there was a flurry of emails in my inbox among a group of highly trained specialists in oncofertility having an exchange of ideas about the best way to offer contraception to cancer patients. So if this group of specialists still can't answer all the questions there is absolutely a lack of knowledge in both oncologists and certainly in primary care providers.

So much has evolved in our understanding of what groups of patients are at risk after what amount of treatments, that the average oncologist really needs to be able to turn to a group that is keeping up with that information and has the latest information and is giving the appropriate risk information to the patient. In the past, we've had so few options to offer in oncofertiltiy that I think it was sadly common for treating physicians to skirt the topic. It is very hard to know that you will name a problem and not have a solution for it. So to tell a patient and a family, the treatment I have just described will make you infertile and I can't do anything about it. is heartbreaking. And I think that many physicians try maybe to even avoid having any discussion to avoid that second grief at the start. Or they wouldn't know they didn't know what the risk was. As we gain information and we're able to more clearly define risks, and wonderfully have increasing options to offer, it's our duty to access the information from the specialists and pass that information on to our patients at Cook Children’s. The important thing for primary care doctors to know is that there’s hope. And to tell their patients and families to make sure that they ask about the risks of infertility based on their cancer treatment and ask if there are any options available including experimental options because there may be clinical trials available to them to preserve fertility.

00:32:18

Host: Are there steps that the medical profession can take then to assure that more primary care physicians receive training in the importance of oncofertility?

00:32:26

Dr. Albritton: As I said, I think the field is so specialized, I'm not sure there will ever be widespread knowledge to the primary care physicians about all these details of treatment options. What I really want them to know is that we are a resource. At Cook Children’s, we will always be keeping up with the latest available options, the state-of-the-art clinical trials that we can offer our patients to make sure that they are getting the best options offered to them. We are always available as a resource. We know that as a team we are not only helping the patient and the family navigate cancer, but we consider the primary care physician part of our team and want them to have all of their questions answered and we will always be a resource and they're welcome to call us.

00:33:08

Host: Now I'd like to introduce Toni Levitt who, as mentioned earlier, has taken over the role of fertility navigator. Toni a lot of really exciting things have happened since the Oncofertility Program was first launched, can I just say welcome, and before we dive into that can you tell us just a little bit about you and when you joined the program?

00:33:30

Toni Leavitt: Hi and thank you for having me. I'm actually a nurse practitioner by training and I'm dually certified in both adult oncology in family practice. I've been in the nursing field for about 10 years and became an oncology nurse because I just love taking care of patients and oncology patients specifically because it's a particularly vulnerable time for them and their families and I love having the ability to support them. When this position came up to manage both the Adolescent Young Adult, or AYA, and oncofertility programs here at Cook Children’s, it seemed like a really perfect fit, based on my interests. I really enjoy the direct patient care and program managereal responsibilities such as data collection and project strategy.

00:34:12

Host: And how long have you been with the program now?

00:34:15

Toni Leavitt: I joined Cook Children’s at the height of the pandemic in July of 2020 and it's been a really exciting few months.

00:34:23

Host: I bet. And what are some of the latest updates in oncofertility here at Cook Children’s since you've come on board?

00:34:29

Toni Leavitt: It's been an exciting time since I joined. As mentioned, Olivia and Dr. Albritton had worked hard exploring how to bring prepubertal fertility preservation options to Cook Children’s, including both ovarian and testicular tissue cryopreservation. Since arriving at Cook Children’s we've actually expanded our offerings. First, we now have a research study for testicular tissue cryopreservation, which is an opportunity for post pubertal males to preserve a portion of the testis to use for future fertility. This is only an option for our male patients who are at very high risk for infertility. For our female patients who are prepubertal, we now offer ovarian tissue cryopreservation. Like testicular, we only offer it when that individual is at very high risk for infertility due to their treatment, which can be surgical, radiation, or chemotherapy related. Ovarian tissue cryopreservation is when an ovary is removed and cryopreserved for future fertility. This is no longer considered experimental.

Shortly after I arrived, we identified a prepubertal female patient who would benefit from ovarian tissue cryopreservation. We offered this to the family and they seemed interested, mainly because the dad didn't want to eliminate future fertility for his daughter. On the day of the surgery I had the opportunity to go into the operating room with doctor Blake Palmer, and received this tiny ovary, sent it to Pittsburgh, where it will be preserved for future use. It was a really rewarding experience for the family, of course the patient, and all of the medical team members involved.

00:36:19

Host: So in terms of advancements in fertility preservation, some of the biggest changes are in ovarian and testicular tissue cryopreservation, also known as OTC and TTC. Can you share a little about this?

00:36:31

Toni Leavitt: OTC is a clinical offering, so it's no longer considered experimental here or anywhere else, while TTC, or testicular cryopreservation, is under an IRB or research protocol that is part of a national study. Eligibility will be carefully considered by the medical team prior to offering and while these cases will be few and far between as it's only offered to those at very high risk for infertility, I'm thrilled that we now have these options available here at Cook Children’s.

00:37:03

Host: What about other forms of fertility preservation? What alternatives are available and at what age can they be considered for an oncology patient. 

00:37:12

Toni Leavitt: For post pubertal males, it's our policy to offer sperm banking, and for our post pubertal females we can coordinate oocyte or egg cryopreservation or embryo cryopreservation for those who have a partner. We work closely with the reproductive endocrinologists in town to offer these options. For our prepubertal patients, those who have not yet gone through puberty, OTC and TTC are the only possibilities, and still it is only offered to those at significantly high risk for infertility due to the treatment they'll be receiving. We continue to hope that fertility preservation laws will be passed to make all of these options affordable for our patients and work closely with an advocacy group to support that initiative here in Texas.

00:37:56

Host: You mentioned prepubertal children who have serious types of cancer, what are the challenges? Like why do they have to be at high, high risk? And is there an age cut off for that?

00:38:07

Toni Leavitt: We define significantly high risk for infertility as those receiving a very high dose of chemotherapy, where it is unlikely that they will be fertile in the future. Or they are receiving radiation to either at the brain or the pelvis that will also affect their fertility. Ovarian tissue cryopreservation and testicular tissue cryopreservation involves removing that tissue from the patient and so our preference is to not remove that tissue unless absolutely necessary to preserve fertility.

00:38:42

Host: So when you say remove the tissue then is it like perhaps the whole ovary or testicle?

00:38:49

Toni Leavitt: Yes

00:38:52

Host: It's gotta be really, I'm sure in some cases, like a challenging choice for parents and for the patients. But it also has to be, I guess, somewhat reassuring that in the long term they can still go on and have a family and live as close to a normal life as possible, whatever a normal life might be.

00:39:12

Toni Leavitt: Absolutely. I remember talking to the parent of our first patient and he said, I don't want to make the decision for her, I want to keep this option open for her. 

00:39:25

Host: As cancer treatments improve, and childhood cancer survivors go on to live fulfilling lives as adults, the ability to help ensure that even young patients can look forward to having children some day is absolutely amazing. And as more advancements in medical breakthroughs come in both cancer and fertility care, what does the future look like. 

00:39:46

Toni Leavitt: It would be fantastic if we had less toxic treatments that did not impact fertility as significantly as the ones we currently rely on do. I hope that the future entails coverage for fertility preservation for all of our patients, making these options a possibility for everyone who would benefit from them. I would also love to consult not only with those who would benefit from a method of fertility preservation but also those at low risk for infertility to provide reassurance to them. One benefit of COVID has been the increased use of telemedicine and with time it would be great to provide fertility counseling via telemedicine, so we can expand our reach beyond the medical center. Many goals, but I think all of these would be incredibly fulfilling for our patients.

00:41:24

Host: That was really, really informative. Thank you for taking the time from your hectic schedules to talk about fertility preservation and about the important work you're doing for pediatric oncology patients at Cook Children’s as well as across North Texas and the U. S.

00:40:50

Dr. Albritton: Thank you so much and for talking about this important topic.

00:41:04

Host: We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children’s please visit us at Cook Children’s.org.

Listen Now

Dr. Clarissa Johnson peels back the curtain on the unique challenges for pediatric patients with sickle cell disease, the risks involved with transitioning to adult care, and clinical trials and research that offer hope for a brighter future here and around the world.

Meet the speaker
Dr. Clarissa Johnson

Related Information
Sickle Cell Disease
Hematology
Hematology and Oncology
Clinical Research

Transcript
00:00:04

Host:  Hello and welcome to Cook Children’s Doc Talk. We're here today talking with Dr. Clarissa Johnson about sickle cell disease and the advanced treatments and research she leads here at Cook Children’s. Dr. Johnson is a member of Cook Children’s hematology and oncology team and the lead physician of the Sickle Cell program. She is actively involved in research Cook Children’s and has written extensively on the unique medical care needs an infection risks of children with sickle cell disease. In addition to her work at Cook Children’s Dr. Johnson has also made many medical mission trips to hospitals and clinics in Nigeria, Ethiopia and Eritrea. Those trips help to provide her with an even more intense drive to find a cure and she puts that drive into action every day in the compassionate care she provides to patients and families at Cook Children’s. Dr. Johnson, welcome and thank you for being here today.

00:00:55

Dr. Johnson: Thank you for having me.

00:00:58

Host: Can you start off by telling us a little about Cook Children's Sickle Cell Program?

00:01:02

Dr. Johnson: The program at Cook Children’s was established many years ago when the hematology oncology division was started at this institution by Dr. Paul Bowman. It has evolved over the years and by the time that I started working here in 2009 it was a well established program. I became the program director a short time after that and since that time have worked really to bring more research trials to our patient population and to have a cohesive management of care. Our team includes a nurse, a therapist. a social worker, and then three physicians who primarily take care of the patients here, of which I am one. We follow about four hundred patients from across the state of Texas, so that includes patients in West Texas, north of us in the Wichita Falls area, now Tyler in East Texas, south of us in Waco and then of course here in the immediate DFW area, which is probably where most of our patients come from.

00:02:01

Host: Can you tell us maybe a little bit about the types of advanced research trials we’re part of.

00:02:06

Dr. Johnson: Over the years Cook Children’s has been invited to participate in several trials, including trials on iron chelation in children, that is something that we use in children with sickle cell who need transfusion therapy and overtime may have iron levels build up in your body because of that, so we participate in that trial. We have collaborated with the group over in Dallas with some trials to look at the effect of something called a patent foramen ovale, or a small hole in the heart in terms of its influence on the risk of stroke in children with sickle cell disease. And in recent years we've been part of some therapeutic trials for various pharmacologic agents that have been developed trying to determine if there are medicines that will help us reduce the incidence of the most commonly seen complication in patients which is pain. So we have more recently done a trial looking at a drug that can be used in patient when patients are hospitalized to reduce the duration of their pain episodes and we are currently doing another trial of that nature.

And upcoming hopefully will be two other trials which are both outpatient, one looking at an oral medication that can be taken every day to try to increase the hemoglobin in patients with sickle cell disease, and that’s something called voxelotor, or GBT440. And another drug this called crizanlizumab which is also an outpatient drug which may also help reduce the frequency of pain crises that patients have when that drug is given once a month. So that's a trial that's not open here yet but we're looking forward to hopefully being able to participate in that when it is.

00:03:34

Host: According to the National Human Genome Research Institute, sickle cell disease is the most common inherited blood disorder in the U. S. particularly among African and Hispanic Americans. In fact, according to them, one in twelve African Americans and approximately one in one hundred Hispanic Americans carry the sickle cell trait. With so much prevalence why is it so challenging to find a cure?

00:03:58

Dr. Johnson: So. there is a cure for sickle cell disease which is stem cell transplantation. The limitation with that cure is that is not universally available to all patients. So we say is that we don't have a universal cure at this point. The other issue with stem cell transplant is that it requires you to have a donor. For most people a matched sibling is going to be the best donor but that presents challenges if both parents are carriers of a trait that causes the sickle cell disease, and therefore at risk every time they have a child to have another child with sickle cell disease. So that makes it challenging to encourage the parents to have more children with the idea of having a donor because for one there's only twenty five percent chance that that child will be a match for the affected child and they are also putting themselves at your twenty five percent risk to have another child with he disease. So that makes it a bit more challenging. Even parents who do have other children who are not affected that child needs to be a full sibling, so that's one limitation and again there is only a twenty five percent chance that even a full sibling is going to be a match. So that makes it difficult. We sometimes will do unrelated donor transplants because we can find people who can be a match for us even if they are not directly related to us but there are some more risk associated with doing that type of transplant as compared to a matched sibling transplant. So we typically reserve unrelated donor transplants for patients who are having the most severe complications in terms of determining what risk of transplant is acceptable to find a cure. So there are many limitations right now to what we have available to offer in terms of a cure for patients.

00:05:37

Host: It wasn't that long ago that babies born with sickle cell disease rarely lived past childhood, but thanks to continual advancements in treatments people with sickle cell disease are living well into their fifties. So can you talk a little about how treatment for sickle cell disease has changed over the past few years.

00:05:54

Dr. Johnson: There have been a lot of advancements in the treatment for sickle cell that has allow patients to live longer. Many many years ago patients were dying from infection when they were children and so one of the first real advancements was realizing that these children were having infections more frequently than other children their age and that by putting them on an antibiotic every day in early childhood that could reduce the risk for infection and therefore help them to live longer. Then, following that, vaccinations were developed that could also help prevent some of the infections that we worry about in sickle cell disease. The primary infection we worry about in young children with sickle cell disease is pneumococcal sepsis. And so that the bacteria called streptococcus pneumonia, which in the past it was probably the number one infection that was taking the lives of children with sickle cell disease. But with the development of penicillin, prophylaxis, and with vaccine prophylaxis, that has changed. So a lot fewer children are dying from that infection today. Children still develop that infection but I think with better treatment and knowing that they need to be evaluated quickly for fevers that has allowed us to reach them before that infection results in death.

So that was a major development. Other developments for children with sickle cell disease that has helped them to live longer include hydroxyurea. So that treatment was around for a while already treating cancers like leukemia but then it was noted that hydroxyurea tends to increase fetal hemoglobin and infants with sickle cell disease actually under the age of six months have fewer complications specifically related to the disease itself, and it was recognized that that was because their fetal hemoglobin levels are still very high, and the amount of sickle hemoglobin or sickle percentage in their blood was still low. That changes when they turn around the age of six months and then the fetal hemoglobin declines, so people start to look at what are ways we can try to maintain this high degree of fetal hemoglobin and can that protect kids from sickle cell disease from having complications. And they found that it could end so fart the best agent in terms of site of profile and response has been hydroxyurea. So there was a landmark trial in 1995 that look at use of hydroxyurea in adults with sickle cell disease and the study was actually terminated early because they found that people who were taking hydroxyurea as opposed to those who were not were having fewer hospitalizations, fewer transfusions, and less pain episodes. So that is a treatment that we now really propose for many of our patients especially those who have more severe disease or any of our patients who are looking for ways to try to reduce their frequency of pain episodes and hospitalizations

Unfortunately, that treatment is not something that works for everyone, so some of our patients who have types of sickle cells such as the sickle C disease and something called sickle beta plus thalassemia may not tolerate that medication as well. So that is something to point out is that there are different types of sickle cell disease and they are not all exactly the same even though there are many features that can be very similar and so hydroxyurea so far has mainly been a treatment for those with more severe disease and so that leaves us with a limited option for those who may have less frequent complications but still have complications and cannot tolerate that medication.

So we're still looking and there's lots of interest now from pharmaceutical companies in sickle cell disease and so that's why we have these research trials that seem to constantly be popping up in the last couple of years to the point they were now having to decide which ones we can do and, so it's an exciting time in terms of research I think for sickle cell disease, but at the moment we still really just have the one drug that is truly effective.

I will mention l-glutamine or endari because a lot of families may have heard of that or people who are reading on the Internet about sickle cell disease, that is a recently FDA approved treatment for sickle cell disease aiming to reduce pain episodes but the only caveat I would say, is that the effects were not as dramatic as hydroxyurea so some families have been interested in trying that medication and we've been willing to do that but the trials were not as dramatic as the hydroxyurea trials and so I think many of us are still looking for other options you know in addition to hydroxyurea that can help our patients live lives that are less interrupted by complications of the disease.

00:10:17

Host: So, there are a lot of advanced treatments and research currently available what are the most promising treatments and clinical trials.

00:10:25

Dr. Johnson: So at the moment the ones that stand out the most to me would be the GBT-440 or voxelotor, which is a trial that we hope to open here soon. That drug is aimed at helping the red blood cell to hold oxygen better and that's a red blood cell that contains sickle hemoglobin. And in that way allowing that blood cell to have a longer survival than a cell with sickle hemoglobin been would ordinarily have, and also helping that red blood cell to carry oxygen better too and deliver it to the tissues of our body. So if that drug is effective then it can help patients to have less severe anemia and potentially less frequent pain episodes. That drug, so far, is being used either with hydroxyurea or without in the trials that are being done for it.

00:11:13

Host: And how severe, because you’ve mentioned pain episodes quite a bit, how severe can that pain be.

00:11:20

Dr. Johnson: So patients will describe a different ways. Some people will say it feels like someone is stabbing them with a knife, others will say it feels like there bone is being broken. Right now the mainstay of treatment that we have for addressing that acute pain and when a patient comes in with pain is opioid medication like a morphine or dilaudid. And so that may make some people feel a little bit hesitant or afraid when they hear that you're using that kind of medication for their child but unfortunately that’s how severe the pain can be. So we're hoping that with some of these treatments many will have less of a need for opioids.

I’m not sure yet that we have treatment that will completely eliminate the need to use them but maybe we won't need to use them as much. And I think a lot of families would hope for that too. They use the medications because that's what's available and they're really at this point is nothing else that's going to make their child's pain significantly better and we don't want kids to suffer, we don't want adults to suffer, so right now we use what we have to use. But I think it would be ideal to have other treatments that actually address what's happening from the disease itself in the body that would help with that pain more so than a pain medication. Because pain medications, really, I think of as just being a bandaid. They can't really reverse the underlying process. And sometimes we need a really strong bandaid, sometimes we may only need some ibuprofen, it all just depends. And everybody's pain experience is different so you know we have to remember that as well.

00:12:48

Host:: So currently the only known cure for sickle cell disease is transplantation which we talked about. But is a genetic cure on the horizon, and what is your involvement in that research here at Cook Children’s?

00:13:00

Dr. Johnson: So, there has been more interest since the human genome project several years ago at gene therapy for a lot of different diseases, and because we have known the genetic mutation that causes sickle cell for a long time, it is one of the diseases that has been proposed as a candidate for gene therapy. There have been trials already in a small number of patients and there are patients who have received gene therapy and who have effectively been cured from the disease.

So there are two methods. There is one of essentially trying to fix the gene of a sort, and there's one of basically inserting a correction next to the gene that helps the sickle gene to behave better. So those are very promising studies. Some patients as I said have already received that treatment and so far the outcomes have been good, we move with a little bit of trepidation when we start talking about manipulating genes because we always worry about the risk for inducing a cancer like leukemia and so that's why sometimes studies of that nature can move a little bit slowly but we have been approached by one of the companies that is involved in that type of therapy and as they move forward with trials we hope to be able to participate in that, and have told parents you know it's not something we're doing right now in these sorts of things move a little bit slowly just because of the nature of what's being done but hopefully that is something that will give hope to have a universal cure in the future because for that type of cure, it doesn't really matter what type of sickle cell disease you have, it is something that would be more readily available to more patients and it also doesn't require you to have a donor because in this instance you would be using your own cells, having them corrected by whatever gene editing or corrective process is being done and then having those cells given back into the body. So we're excited about that potential option in the future.

00:15:02

Host: Until we find a cure what are the greatest risk to kids with sickle cell disease and how can those risks be reduced or prevented.

00:15:10

Dr. Johnson: At the moment I think one of the greatest challenges is the transition, because we often see that as our patients transition from pediatric to adult care there can be a drop off in care for them. In many areas around the United States in particular, there are not adult sickle cell specialists available and so that role of care for those adult patients with sickle cell may fall on either a primary care doctor or maybe oncologists, which in some cases may be sufficient, but in other cases may not be, because the level of expertise may not be there to address some real challenges that can develop on people or adults with this disease. And so we see an increase in mortality in our patients in their early twenties between the ages of twenty and thirty, and we think that is closely linked to the problem of transition and having an adequate number of people with expertise to care for adults with sickle cell disease. It is one of the reasons that many years ago the age of transition changed here at Cook Children’s to the age of twenty one because we did not want to leave our patients in a vulnerable position of transitioning not only from high school to some type of career or college or training program, but in maybe also transitioning from the family home to being on their own, and then to add to that a transition of medical care and potentially having a drop off in care. We feel that that was a real risk for our patients that could potentially result in mortality so that remains a very big challenge I think, and one of the biggest challenges that we face. I think we feel that we can manage most complications that may arise in our pediatric patients but we don't want to then help them have a full life through the age of twenty one and then have that drop off and that high risk for mortality. So around the country I think there have been efforts to try to figure out a different model for adults with sickle cell and how they can receive their care, and just encouraging more people who are doing the training of hematology oncology to consider being a sickle cell expert. We do have some luxury of having availability in Dallas for an adult sickle cell program and so that is where we refer most of our patients when they turn the age of twenty one, unless you're moving away from this area, but that still presents challenges, especially if you know based on geographics and where people live, it's still not the easiest and it may not, for some people, be the most ideal option.

00:17:40

Host: So one final question. Why is it so important to find a cure for sickle cell disease and why, beyond saving the lives of patients, does it matter.

00:17:50

Dr. Johnson: Well I don't know if people realize that sickle cell disease is really a global disease. So we only think of what we see in the United States. And the United States compared to the overall population is a small fraction of people maybe a hundred thousand people or so. But this is really a global disease that is all over the world. It affects people's ability to have a meaningful life and contribution to society if they are greatly affected by the disease and limited in their ability to reach their goals. We certainly see a lot of our patients, you know, strive to overcome that and certainly do very well with that, but it's a chronic illness. It’s a lifelong illness and it can also shorten the lifespan so I think when we ever we have a condition that causes so much medical burden for families and risks to not be able to live out your full potential because of a disease cutting that short, we always want to do whatever we can to help with that.

So I think it's very important to have more of a focus on this disease and I've been very pleased to see pharmaceutical companies and researchers starting to have more of a focus on this disease. And I think it's also very important for our families to get involved as well and trying to push that focus in trying to push legislatures and people who have the ability to improve funding for research to do so.

00:19:08

Host: If a family or someone in the medical industry listening to this wanted to get involved in making those changes, or giving a voice, how would they go about doing that?

00:19:18

Dr. Johnson: One good place to start would be the state legislature. Recently there are some committees that have been developed for looking at sickle cell disease and how it impacts the families and health care systems in Texas. So I think that's really one of the main places where change can be enacted. It's a little bit difficult for that to come strictly from a medical center because it's more of, at least referring to Texas, is more of a statewide issue. And so I think the more families sort of raise their voices and let legislators know that they have family members or friends who are affected by this disease and that they want to see more being offered for their family members and improvement in the cure really around the state, I think that's really a number one way to have change enacted. And I think we've seen that model with other diseases with some success.

00:20:08

Host: Dr. Johnson thank you for being here today and for sharing your extensive knowledge on the strides being made in the treatment of sickle cell disease for kids right here in Fort Worth as well as around the globe. And thank you for all you do here at Cook Children’s.

00:20:21

Dr. Johnson: Thank you for having me

00:20:23

Host: We're so glad you could join us today. If you'd like to learn more about this program or any program at children's please visit us at Cook Children’s dot org.

Listen Now

Dr. Paul Thornton and Dr. Blake Palmer lead a lively round-table discussion on reaching clinical excellence through exceptional interdisciplinary care for patients and families.

Dr. Paul Thornton
Dr. Blake Palmer
Cortney Wolfe-Christensen PhD
Emily Haddad LCSW

Related Information
Congenital Adrenal Hyperplasia (CAH)
Treating Congenital Adrenal Hyperplasia
Cook Children's Endocrinology Department
Cook Children's Pediatric Urology Department

Transcript

00:00:02

Host: Hello and welcome to Cook Children's Doc Talk. Today we're talking about congenital adrenal hyperplasia. Cook Children's is designated by the Cares Foundation as a Center of Excellence for Congenital Adrenal Hyperplasia. Joining us are members of the team, Dr. Paul Thornton, Medical Director, Endocrine and Diabetes Program, Dr. Blake Palmer, Medical Director Pediatric Urology and Surgical Director Kidney Transplantation. Dr Cortney Wolfe Christiansen, clinical child psychologist, and Emily Haddad, a licensed clinical therapist and social worker. Welcome to all of you. 

00:00:39

All: Thanks for being here. Thank you for having us, happy to be here.

00:00:43

Host: Congenital adrenal hyperplasia or CAH, is one of the most common inherited metabolic disorders. We know that there are two forms of CAH, classic and non classic. Non classic is a mild form of CAH and fairly asymptomatic, while classic CAH  is very severe and often life threatening. From birth, the classic form of CAH affects approximately one in 15,000 babies born each year. While we can touch briefly on the non classic form, I'd really like to focus on the classic form of CAH and the unique challenges faced when caring for children with this disease. Dr Thorton, as the medical director of this program can you take us through an overview of CAH?

00:01:25

Dr. Thornton: Yes, congenital adrenal hyperplasia CAH as we like to abbreviate it, is a condition in which there is an enzyme deficiency in the adrenal glands and as a result we get a deficiency in some of the most critical hormones in the body for example cortisol with in excess of the sex steriods, particularly the androgens being produced. And why this is very important is that cortisol is essential for life and in times of critical illness our bodies make more cortisol in order to help us survive and children with CAH are unable to do this and hence they can have life threatening adrenal crises which can be manifested as hypotension and hypoglycemia and can be critically dangerous.

So with classical congenital adrenal hyperplasia there are 2 forms. there are those who are missing the cortisol and that would be called simple virilizing, and then 75 percent of the kids are missing both cortisol and aldosterone which is called salt wasting CAH, and that is by far the most dangerous of the 2 conditions.

00:02:31

Host: Dr Thorton, your specialty is endocrinology and Dr Palmer yours is urology can one or both of you talk about why you've combined the 2 programs and what that means in terms of patient care?

00:02:43

Dr. Thornton: Prior to forming the congenital adrenal hyperplasia clinic patients were seen isolated in either the urology clinic or in the endocrinologist clinic. And all of the patients, or many of the patients, had complex conditions that require the intervention of both urology and endocrinology. And in both clinics we operated in silos we did communicate with each other but we didn't provide all the psychosocial and emotional support that's required. So we had an opportunity several years ago to form a multidisciplinary clinic that was based on a model that had been performed in Oklahoma and we set that up here and so now patients come see us, they see us in one clinic. They see the urologist if needed the endocrinologist when needed the clinical therapist and the social worker and we get to take care of all of their needs both in terms of medical, educational. and psychosocial. And so really what we've been able to do is take a multidisciplinary team approach and we believe, dramatically improve the quality of care that the children get.

00:03:50

Dr. Palmer: In these cases, there's a great deal that I can learn from Dr Thorton and the endocrinology team about how I can best help take care of the patient I'm seeing at the same time that he is. There's a lot of patients unfortunately who do need to see multiple different doctors within the hospital and there’s some who just need to see a neurologist. But in this case there's a lot of discussion between the medical teams and the surgical teams that we can really produce a better product for the patient we feel.

00:04:17

Host: So basically this is a multidisciplinary approach but not really in the traditional manner. Rather than each of you meeting individually with a patient family you all come together as a team and meet with the family at one time. Why this approach and how does it benefit the care of patients and their families?

00:04:37

Dr. Thornton: Okay I'll take that one. The key thing about seeing the patients in the multidisciplinary clinic is that we meet all together at the beginning, we discuss the past history, our anticipated plans and issues for the day, and at the end of the day we meet again and do a wrapup,  making sure that we covered all the options. So some people would describe it as interdisciplinary others as multidisciplinary. In essence, we tailor the visits to the patients at each visit.

00:05:06

Host: And the benefit to the patients and families then is that they don't have to make as many visits or they don't have to spend like an entire day or how does that help them?

00:05:17

Dr. Thornton: The best benefit I think for the patient is that they get to ensure that we have complete communication. Everybody's on the same page, we’re all working together as a team for the benefit of the patient. Of course the secondary benefit is that they come and see us in one day. The visits are a little longer but they get to see everyone. But I think more importantly when we were seeing these patients individually in clinic we did not have the psychosocial support. There wasn't time for the proper education and so we're doing sort of fully integrated health care for those patients and at the end of each day I think the patient leaves better educated understanding their condition more comprehensively and thus better prepared for the difficulties that they will face out in the world on a daily basis.

00:06:01

Host: So how often does your team meet with each family?

00:06:05

Dr. Thornton: Typically we see patients 4 times a year, every 3 months. However in the newborn period where there's a lot of decision making that has to be done a lot of education that has to be done we would see the more frequently and then perhaps later in mid childhood or adolescence we would see them less frequently when their medical conditions are stable, when the families are very comfortable with what they're doing and when the child or adolescent has a good understanding. So the frequency varies from perhaps once a month in the initial newborn period to maybe twice a year.

00:06:40

Dr. Palmer: And different different members of the team may have more of a role at different time points and their course, depending on how their health is going also. For instance, from urology we may be more involved in girls early on in some the surgical decision making like not to have surgery or to have surgery and discussing those pros and cons. We may be more involved later on when they start to go through puberty and start mid season the females and then as they get older in teenage and young adulthood talking about sexual questions that they may have. For the boys we may not be very involved or needed much early on, but then when they go through potty training and then later on after they go through puberty, be more involved in those patients. So it certainly depends on the patient and depends on where they are in the process.

00:07:24

Cortney Wolfe-Chiristensen: Behavioral health is also available more frequently than the scheduled ordinary visits so depending on the experience of the family and how they're coping with their child's illness, behavioral health is available as needed.

00:07:38

Host: So we know that there are some very serious conditions caused by classic CAH, can you talk about the challenges and risks each one presents and how they're treated?

00:07:47

Dr. Thornton: From a hormonal perspective, the biggest issue we have is the risk for acute adrenal insufficiency where the body is not able to adjust to the stress of illness and make more cortisol. So we focus on teaching our families how to identify endocrine illness. How to increase their dose of steroids to take into account the increased need of the body and then when the child is not doing well how to do a intervention such as an emergency injection of hydrocortisone and how to get to the hospital quickly. When we give our families educational materials and emergency letters so that when they go to the emergency room they can give them to doctors who are not as familiar with adrenal insufficiency and adrenal crisis in congenital adrenal hyperplasia. Blake.

00:08:35

Dr. Palmer: So for the most part for most for kids an acute urologic or a problem or infection are not very common but they can occur and helping families be able to identify when that's happening and get them treated appropriately is important. In my opinion though, for kids that are born with congenital adrenal hyperplasia especially in the girls, who may have differences and their families anticipated appearance of their genitals or their female anatomy all of these families, maybe not the kid because the kid is usually very healthy, but the families have a crisis and that's where our behavioral health team is really important and I think should speak to that.

00:09:15

Cortney Wolfe-Chiristensen: From a psychosocial perspective, like Dr Palmer said, when these kiddos are born the parents describe the birth as traumatizing. Oftentimes the baby is born there not expecting the baby have atypical genitalia, and the baby gets whisked off to the NICU, mom's miss out on that skin-to-skin contact and that bonding that happens immediately after birth. And then the other thing that they report is just feeling isolated because when your child has a difference in their genitals it's not very easy to talk to other people about that. And we know the parents of these children have experienced levels of posttraumatic stress symptoms that are equivalent to parents whose children were just newly diagnosed with cancer. But when your child was just diagnosed with cancer you know you have an entire community that supports you in people making t-shirts and bracelets and bringing you food. And yet when you have a baby born with different genitalia you don't have that support. And then the last thing especially now with social media and post, “We’re on our way to the hospital to have a baby,” and then people are wanting to know did you have a boy or a girl? And our parents also report you know being inundated with text messages and people not being happy with just hearing it's a healthy baby.

00:10:27

Dr. Palmer: And there's a lot of challenges from the health care standpoint too. And this is why one of the things that we think is really important as part of our team is not only educating the families and educating the patients as they get older about congenital adrenal hyperplasia, but it's really important to us in a rare condition such as this though that can be very impactful is educating the health care community. One of the biggest challenges we have is that this is not common and so they'll be born at a hospital where often the nurses never had a kid who's been you know born with congenital adrenal hyperplasia, or CAH, and is unfamiliar with what what's going on what this is and so they are not purposely but they are because of their own uncertainty their at their lack of confidence in what they're doing they're not able to provide the good support that they need to and the parents sense this. And the parents talk about that later about the discomfort the nurses had with it. They feel like sometimes it’s because their kid had different anatomy. Often what it really is, is just the nurses or the health care staff just being uncomfortable with the diagnosis entirely.

00:11:30

Host: So what kinds of surgeries might be considered for female patients with CAH, and is there an optimal time in terms of overall health and recovery?

00:11:39

Dr. Palmer: So it's really important when we talk with our with our families who have congenital adrenal hyperplasia. The females often were exposed during embryology and during development when moms are playing with them to hormones that were different than what would cause their female genitalia to develop optimally and so sometimes this means that they are virilized or exposed to more male type of hormones, doesn't mean that they're males but it just means that they saw a male type of hormones, and this can cause changes right? And so they're on the outside and having a separate opening for they pee from and where the vagina would be, those can be fused together and so externally it looks like there's only one opening. There is still a very normal vagina, normal uterus in all of these girls with CAH. But it just may not be apparent from the outside. They also can have those hormones that make their female genitalia look a little different, more masculinized, and their clitoris can be somewhat enlarged. These can vary widely.

Some of these girls may have just very minimal differences some of them can have profound differences. And so things that are really important for us is being able to explain to the family and for us to understand exactly what their female anatomy is like and understand and help the families understand what are the important functions that the female internal and external genitalia and urinary system are supposed to do and if those functions will be different based upon the anatomy that they're born with. In some of those cases we will talk about procedures to separate the opening where they pee from and where their vagina is, to minimize their risk for any urinary complications and then later on to allow for typical vaginal functions that a, you know, young woman or a fully functioning adult woman may desire to have.  If not having those procedures wouldn't necessarily be the case or be optimal certainly there are some times during their lives where we would recommend that the servers are more optimal to be done but certainly recognizing that and a lot of times the surgeries and would not be required or necessary or necessary at those times. So early on in development, less than 2 years of age, that's a time where we can do these procedures very safely and successfully but have minimal impact on the patient's ultimate development, their recall of these procedures that are done.

The families in those cases would be making those decisions. But there are definitely times we counsel the families and give them the option is to wait until that patients older that patient could be after puberty into young adulthood before they choose to have those types of procedures. There are lots of reasons why families have chosen one option or the other and certainly lots of good reasons why parents have chose not to have surgery at all. And as long as this doesn't have any functional deficits for them and they're not having problems with urinating or urinary tract infections this is a child who can be very healthy whether they had surgery or not.

00:14:36

Host: So in terms of the surgeries, Emily. there's a lot of controversy around what kinds of surgeries may need to be done, as we just talked about, and when, particularly in girls. So why is the controversy?

00:14:47

Emily Haddad: Historically these procedures were completed on females with what we call concealment-centered model. What I mean by that is that parents were counseled to not educate their daughters about surgeries that took place when they were infants. Our team prioritizes a patient and family centered model of care we discussed the options of pursuing surgery in the option of not pursuing surgery with each family over several visits we also share with families that there is controversy about the autonomy of the patient and the full informed consent. We meet amdcounsel each family during several office visits as I mentioned before any decisions are made then the importance of full disclosure and education of the patient as the agent as it's appropriate is prioritized by our team.

00:15:29

Dr. Palmer: We also think it’s extremely important during these times is that they get education from the different members of our team independent of the surgeon also. And then we think it's really important that they seek and are provided information in any way we can from other families who've gone through making these decisions and who have they've had an experience right? They have an older child or their family's gone through this where they can provide a very different perspective than we can as health care providers their families who've been through this and we try and and make sure that they have the opportunity to talk with families who’ve chosen not to have surgery and what was that experience like for their family, and why was that right for them. And parents and families who’ve chosen to have surgery or even patients who were older and had surgery and why that may have been right for their family and right for them as well. So independent and lots of education for different sources are things we think are important.

00:16:17

Dr. Thornton: In addition we encourage them to contact the Cares Foundation which is a family support group that advocates for children with congenital adrenal hyperplasia and stimulates open discussion and helps direct patients into research protocols. So we would recommend all our families would go and look up at their website at www Cares Foundation dot org, where a lot of useful information and a slightly different perspective than they might hear from us can be found.

00:16:49

Host: So all of this combines to no doubt create a lot of emotional, mental, social and behavioral challenges that both parents and their families have to cope with. Current guidelines emphasize the importance of mental health in CAH  patients, so Emily you and Cortney are well versed in providing psychosocial care and services. Who's involved and how are patients and family members assessed and managed?

00:17:14

Emily Haddad: Our team prioritizes the behavioral health team meeting independently with the families. We’re also available by phone calls, email messaging. We use a comprehensive psychosocial approach to our assessment which means we take in the well being of the entire family as we address the individual with CAH. We attempt to understand every family's cultures so we can utilize that family’s strengths and coping with their child with a chronic illness. We know that certainly having a child with a chronic illness can lead to a lot of external stress, anxiety, depression, but with adequate interventions and support families can do very well coping with their child with CAH. 

00:17:51

Host: And do they meet here, or do you have support groups here on site?

00:17:56

Emily Haddad: Since the start of our clinic we have hosted family support group meetings and we also attempt to introduce families in clinic when it's appropriate. Sometimes this can be really helpful for one teen who feels very isolated to meet perhaps another teen who also has CAH.

00:18:13

Dr. Palmer: This is one thing that I really think this is kind of fun and it it's if we don't have a chronic condition that's rare we don't ever think about this. But if you live your life and you have something that really identifies you that's really core to yourself but you've never met anybody else who's like that you maybe have heard other people or whatever it can be pretty neat to meet a bunch of people. And for new families who have a new a kid with a new diagnosis they're learning about the opportunity to meet and see some excellent well developed healthy kids who are older can help ease some of that uncertainty about what's gonna happen there kid because now they can visualize, “Oh, this is a kid who’s in high school, who's very normal, he's got good grades who goes to school, who has these things,” and they see oh, it's okay right. And that's one of the things that I think that our team in these kind of groups does a great job with. As we don't have anybody who will be a teenager and just have never met anybody else was CAH. Or families who've just never had the opportunity to talk with somebody or meet somebody. It may be something that we underestimate, and I underestimated until I saw it actually happening, and it's it's a pretty good thing.

00:19:20

Cortney Wolfe-Chiristensen: For our support groups we generally separate our parents from the children so the children got to have a fun afternoon of activities that are related to CAH  but they might not necessarily realize how much they're learning about CAH  at the time because they are having so much fun. And then on the parents side we usually bring doctors Thorton and Palmer in for a little while to answer any medical questions that the family has and then we kick them out of the room and the rest the support group is just parents talking to parents and bringing up their concerns and we try to keep it as a really positive environment and really focusing on families coping skills and their strengths and what has worked for them.

00:20:01

Host: Fantastic. So Cortney, you're actually involved in research with regard to helping parents pf kids with CAH cope with their feelings about this diagnosis, can you tell us a little about the study?

00:20:11

Cortney Wolfe-Chiristensen: Sure we actually have an ongoing study right now that is supported by NICHD and what we're doing is we're developing an intervention that can be accessed online and the goal of the intervention is to help parents cope with the uncertainty that they have when their child is born with CAH. So this intervention was originally developed for parents of children with type one diabetes and then we adopted it and made it an in-clinic intervention for parents of children newly diagnosed with cancer and then this step we have adopted it and put it online so that it can be accessed by anybody at any time. And the first part of the project involved interviewing 30 parents of children with CAH  to really understand what their experiences were like and what information would be best to include in our intervention for those families who are going to be going down that road.

00:21:01

Host: Just to elaborate a little more what are some of the bigger concerns that a parent might have or a fear that they might have or things that they feel like they can't talk about with others?

00:21:13

Cortney Wolfe-Chiristensen: Absolutely I think that parents really struggle with finding the balance between seeking support for themselves and also their child's privacy. Right so trying to figure out how do we access and the adults in the community are in our family to help us but also allow our child to have the privacy that any child would have freight and to allow the child to make the decision about who he or she wants to disclose this diagnosis to. Really interestingly in the interviews almost everyone of the moms cried when discussing the delivery of the baby and actually we took that clinically and we have had a couple prenatal consults of moms who have suspected girls with CAH  and we've put together a letter, doctors Thorton and Palmer wrote one, and we send a letter to the mom's OB, to the pediatrician, and we give a letter to the family and it outlines what needs to be done. And when the baby is born if the baby does look like she has CAH it explicitly says you can leave the baby with mom to feed and bond normally and it tells them what labs to draw in who to call. And so that was something that happened in the midst of the research study because it was just so apparent that these moms really struggle. And then the other interesting thing. so the last question that I ask parents is what would you tell new parents of kids with CAH?  98 percent of them, moms and dads, all said, “It's going to be okay.”

The first year is really hard. They're trying to learn the diagnosis, how to take care of them, how to watch for symptoms of adrenal crisis. Iind of always being on their toes worried, but then after a year they fall into a routine and they understand things better and I had one mom who said when my child is out on the playground nobody knows now that he has CAH.

00:23:03

Host: So in the past there's been a big disconnect in care for patients as they transition between pediatrics to adult medicine, why is that and how does the CAH program at cook Children's address it?

00:23:13

Dr. Thornton: You raise a very important point. The literature would suggest that only 10 percent of adult patients with CAH get specialized care and this is very distressing and comes about probably because in the past this was considered a childhood illness and that when children became adults the would go through a period of time maybe where they didn't have health care or they would end up seeing a family doctor who would think, “Well this is just adrenal insufficiency we can handle this.” So historically the transition from childhood to adulthood has not gone very well. In recent years we’ve started to learn that as we have done a better job taking care of our patients and their lifetime survivals are now almost normal we need adult providers to be familiar with congenital adrenal hyperplasia.

00:24:08

Host: So Emily, at what age do children with CAH begin to transition to adult care? What is the process and what role does the child's primary care doctor play? 

00:24:18

Emily Haddad: We introduce our transition program to adult care beginning around ages 12 to 14. Depending on the child's maturity we work with the caregivers and our goal is to make sure that each patient fully understands the name of their disease, the disease process, medical and surgical history, risks associated with their condition, how to obtain their medications, navigate insurance, schedule appointments, what their emergency plans are. So essentially we try to transition all of the responsibilities from the parents, the caregivers, to the patient slowly over time. So we might make small goals at each visit to accomplish for the next visit.

Then along with Dr. Mary Cox we’ll transition the child into it adult care. It's important that we teach the child that although they do have a chronic illness they can manage this and reach all of their goals whether they be academic or career. We ensure that this child gains the responsibility at a young age so they can start working with their parents to gain that independence.

00:25:22

Host: So you work with the parents and the child a lot to to help the parents kind of let go and allow that transition, or is that just kind of normal?

00:25:29

Emily Haddad: Sure, so it's very normal for any parent of a child with a chronic illness to have anxiety or stress related to transferring those responsibilities to their child, so we support the parents and coping with that challenge and then also entrust that the child can learn these details and learn how to manage their health care.

00:25:48

Host: Of course as patients begin to enter adulthood they may start to consider having families, so what role does genetic counseling play in the care of patients and when should it be considered?

00:26:01

Dr. Thornton: When children with CAH  want to go on and have families there are a couple of issues that we have to really address. Number one is the importance of compliance and taking their medications in order for their reproductive health to be as good as possible. For example, if teenage boys and young adult men stop taking their steroids they can develop secondary tumors in the testicles that will impair their fertility. So whereas they may feel okay on a day-to-day basis and they may be lucky and not have any episodes of acute illness that could trigger an acute adrenal crisis they could impair their fertility. So number one is helping them understand that good compliance and following the medical guidelines will result in more likely than not normal fertility but not doing so increases the risks for infertility.

Genetic counseling is very important because the children need to understand the mechanism of transmission of congenital adrenal hyperplasia. It's an autosomal recessive condition and so they have two broken genes and they need to understand that approximately 1 in 55 to 1 and 60 of the population also has a gene that's broken for congenital adrenal hyperplasia. And so they need to understand their risks of having a child who could be affected more severely or less severely than they are. Thus, we believe it's very important to have a geneticist as part of the multi disciplinary team. A genetic counselor who can come in and help counsel the adolescents. We often do some of that ourselves but at the end of the day when they become an adult it's good to have that adult man or woman meet with the genetic counselors for final education and to make sure that they really understand the implications of their disease on future reproduction.

00:28:00

Host: So the team is also involved in research studies on the short-term outcomes of interventions for reproductive dysfunction. Dr Palmer, would you like to share the details?

00:28:10

Dr. Palmer: Yeah, excellent. We think it's really important and our ability to educate and give families an idea of what surgical procedures would hold for them in the short term but also in the long term. And this is just not great information that's previously been available. So in the short term, looking at just a family's acceptance of the external genitalia, whether they had complications or not, and so the the study that we're doing this with is at 13 different major pediatric centers who specialize in treatment and surgery in kids with congenital adrenal hyperplasia. And so we’re able to pool this into a study sponsored by the NIH that is the largest study on surgical outcomes of kids with congenital adrenal hyperplasia. In cases where we have rare conditions we think this is really important to be able to pool this to have accurate information that we can say is similar to what people can expect anywhere. The other thing that's really important is this study is being prolonged so that we will be able to provide long-term information. So really importantly, whenever we do procedures, especially if it's going to be something that impacts the woman's function but not until she's an adult, being able to follow those kids all the way into adulthood and be able to report back on what were those outcomes did they need any further surgeries. did they have any problems, we feel is extremely important. And so this study with continued followup, hopefully we'll be able to provide that information that's never really existed.

00:29:37

Cortney Wolfe-Chiristensen: And going along with that study we also have a simultaneous study looking at the parents and how parents are coping with their levels of depression, anxiety, stress, and trauma. And we're following those parents over time so we had baseline assessments and then after the patient surgery and now they're on yearly followup. This information is very helpful because we can use that to educate future families that it's typical for families to go through an increase in uncertainty prior to making surgical decisions. And then after those decisions are made that uncertainty comes down pretty significantly. And as part of the second part of the study we're also looking at behavior in children with CAH  and having their parents fill out behavior rating scales.

00:30:22

Host: So for pregnant women whose fetuses at risk of being born with CAH, what are the health risks to both mother and baby and how are those risks managed?  Doctor Thornton?

00:30:30

Dr. Thornton: There is very little health risk to the mom in terms of her own body and the safety of the pregnancy. Obviously the psychosocial risks of the anxiety of not knowing what the baby is going to look like and whether they're going to be critically ill and the newborn period or not are an ever present risk. However, to her health itself there's no real risk. For the fetus there is no inherent risk and no danger that you're not going to make it through pregnancy, the problems arise after labor and delivery when those hormonal deficiencies in cortisol become an issue or the excess hormones, the androgens, can have an affect on genital development. And so really what we focus on for ladies who are pregnant, who’ve been identified as being at risk is we focus on giving them a clear cut understanding of what will happen at the time of labor and delivery. In the next few days after labor and delivery we give them a plan that allows the physicians to be comfortable in allowing that baby to bond with its mother and gradually we arrange for them to come and see us in clinic so as they have knowledge of the future and what we find is that the anxiety of the unknown is the greatest problem.

00:31:51

Host: What is the long term outlook for CAH  patients?

00:31:55

Dr. Thornton: Medically, most CAH  patients should do very well. If we replace the hormones that they're missing, if we teach the families how to identify acute endocrine illness, and how to stress those appropriately, and we fix any of the problems that are causing health issues for example if a young girl has labia that are fused together obviously when the time for puberty comes along she's not going to be able to menstruate and get the blood out and so if we address these issues either by stopping puberty or by making an opening then we can generally prevent major problems that will have an impact on their health.

So what we find is the biggest impact that they have is the psychosocial and emotional stresses of maybe being different, of having an acute life threatening illness, even though they know that if they treat it appropriately they can eliminate most of the risk. However, sadly, every year we hear of someone who dies with adrenal insufficiency, whether it be from congenital adrenal hyperplasia or other causes. And so this is an ever present threat that the families need to understand.

00:33:10

Emily Haddad: As doctor Thornton mentioned, the long term outlook for CAH patients is good. With proper support and proper interventions individuals with CAH can live a very fulfilling life and reach their greatest potential.

00:33:22

Dr. Palmer: And our role with each different aspect that we provide is just to make sure that from whatever their individual goals are for their life that they aren't held back by CAH. 

00:33:33

Emily Haddad: What we've learned from our patients and from patient advocates is that when people are fully informed about their conditions and their medical and surgical history they do better. So we, our, team prioritizes the integrity of the individual by educating them fully on their own medical history.

00:33:50

Host: Fantastic. So is there anything else that any of you would like to add as we wrap up?

00:33:55

Dr. Thornton: One of the things that we found is that the families are faced with making some very difficult decisions. And what we've often found is they don't know the right questions to ask. So one of the approaches we take as a team is that when one physician or clinical therapist or social worker will say things to the family those of us in the room might ask some of the questions that we know the family should be asking but they're not asking because they don't know to ask those questions. And so typical things would be if we were having a discussion about the medical necessity of a surgery I might ask the surgeon well could we wait till the child is 12 or 13 and defer the surgery until that time? And then the surgeon, or Dr. Palmer, would then go through all of the pros and cons of doing that. So by the family seeing us question each other not because we're doing it because we don't think they know what they're saying but really asking the question on behalf of the family it empowers them to ask questions that they might be nervous to ask.

00:35:00

Dr. Palmer: And I think that's an excellent point. And it's definitely an area that is different than how I run a lot of my clinics because usually it's just me talking with and back and forth of patients. Having Emily, Cortney or Dr. Thorton, or one of the endocrinologists or other people on our team in there and us having a little bit of a discussion in front of families also helps them be involved. And it's an excellent way for us to make sure that the things we want to get communicated across actually are getting community across. And what we need to understand as health care providers is sometimes a lot of the things we say may be more complicated than it sounds like when it's coming out of our mouths. And what's actually being understood is way more important than what we actually say. One thing that we think is important when we hear from patients and families and when we're talking about our job or our role, is educating other health care providers, whether it’s staff in labor and delivery units or primary care providers, is that families may have questions or may be uncomfortable and then maybe those providers those health care workers may not be comfortable answering things or may not be comfortable around them. And the things that I would want anybody who may come across a patient with CAH or a  family who has CAH to know is that they're healthy, that they really are okay, it's okay to talk to them, it's okay to say they're not familiar with CAH, it's okay to say that they don't know exactly what this is. But what we want to make sure they know is, is be able to say, “But we know of a team that will be excellent to help you.” And we're going to get that information for you, and we're gonna be there to help out not feeling like you don't know what it is. And that's a lot of our job to make sure that were available for everyone and and to provide that education.

00:36:42

Dr. Thornton: It's important for other primary care physicians and pediatricians to remember that they can call us through cook direct connect 682-885-1940, and within minutes have an expert on the line who can guide them through talking to a family at any given time. The immediate crisis is the concern over the ambiguous genitalia but the medical crisis happens anywhere from 5 to 14 days later with acute adrenal insufficiency.

00:37:14

Cortney Wolfe-Chiristensen: And we're trying to help the family so it's not a crisis.

00:37:16

Dr. Palmer: That's correct right this is a group discussion just like we had this is exactly how we doing clinic is that Dr Thornton's expertise in those areas are gooing to different than what mine are. And I'm going to advocate for these things and so it's a group process that we work with so good work.

00:37:34

Cortney Wolfe-Chiristensen: We speak about the trauma that some of these families experience. The good news is that the human brain can heal from trauma. So these families can have very good outcomes.

00:37:16

Host: Thanks to all of you for taking the time out today to talk about the CAH  program here at cook Children's. The work you do is amazing and so important to the patients and families you care for.

Thank you for having us. 

We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's please visit us at Cook Children's.org.

Listen Now

Dr. Heym gives insight into Total Therapy XVII and why this all important breakthrough in precision medicine and targeted treatment approaches offers the promise of more cures for acute lymphoblastic leukemia and acute lymphoblastic lymphoma patients.

Kenneth Heym, M.D.

Related Information:
About the Total Therapy Study XVII at Cook Children's
Cook Children's Hematology and Oncology Center
Cook Children's Oncology Program
Cook Children's Leukemia and Lymphoma
Cook Children's Hematology and Oncology Clinical Research

Transcript:

00:00:01

Host:  Hello and welcome to Cook Children’s Doc Talk. We're here today with Dr. Kenneth Heym, Medical Director of Cook Children’s Oncology Program. Dr. Heym specializes in the care of children with childhood cancers as well as being the medical director of oncology. Dr. Heym is also very actively involved in research focusing mainly on leukemia and lymphoma and has published several important works on the subject. Dr. Heym, thank you for joining us today to talk about Total Therapy Seventeen, the upcoming clinical trial for children with acute lymphoblastic leukemia or acute lymphoblastic lymphoma.

 00:00:38

Dr. Heym:     Thank you for having me here and it's my pleasure to be able to discuss this exciting work that's going to be something we can be a big part of here at Cook Children's.

 00:00:45

Host:  So can you start by giving us an overview of the Total Therapy Seventeen clinical trial.

 00:00:51

 Dr. Heym:    So acute lymphoblastic leukemia is the most common disease that we treat in childhood cancer. It has gone over the years from a uniformly fatal disease to one in which the vast majority of children will not only be cured of their disease but will go on to have the rest of their life just as before. So Total Therapy Seventeen is the upcoming trial for newly diagnosed patients with acute lymphoblastic leukemia, It is through the St Jude Children's Research Hospital in Memphis Tennessee, now, we have been honored to have an ongoing relationship with St Jude for probably the past twenty years. We participated in other clinical trials with them, We were actually the only institution in the world to participate in the Total Fifteen acute lymphoblastic leukemia protocols so we were the only other hospital that participated in an up front newly diagnosed trial for children with ALL with St Jude. Total Seventeen is really going to be a summary of all that we've learned about leukemia in the last decades really trying to maximize not only the existing therapies that we have for childhood leukemia but also incorporating so much new technology and some of the really cutting edge therapies that are being used, the goal being to cure as many children as possible obviously but also to try to minimize the side effects which can occur both during therapy and long term later in life. The goal is really to try to provide individualized care to each patient.

 00:02:15

 Host:  So you mentioned the long term what are the long-term risks for children?

 00:02:20

 Dr. Heym:     So children who survive childhood cancer are at risk for many long term health issues. For patients with leukemia some of the more important ones are due to their exposure to steroids as children. They do have a risk for issues with bone growth and bone health they have a higher risk for something called a vascular necrosis which is kind of a type of arthritis they're also exposed to medications that can affect heart function both in the short term and long term. We know that there's a lot of data coming out that survivors of childhood ALL have an increased risk for obesity and all the health problems that are associated with that. So as more children are being cured part of the main focus of our treatment plans is to not only continue with those good survival rates but to also minimize the exposure to toxic drugs and decrease the long term late effects that patients are having. And by incorporating a lot of the newer technology and newer types of medications, which Total Seventeen will include, we’re able to remove a lot of the old type chemotherapy that really attacks the entire body and focus a lot on treatments that just will attack the leukemia.

 00:03:24

 Host:  As one of the five children's hospitals participating in the trial what role does Cook Children’s play?

 00:03:29

 Dr. Heym:     Well, we have had a very long established successful relationship with St. Jude participating in leukemia trials with them both for newly diagnosed patients as well as relapse patients for both acute lymphoblastic leukemia, or ALL, and acute myeloid leukemia, or AML. We are a large center here we see a large number of newly diagnosed patients with ALL and so I think we will certainly contribute a fair number of patients to the study and provide a lot of data. I also think we bring a unique aspect to the protocol in terms of the collaborating sites because we have worked closely with St. Jude before and as mentioned before we were part of the Total Fifteen protocol for acute lymphoblastic leukemia so we can serve I think as kind of an advisory role as well to some of the other collaborating sites.

 00:04:17

 Host:  How is being on a Total Seventeen protocol different from being on a standard treatment regimen for leukemia?

 00:04:24

 Dr. Heym:     I think participating in the Saint Jude protocol is allowing us to really provide our patients with access to all of the most cutting edge state of the art therapies for ALL, Total Seventeen will provide a patient with access to many things that may not be available otherwise. Number one is there are going to be a lot of biologic, genetic, and molecular studies being performed on the research side through Saint Jude that are going to enable us to learn much more about each individual patient's disease so that they can each be treated more appropriately and in a more personalized fashion. Being on Total Seventeen will also allow patients the potential opportunity to receive immunotherapy which allows the body's immune system to be utilized to fight the cancer itself and a lot of times will have many fewer side effects both short and long term than conventional chemotherapy. It also incorporates newer ways of using standard chemotherapy drugs that will hopefully allow them to have their maximal effect with a decrease in side effects.

 00:05:24

 Host:  So, how do genetics affect the way children and young adults tolerate and respond to the treatment of childhood ALL and LLy?

 00:05:31

 Dr. Heym:     So genetics are really playing such an important role. We've known for years that the genetics of a patient's leukemia give us insight into how aggressive the leukemia is going to be and how it needs to be treated. We actually will put patients into different risk categories based on the genetic aspects of their leukemia. We're also learning though is that the different genetic make up that all of us have affects our ability to tolerate chemotherapy drugs, how we break those drugs down, and we also know that there are certain genetic changes seen in people that will make them more prone to having side effects from specific chemotherapy drugs. So as part of Total Seventeen in addition to the therapy aspect there's also going to be testing looking for some of these genetic changes that might identify children that are going to be at higher risk for having potentially life altering side effects so that their doses can be adjusted appropriately and they can still get the anti leukemic effect that's desired but that they'll be at much less risk for developing some of the debilitating side effects that can occur later on.

 00:06:32

 Host:  So can you talk a little bit about how precision medicine can, one, further reduce the risk of recurrence and, two, reduce the short and long term side effects of treatment?

 00:06:41

 Dr. Heym:     So individualized therapy or precision medicine really is nowhere better utilized than in acute lymphoblastic leukemia. There are certain clinical and genetic factors that for decades we've been using to really put patients in a specific risk category so they can get what we thought of back then as individualized therapy. As we're learning much more about the specific genetic make up of not only leukemia but of each individual patient and how they're gonna react to specific medications and their risk for side effects we are really able at this point now better than ever before and I think with the resources and the research going on at St Jude here at Cook we will be able to as part of Total Seventeen provide precision and personalized medicine for ALL patients in a way that more standard therapies cannot. And so we will be doing a lot of testing that will not only identify how aggressive the leukemia is going to be and how we will need to be treated but also which drugs and in which doses are going to be the most important and the most appropriate for individual patients. The ultimate goal of this obviously is to cure as many patients as possible but we also, and I think just as importantly, we don't want to just care patients if they're going to be so debilitated from their therapy we want their life to be as full and normal as it can be and so I think with this precision approach the goal is simply to give each patient as much therapy as they need but no more.

 00:08:02

 Host:  Are there any initial case studies or patient family testimonials at this point?

 00:08:06

 Dr. Heym:     Well, Total Seventeen has been open at St Jude now for quite some time and so far it has been as successful as all the preceding Saint Jude studies. We have had many patients here at Cook Children’s that have participated in St Jude trials as part of our collaborations that have had you know incredible success in response and as mentioned we were the only other institution to participate in the Total Fifteen protocol. And, we have many patients here who we are following now many years off therapy who are disease free who clearly benefited from the questions that were being asked for that treatment. And so we're very excited to be able to continue our collaboration with St Jude because it is really allowing us to provide our patients with the most cutting edge therapies. We know that how we're going to be treating here Cook Children’s is second to none.

 00:08:51

 Host:  When does this trial open and who is eligible for the trial?

 00:00:01

 Dr. Heym:     We are in the process of kind of negotiating all of the final aspects of getting the protocol approved at Cook Children’s. There was already an amendment at Saint Jude so they are already working to try to improve the protocol even though it has been open very long they're very attuned to making changes in real time. We are hoping that the protocol will open and will be able to start enrolling patients potentially as early as September or October of this year. And this will be a trial … one of the reasons it's called Total Therapy is because other organizations will break up protocols for patients with acute lymphoblastic leukemia into high risk protocol, low risk protocol, and T-cell ALL protocol, the St Jude protocol is all encompassing and so, all newly diagnosed patients older than one year of age at diagnosis with acute lymphoblastic leukemia, all types will be eligible for the protocol. And so we think we'll be able to have many patients participate that will enable us to learn even more about this disease and how we can treat these patients better.

 00:09:55

 Host:  So what do you expect or hope for in terms of the outcomes from this trial?

 00:09:59

 Dr. Heym:     I think if you were gonna simply ask what the ultimate outcome would be it would be obviously that we are going to cure more patients with childhood acute lymphoblastic leukemia than ever before. The cure rates for ALL continue to increase. The St. Jude Total Fifteen protocol that we participated in at the time it was published produced the highest cure rates for a child today with ALL. So I think the simple goal is to cure as many kids as possible, but I think, as mentioned before, just as important we want to try to minimize the side effects that these patients experience because sometimes you will cure a patient's leukemia but they will have devastating debilitating issues that they're gonna have to deal with the rest of their life. So I think by utilizing the newer types of treatment, namely immunotherapy, cellular therapy, and also trying to individualize how we dose chemotherapy and assign chemotherapy based on genetic factors I'm hoping that not only will the majority of children continue to survive but that they will be leading as active and fulfilling and really have their lives be minimally if at all limited by what they went through as a child.

 00:11:01

 Host:  So I have one last question before we close which is why should I, or anyone really, care about this trial?

 00:11:08

 Dr. Heym:     I think this is a trial that everyone should care about because the hope is, and if we continue to follow suit with our relationship with St Jude, that again the vast majority of children with acute lymphoblastic leukemia will continue to be cured I think that we should also care locally because here at Cook Children’s we are going to be able to continue to provide our ALL patients which is the majority of our oncology patients with therapy that is unparalleled anywhere else. This is going to be a treatment that will allow our patients access to the most state-of-the-art, up-to-date modern therapies. And so we don't have to feel that any of our patients are gonna need to go to another institution to get something they need. We are really going to be able to provide the patients in our local region and also our referral base with therapy for ALL that is really second to none.

 00:12:00

 Host:  Dr. Heym, we really appreciate you taking the time to talk to us today about this very important advancement in caring for children with acute lymphoblastic leukemia and lymphoma and thank you for all you do here at Cook Children’s and for kids everywhere.

 00:12:12

Well, thank you for having me. It's a pleasure and we're very excited about what we're able to do here and only know that things are going to improve in the future.

00:12:21

 Host:  We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children’s dot org.

Listen Now

Go inside the challenging world of pediatric renal transplant with Dr. Robert Gillespie and Dr. Blake Palmer and explore how their unique approach goes beyond traditional care. 

Robert Gillespie, M.D.
Blake Palmer, M.D.

Related Information:
Cook Children's Nephrology and Dialysis
Cook Children's Renal Transplant Program

Transcipt:

00:00:01

 Host:    Today we're talking with doctor Robert Gillespie and doctor Blake Palmer of Cook Children’s Renal Transplant Program. It's very busy in the Child Life Zone today so you may hear a little background noise. And before we get started just a little background on our guests.

 00:00:16

 Dr. Gillespie is the medical director for nephrology and kidney transplantation and Dr. Palmer is the medical director of urology here at Cook Children’s. Doctor Gillespie earned his medical degree from the University of Texas Medical Branch at Galveston and completed his fellowship at University of Washington Seattle Children’s. Dr. Gillespie has written extensively for peer reviewed medical publications and has given many presentations to medical groups around the country. His professional activities include international outreach programs development of computer based tools for nephrologists and he has actively participated in numerous research studies.In the summers he serves as a camp doctor for Camp Reynal a summer camp for children with kidney diseases.

 00:01:01

 Dr. Palmer earned his medical degree from University of Oklahoma and completed both the research and clinic fellow at University of Oklahoma department of pediatric urology. He is board certified in urology with a subspecialty certification in pediatric urology. His work has been published in multiple peer reviewed journals and he's a nationally recognized presenter and a member of the American Urology Association, American Academy of Pediatrics section of pediatric urology, Society of Pediatric Urology, American Academy of Pediatric Urologists, Society of Fetal Urology, and the American College of Surgeons. He has special certification by the American College of Surgeons in fundamentals of laparoscopic surgery.

 00:01:45

 Welcome, you are both clearly very busy so thank you for sitting with us today.

 00:01:48

 Dr. Palmer:      Our pleasure.

 00:01:49

Dr. Gillespie: Yeah thank you.

 00:01:50

 Host:    So, doctor Palmer, for over a quarter of a century Cook Children’s kidney transplant program has been breaking ground in kidney transplants and is currently the second largest renal transplant program in the state serving not only children in Texas but in surrounding states as well. The program is also a recognized center of excellence by Optum and UnitedHealth but one of the really unique advantages of this program is the team approach between urology and nephrology can you tell us a bit about your partnership and how it benefits pediatric patients.

 00:02:22

 Dr. Palmer:      So I'm happy to talk about our program here. We're really proud of our team approach, we have a team of dedicated pediatric nephrologists and we work with our pediatric urology team very closely and which myself as a specifically trained in renal transplant a specific interest in this area, the benefits and what makes us different than a lot of programs is that we don't have just transplant trained surgeons who are helping out on these patients and these procedures. By having dedicated pediatric surgeons who work with kids all the time, we bring a different aspect and different approach to these kids. They're not just kids with kidney failure their kids first and so were able to take care of them in unique ways that really contribute to things that are different about kids and adults.

 00:03:05

 Adult transplant patients often are patients with diabetes and hypertension and that actually makes up very few of the patients in a pediatric transplant program. Many of them are long time urology patients that I get the follow all the way through doing everything we can to prevent the need for transplant but then when it comes time for that, being able to provide that complete circle of care for them. And this also allows us to be very comfortable with the unique aspects of very tiny kids in renal failure who need a transplant which are very foreign and very different for adults surgeons when they when they come across these patients. These are things that are a little different in our program than they are elsewhere that are very specific for pediatric patients.

 00:03:45

 Host:    Thank you. So Dr. Gillespie, both acute and chronic kidney disease can lead to end stage renal disease, or kidney failure, but there are differences in the causes between children under 6 and those from 7 to 20 can you elaborate on that?

 00:04:00

 Dr. Gillespie:   Certainly. So in children under 6, the most common cause of kidney failure is congenital anomalies of the urinary tract and and this is something that really distinguishes us from adult programs because as Dr. Palmer's mentioned adults largely developed kidney failure from hypertension and diabetes but in kids these congenital anomalies greatly complicate things because there's not only the medical side of the kidney failure but also the anatomic features that they often need a great deal of reconstruction of the urinary tract that sometimes has to be done in staged procedures and so they need very close collaboration with the urologists as well as we have to try to optimize their growth and nutrition, so in the midst of all this we want to be sure that they can grow and develop as well as they can. And that makes for a very complicated setting that requires a very multidisciplinary team.

 00:04:50

 In the older kids, say the 7 to 20 age range they more commonly have auto immune diseases things like focal segmental glomerularsclerosis, hemolytic uremic syndrome, lupus, these kind of things. And so those require a lot of medical treatment and a lot of input from the from the nephrology team and often even rheumatology gets involved as well.

 00:05:08

Host:    So regardless of the cause, what are the biggest challenges for patients their families and even the primary care providers and what are we doing to ease them?

 00:05:18

 Dr. Gillespie:   There are so many challenges these families face it's hard to know even where to start but when a child has a chronic disease they have many doctor visits, they have hospital stays, this is disruptive to the family. The parents often have other children at home they have to take care of, it’s disruptive to their school schedule, it's disruptive to growth, and so we try to put all these together and really a multidisciplinary thing that looks at how the care of the whole family. And family centered care has always been one of the key goals at Cook Children’s.

 00:05:52

 And so we try to bring in the family members as much as we can. We have social workers that work with them to help find support resources for them. We have Child Life specialists that work to address the child's needs as well as the siblings, and we try to bring the siblings in and then educate them on the child's condition. Try to explain to them why the sibling is getting more attention than the others, often try to deal with those issues so that there's not more stress in the family.

 00:06:13

 We have dietitians who help to optimize their nutrition, and, um, first we have a fantastic Medical Center with a huge number of resources to support the parents and the children and I constantly get feedback from my familyies about how wonderful their experiences are here, that all the different things like the Child Life Zone, the parent support facilities, the different people that come out, people are always telling me how much they like that, how much they appreciate it. I think most of all the comment I hear is that people really appreciate how the staff here all care about them, that everybody regardless of their position throughout the hospital throughout the outpatient side that the staff are always there for them and some of the people who've had experience at other institutions have commented how much better their experiences here and they really appreciate that.

 00:07:00

 Dr. Palmer:      Yeah, and one of the other things I think is pretty neat, Dr. Gillespie is being humble about the approach they take, is a lot of kids and a lot of the families talk about the camp experience that they get each year and it's a time where the kids with chronic kidney diseases can all come together, their parents get a break for a week which is no minor thing, and they can do a lot of the things that they may have been limited on otherwise. They get to have the normal kind of camp experience the best they can and they’re with a bunch of other kids where they're not singled out as the kid who has kidney problems or is sick or otherwise they're just like everybody else and it's a really neat experience and Dr. Gillespie’s brought me along to do that now and they do a great job with them.

 00:07:36

 Host:    So Dr. Gillespie, it's my understanding that a kidney transplant is the preferred treatment for children and teens with end stage renal disease over dialysis and other treatments, what are the advantages and why, does this include preemptive transplants?

 00:07:51

Dr. Gillespie:   Yes it does and for most patients a kidney transplant offers the best quality of life. It offers the closest thing to a normal life and while dialysis is a great thing and certainly has saved countless lives, in the long term we always try to get our patients towards transplant if it's at all possible because their just is more of a normal life. When you literally have a regular kidney inside your body that's functioning like a kidney that's as close to having your normal healthy original kidney as you can.

 00:08:18

 And so transplant patients typically after the initial period once they're settled down if everything goes well they may only have a doctor visit every month or 2. They may get labs once a month or so and that's a lot less than dialysis where you're either doing dialysis at home every night or you’re coming to a dialysis center 3 days a week, and those kind of things interfere with school, they interfere with other activities, you have to have some type of catheter dialysis access sticking out of your body, and all of those things go away when you have a transplant and it really makes for a wonderful thing for the kids.

 00:08:50

 Host:    So Dr. Palmer, there's been an uptick reported in the number of kids diagnosed with end stage renal disease, particularly in younger children, at the same time the number of donors has remained constant and the waiting list is growing, why do you think this is and what kind of impact or challenges does this pose for kids on the waiting list as well as for the medical team?

 00:09:12

 Dr. Palmer:      There are numerous reasons why we see that there are more kids diagnosed with end stage renal disease now. A lot of it has to do with advances in care of kids who are born with congenital anomalies in the NIU who are able to live and progress but may still have chronic challenges, um, as they grow older. The impact is tough because when they're on the waiting list the hardest part is - it's a waiting list. You don't know when your number's gonna come up for some people this can happen within weeks to a month and for some people, especially depending on their blood type, it may actually be a year or 2 so we we do everything we can to make sure that they're healthy, they're informed and that we're we're doing our best job of selecting the best kidney to have a successful outcome for them so that they can move past this chronic kidney disease or need for dialysis

 00:10:00

 Host:    So what about living donors? It seems like it would be easy to find a match in a family is this not the case?

 00:10:06

 Dr. Palmer:      Living donors are an outstanding option. It offers kids who get a kidney transplant potentially better outcomes necessarily than a typical cadaveric donor, however there are challenges with this, certainly. Someone in the family has to be a match, but also has to be healthy and make the decision with something we like to say is something we would all obviously like to have the opportunity and would always be able to do, but there's many reasons why this needs to be someone who is exceptionally healthy who it there is not going to be any negative impact for them so that we can have 2 very long healthy lives and not where we're trading years on one for years on another.

 00:10:43

 So while absolutely an excellent option and something we always want to pursue when available, um, that's something we do very conservatively to make sure that there's as much respect for the living donors health and long term life as there is for the person who would be receiving that gift.

 00:10:59

 Host:    So doctor Gillespie, for those kids are lucky enough to receive a donor kidney what are the short-term and long-term risks versus outcomes for kids after renal transplant?

 00:11:09

 Dr. Gillespie:   Our outcomes are excellent and we continually meet or exceed national averages on several different measures for transplant outcomes. Our success rates are very high and we're very proud of those. The short term risks are mainly related to rejection of the kidney. When you transplant a kidney into someone their body recognizes it as a foreign tissue and will try to reject it. It essentially views it as an infection that needs to be eliminated and so we have to use a complex regimen of medications to turn down the immune system to prevent the body from rejecting the kidney. And that risk of rejection is highest in the immediate post transplant period. Over time the body kind of gets used to having that kidney there and the risk of rejection gets lower and the amount of medication that we have to use also gets lower. So that's the biggest short term risk. Long term the biggest risk is from chronic infections. Even though we reduce the amount of medication these children are on immuno suppressive medication for the rest of their lives and so that increases the risk of certain opportunistic infections as well of some of the latent infections that people have in their bodies that don't normally cause any problems in a person with a normal immune system but they can become very active and difficult to control when the immune system’s suppressed. And so we have protocols for monitoring for those infections and then treating them accordingly when we need to.

 00:12:29

 Dr. Palmer:      And I think it's I think it's important he said that. One of the challenges with a kidney transplant when you compare to patients on dialysis, is that a patient dialysis from day to day is not likely going to be in pain they're not gonna go into major surgery, whereas with the transplant they are. So a transplant is more like - we kind of explain - it's more like an investment. There's an upfront cost and long-term benefits. Certainly there’s going to be a little bit of discomfort, there is gonna be a hospital stay, they are going to be at risk for a pretty significant surgery immediately, but those outcomes when successful and that's why we have a rigorous evaluation process to select those patients who are going to be most likely to have the best success and do anything we can to reduce their risk prior and this is where we can have a really excellent outcomes that we see.

 00:13:09

 Host:    Dr. Palmer for younger patients is this the only transplant they'll need or will they require additional kidney transplants as their bodies grow?

 00:13:17

 Dr. Palmer:      So at this time, unfortunately for younger patients, we have every expectation that they will need an additional transplant in the future. An excellent outcome for a transplanted kidney would be somewhere between 10 and 15 years, and for kids who are transplanted in between the ages of 5 and 10 or 20 years of age we certainly have expectations for their life much much beyond that so an additional kidney transplant is definitely at the expectation what our current abilities are for transplants. It's getting better and better each year but at this point we're making lots of incremental improvements, um, it's going to be new technology or new medications or things like that that will allow us to make bigger leaps and which the hope is they may only need one in the in the future.

 00:14:00

 Host:    I know that when you're born the size of your heart is the size of your fist, so for a small child that's a very small heart because the the heart doesn't necessarily grow with or the heart may grow but all the parts don't grow is this the same with kidneys?

 00:14:15

 Dr. Palmer:      The kidney that's the size when you're born grows as you grow. In kids with a kidney transplant though it certainly varies a lot between the kids age who is receiving the kidney transplant and then the age and the size of the kidney that is being donated to them. So often especially like in living donors when it's a parent during to a kid this is a fully grown adult kidney that we're providing, the kid can benefit from that in many ways because when we provide a donated kidney we're only providing one kidney. Both of their kidneys are not working so if it's a really large kidney they may be getting the benefit of much more than just what one kidney their own size would be. However, sometimes if it is an unfortunate, where it’s a cadaveric donor or a child has passed away who is donating and the family has elected to donate their kidneys, there can be situations where that kidney that is donated then, can be a great and excellent fit for some of our very smaller patients but then also grow with them over time.

 00:15:09

 Host:    So Dr. Gillespie, what are the challenges kids who have had a transplant face as they age into the adult health care system?

 00:15:16

 Dr. Gillespie:   So as these children grow up they eventually become adults and they have to move into adult life and just as there are difficulties with transition into other things of adult life, like getting jobs and finding housing and things, having to transition your health care also contributes to that. Um, in many cases their insurance changes when they reach a certain age and they have to transition from a pediatric transplant program into an adult transplant program. And one of the things that we really try to educate them on early is about planning for this transition and developing their responsibility. In the pediatric world we hold their hands quite a bit and we send them lots of reminders, we do things for them, we make phone calls for them, all these kinds of things and we try to explain to them that as adults they’re going to have to do that themselves.

 00:16:02

 We also try to educate their parents to ease them into this responsibility in a sensible way, we don't want to just stick them out there and and set them up to fail, but we do want to introduce them to being responsible for some of their own things,  taking their medications, scheduling their appointments, going to their appointments, all these kinds of things. And we have a formal transition program for that and we partnered with an adult transplant program to help to ease the transition. And so we have a meeting regularly with the adult program and we look at all the patients who are reaching an age where they're about to transition and we share information between the 2 and when are they’re ready for their first appointment with the adult program our transplant coordinator actually walks them over there to the clinic and introduces them.

 00:16:45

 Dr. Palmer:      And other things that are great about this partnership is that I work not only with our pediatrics program but also with the adult transplant program there, and that adult surgeons on that side work with us as well so there's a lot where they're more familiar with a lot of our patients and then also in those kids who have unique kind of conjoined anomalies and had surgeries and reconstructions that are more common in pediatrics but not very common in an adult patient, we can be there as well to help with those understandings and kind of bridge those gaps. So the thing we like to say is when we send them along we're not sending them alone. we're still in an excellent contact there's regular communication and we work together on a near daily basis.

 00:17:25

Host:    So Dr. Gillespie, knowing that not all children diagnosed with end stage renal disease are eligible for a transplant, can you talk a little about why and what options may be available to them?

 00:17:37

 Dr. Gillespie:   So while we would like for all of our patients to get a transplant as you said for some patience it's not a good option. Some of the things that can come up would be infections. If they have an active infection we can't give them a transplant and suppress their immune system because the infection would become aoverwhelming. Malignancy, if they're undergoing treatment for cancer or if they've had recent treatment for cancer we work with our oncology colleagues they need to be cancer free for a good period of time - typically 2 years before we go ahead with transplantm again, to reduce the risk of reactivating that malignancy. Adherence is very important. With a transplant, if you don't take your medications and come to your appointments and get monitored your body will reject the kidney and you can lose it. And it's very difficult to get a second transplant. The first one is always the best one. Now with each successive one, the risk of rejection is higher so we want to be sure that families are very very adherant and that they're going to follow through with the many requirements for transplant that are present in the initial period. And sometimes we need to give family some time to develop that. Sometimes they need to stabilize some things like maybe they need to relocate closer to the transplant center or maybe they need to be waiting for somebody to finish school or something like that.

 00:18:48

 There's some other diseases that can recur in a transplanted kidney like lupus or FSGS. We want to be sure those things are under very good control before we move ahead with the transplants. In the small children, they may be physically too small. Generally they have to weigh about 10 kilograms or more to get a transplant because anything smaller than that they just don't have the physical size to accommodate a transplant and so we have to optimize their nutrition and try to get them to grow. And kids with renal failure often have significant growth problems so it may take them quite a long time to reach that 10 kilogram mark. And some families just make a choice that they would prefer not to proceed with a transplant. It's not very common but there are some families who feel very comfortable on dialysis and if their child is stable and doing well they may feel like they don't want to rock the boat and that they'd rather just stay with that thing go through all the complexities and risks associated with the transplant.

 00:19:43

 Dr. Palmer:      Yeah, what we find is it’s not very common that there is a child or situation that is never going to be possible for tranplant. There are many times like Dr. Gillespie said that it may not be the right time right now but as they age as they move through their illness cycle as the family caregivers’ situations change or improve, that we never kind of say never for anybody, it's that right now's not the time, we need to optimize the situation and then re-evaluate them.

 00:20:10

 Host:    So what does the future hold, Dr. Palmer, for pediatric renal transplant patients?

 00:20:16

 Dr. Palmer:      The present is really bright but we have a lot of hopes for the future. There's a lot of interesting and groundbreaking things that are occurring in the lab right now on the forefront. Like always, we want to see that there's new and better medicines that help us reduce the risk for rejection but while also limiting in decreasing the side effects that put them at risk for infections. So those are always things that we’re looking and hoping for. But some of the even the more exciting things are complete paradigm shifts and which instead of getting a donation from another person that you would be able to grow a kidney or tissue that does the work of a kidney in the lab and then be able to and implant that or transplant that back in yourself. Current day, we can grow kidney tissue and different types of tissue in a lab situation but these things are very delicate, we’re still quite a ways away unfortunately from this being a true reality that's going to impact health care but these are certainly things that are on the horizon.

 00:21:14

 Dr. Gillespie:   There's also some very interesting work going on in developing immune tolerance so that patients bodies will not recognize that kidney is foreign and would be able to just tolerate the kidney without so much medication.

 00:21:27

 Dr. Palmer:      And that could lead to kids who could get one kidney and have it for life.

 00:21:20

 Host:    Incredible. So what breakthrough would you like to see either of you, both of you, in your lifetime?

 00:21:38

 Dr. Palmer:      Dr. Gillespie always. has some good advice about being a kidney donor, so I think one thing that is a very tangible, very feasible, ready for action thing right now is that every person you know if you talk to one more person that you choose to be a, a kidney and organ donor and this could revolutionize the current people who are here right now who need a kidney for sure.

 00:22:01

 Dr. Gillespie:   I agree. The most exciting dream would be the ability to synthesize an individual kidney that they could take a sample of your DNA and make a kidney that was custom made for you. That's probably a long ways off. What we can do today is educate people about donating kidneys. About signing up to be a donor in the event that you pass away and also being a living donor and both of those are excellent donation options and when we see that every year the number of people on the list is getting bigger while the number of donors is staying the same it really underscores the need for that so we really want to get the word out to people: if you'd like to be an organ donor to talk to your family about it educate them about what your desires are and your preferences and you can actually register online if you go to donate life Texas on the website you can actually register right there online for yourself and indicate your wishes to be an organ donor.

 00:22:51

 Dr. Palmer:      Yeah, it's super easy. You can do it on mobile you can web, and it takes less than a minute.

 00:22:56

 Host: That's great advice and a great suggestion. What thing do people fear most that they need to not fear so they might sign up?

 00:23:01

 Dr. Gillespie:   The biggest fear that I've heard is people think that if they're listed as an organ donor that doctors won't try to save their lives and that simply isn't true at all. Discussion about organ donation does not come up until every possible effort to save the person's life and restore the function of their body has been exhausted, and so I've never in my career seen a situation where doctors said “well we can help this person but they’re a donor so let's let them go. It's not how it works. In order to be able to donate organs the body has to be functioning, so it would be contrary to the whole concept of donating organs if they were not making every effort to help that patient. There's also a lot of misconceptions about organs being stolen and there are some spectacular urban legends about people's kidneys being ripped out that really don't make any sense scientifically, that would not be technically possible, and so I try to educate people about that and clear up those misconceptions.

 00:24:00

 Dr. Palmer:      Yeah, I think one of the hard ones too is that unfortunately for people who are not living donors, these do come from a tragic situation where a person is passing away and the family that is going through that grieving process has a lot of other things that they're thinking about at that time. And so if it's not something that that person has talked with their family about before sometimes they’ll say

“we don't know what they would want” and so it's really important if you go to donate life and sign up you've expressed what your opinion is and so your wishes can be honored by those people and by your family and you can take the burden off of them for having to make this decision because it's a decision that you've made and it's going to be respecting what you wanted to happen for yourself.

 00:24:45

 Host:    Well thank you both so much for taking time out of your day today to talk with us.

 00:24:50

 Dr. Gillespie:   You’re welcome we're glad to be here.

 00:24:53

Dr. Palmer Yeah, it was a pleasure

 00:24:56

 Host:    Thank you. And thanks for tuning in to physician perspectives recorded in the child's life studios at Cook Children’s if you'd like to learn more about our program and research at Cook Children’s visit our website at Cook Children’s..

Listen Now

Dr. Stephanie Acord discusses how early identification and new diagnostic methods and therapies for children with mild to severe cerbral palsyare helping to improve life-long outcomes.

Dr. Stephanie Acord

Related Information:

Cook Children's Neurosciences Movement Disorders Research

Cook Children's Neurosciences

Transcript:

00:00:02

Host:     Welcome to Doc Talk, today we're talking with pediatric neurologist Dr. Stephanie Acord. Dr. Acord sees and treats children with cerebral palsy and is a member of Cook Children’s Movement Disorders Program. She also works closely with the neurosurgery eileptology, physiatry, and stroke teams here at Cook Children’s to provide patients and their families with the most up to date information and treatment options. Welcome Dr. Acord.

00:00:27

Dr. Acord:          Thank you. Glad to be here.

00:00:31

Host:     So I'd like to start off with a little background about you how did you choose neurology and in particular movement disorders and cerebral palsy?

00:00:38

Dr. Acord:          I don't think there is actually a patient that I can recall that steered me in the direction of neurology it's more of that type of field of medicine that neurology is a lot of times people think of it more as that kind of like putting together pieces of a puzzle, and I think that's why many people actually shy away from neurology. But to me that's the challenge that is intriguing, and very interesting to me.

00:01:11

Dr. Acord:          My first exposure with movement disorders and cerebral palsy actually came here at Cook Children’s. I was in the middle of doing a child neurology rotation at the university of Kentucky and I became very interested in reached out actually to Cook Children’s and got a rotation set up here in between my second and third year of medical school.

00:01:21

Dr. Acord:          During that rotation I spent a good portion of time with doctor Warren Marks and Fernando Acosta who really showed me the ropes as maybe disorders.

00:01:31

Dr. Acord:          I think one of the unique things about Cook Children’s is that here we have several movement disorder specialist whereas many other places in the country that actually don't have any let alone several

00:01:41

Host:     Can you tell us a little about the Cerebral Palsy Program here at Cook Children’s?

00:01:48

Dr. Acord:          Cerebral Palsy clinic here at Cook Children’s is a multidisciplinary team approach in which includes the neurologist, the physiatrist, the orthopedic surgeons, neurosurgeons the therapists that are inovolved as well as the orthotics and prosthetics team. The nice thing about having a multidisciplinary team clinic is that you can have several providers looking at a patient at one particular time and all come together in terms of what do they feel like is the best treatment option for the patient that given time.

00:02:18

Dr. Acord:          And then depending on the treatment plan that's laid out is whether or not do you need to come to that clinic every time verses do they come to that clinic every so often but they don't necessarily need the resources in that clinic for every visit. 

00:02:38

Host:     So according to the CDC cerebral palsy is the most common motor disability in children about one in 323 children being diagnosed with this condition and yet it seems like there are still a lot of misperceptions around cerebral palsy even in the medical world, can you talk about what those are and why?

00:02:48

Dr. Acord:          I think that many people think that cerebral palsy is looks very similar but actually it looks very very different. Depending on the underlying etiology and severity of the injury patients can have mild symptoms to their more severe and are more wheelchair bound. About 50 percent or a little bit more than 50 percent as patients can walk independently or as about 30 percent has limited or no walking abilities.Most people kind of jump straight to the patient population with the more severe symptoms when that's the smaller percentage of the population. There's also more research that's going into cerebral palsy and early diagnosis which can also be helpful.

00:03:28

Host:     So there's also a lot of stigma associated with cerebral palsy, why is that?

00:03:33

Dr. Acord:          I think that kind of going back to what we're talking about earlier that most people feel like all cerebral palsy patients look similar, that people kind of let their minds wander to the most severe form when they hear the diagnosis. Everyone wants for their own child to have the best outcome and for them to be able to live independent lives but sometimes unfortunately that's not always the case. In some children may actually need lifelong care and diagnosis of cerebral palsy doesn't mean that it's just the child that's affected but many times it's the entire family as they're going to have to assist with care for their child sometimes lifelong.

00:04:12

Dr. Acord:          I think another stigma associated with cerebral palsy is that all patients that have cerebral palsy have intellectual disability which is not the case. It's always important you should address each patient individually because even though they may not be able to speak verbally to you doesn't necessarily mean that they're not able to understand what's going on around them. They indeed are the the center of the treatment plan and so you should always make sure that they are heavily involved in the decision making to the extent that they are able.

00:04:12

Dr. Acord:          There are many people that have normal intelligence that have cerebral palsy as well, even if they don't have normal intelligence doesn't mean that you should treat them any differently they may need assistance with daily care center activities but it's also important to still treat them as an individual. 

00:04:58

Host:     Cerebral palsy is kind of an umbrella term can you clarify what it is and what causes it?

00:05:06

Dr. Acord:          So, cerebral palsy is a group of disorders that affects a person's motor movements, posture, and or balance. It's a very heterogeneous mixture as cations in which there it is some type of injury or insult that happens in the womb, during delivery, or after delivery that the injury or insults does not itself get progressively worse with time. These are referred to as congenital ideologies and can include things such as pre maturity, low birth weight, multiple births, intraventricular hemorrhage, or IVH, perinatal stroke, cortical malformations such as polymicrogyria or pachygyria - meaning too many or too few folds - of the brain, congenital infection such as CMB or zika virus, infections acquired from the placenta or even after birth which can include hsv encephalitis, E. coli meningitis or group B. strep meningitis, birth complications leading to compromise of the placenta or oxygen to the baby such as hypoxic events or less commonly these days kernicterus. Depending on the etiology and severity of the injury will also affect the different type of cerebral palsy that have as well as the constellation of symptoms that they display.

00:06:20

Host:     So what symptoms should doctors be looking for?

00:06:24

Dr. Acord:          I think the more common signs of cerebral palsy include asymmetric use or movement of a part of the body indicating an underlying weakness. So for instance if a baby prefers to grab with just one hand compared to the other or if they're cralling for instance it’s that one leg they're dragging behind compared to the other. If they have things such as abnormal ton or posture, what we refer to as spasticity, or increased muscle tone or they can have low muscle tone which is known as hypotonia. They could also have ataxia, which is a problem with balancing and coordination, other things such as motor delay so if they didn't meet their gross motor milestones such as sitting, crawling, pulling to stand, cruising along furniture, walking, or even acquiring things such as a pincer grasp  - if they have things such as cognitive or intellectual disabilities or even if they have a strong past medical history that is concerning that they could have cerebral palsy taking a deeper look into the pregnancy history as well as the birth history can sometimes shed light into if they have signs of cerebral palsy.

00:07:33

Dr. Acord:          Many times though there's actually nothing in the history that makes this suspicious that there could have been a perinatal insult and as a result imaging can be very helpful in the situation.

00:07:44

Host:     So are there symptoms that mimic cerebral palsy or mask it? For instance, children with complex conditions, can these kids have cerebral palsy that goes undetected or undiagnosed because it's hidden by the symptoms of their other issues or appear to have cerebral palsy when in fact they don't?

00:08:01

Dr. Acord:          There can be many underlying genetic disorders that can mimic what looks like cerebral palsy as we start to learn more and more and there's more genetic testing that’s being performed I think it's helping us to identify some conditions that either may be more likely to be associated with cerebral palsy, or, the diagnosis instead of cerebral palsy. 

00:08:20 

Host:     So in May of this year the cerebral palsy foundation lowered the age of early detection from around 2 years of age to as early as 9.5 months how does this impact the diagnosis care and potentially the long term outlook for patients?

00:08:37

Dr. Acord:          I think that the earlier that you can detect these patients a better it's going to be for them in the long run. Babies that are in the NICU are starting to be identified earlier and earlier. There is some research going on across the country in which they have different scales that they're watching some of the different movements that babies have and it's allowing them to be able to determine if certain babies are at risk for developing cerebral palsy.

00:09:01

Dr. Acord:          Many times before the babies actually go home from the NICU some of them actually have been identified and or diagnosed with cerebral palsy based on what type of underlying etiology they may have or why they're actually in the NICU in the first place. The earlier that children can be diagnosed with cerebral palsy the sooner that they can actually have more hands on type of aggressive treatment options. Things that are most important at the beginning are going to be therapies but then as they get a little bit older other things such as time management can be helpful especially to help make additional progress from a developmental standpoint. 

00:09:36

Host:     So for babies who have a risk at birth, is there a time that obstetricians, primary care physicians, or neonatologists should discuss the possibility of a cerebral palsy diagnosis so that the parents of primary care doctor know what to watch for?

00:09:52

Dr. Acord:          I don't think it's so much the obstetrician but mainly more the primary care provider or the neonatologist that should be able to help to identify patients that may be at risk or that actually have cerebral palsy. The obstetricians’ information in terms of if it was a difficult delivery or what happened prior to the baby being born can be helpful but then the obstetricians usually kind of hand the baby off and then they usually kind of stay more with them on in the care for the mother. So it the baby ends up going to the NICU then depending on their reasoning for the baby going to NICU would be whether or not they need to continue to monitor and if they see any clinical symptoms that they're worried about that they need to do any type of imaging for their brain for instance, if the baby is not identified until they're a little bit older either because they have delays in their developmental milestones or maybe that there’s some weakness that they have noticed that the baby is getting a little bit older than that for their primary care provider would be able to make a referral over for those concerns. 

00:10:54

Host:     So are all cerebral palsy cases congenital or are there other injuries or illnesses that can result in cerebral palsy, maybe even among older children?

00:11:03

Dr. Acord:          Congenital cerebral palsy, meaning that something happens in the womb during delivery or after delivery, is by far more common and accounts for about 80 to 85 percent of patients that are diagnosed with cerebral palsy. There are however what we refer to as acquired cases in which that's about 15 to 20 percent of patients and that usually is consistent with patients That have had some type of traumatic brain injury such as child abuse which is referred to as non accidental trauma, it could be related to a motor vehicle accident, or it could be potentially related to some other type of fall.

00:11:37

Host:     So the child is diagnosed with cerebral palsy, what are the treatment options and how are they determined?

00:11:44

Dr. Acord:          It first depends on what type of cerebral palsy they actually have> Spastic cerebral palsy is by far the most common and accounts for about 75 to 85 percent of the different cases that we see. Depending on whether or not they are what we refer to as hemiplegic meaning one side of the body is affected and there's about 40 to 60 percent of patients that have this form. or diplegic meaning involvement of both legs is about 10 to 35 percent, or quadriplegic meaning both arms and legs are involved which account for about 25 to 30 percent. Depending on the type of cerebral palsy that they have, treatment options can look very different. There can also be things such as the dyskenetic, which means lots of abnormal movements such as involuntary ataxic meaning that if they have trouble with balance and coordination. hypotonic cerebral palsy meaning that they're kind of on the loose side or a mixed cerebral palsy which make up a much smaller percentage of the population. For pateints that we're looking at more of tone management especially from a spasticity standpoint it's always important to look at kind of the short term as well as the long term goals of the treatment plan.

00:12:54

Dr. Acord:          Many times things such as therapies are going to be one of the first lines of treatment options for these children that started a young age. And then as they start to get a little bit older things such as bracing or what we refer to as orthotics as well as equipment may be something that they need in order to achieve the particular developmental milestones. If they start having a lot of trouble with their their tones such as spasticity, then sometimes we add things such as medications that you can take by mouth which include things such as baclofen, valium, or tizanidine that get absorbed through the intestinal system.

00:13:30

Dr. Acord:          If we’re trying to do more of a focal effect for patients for instance to have diaplesia or if they had hemiplegia then things like chemo denervation with botox could be helpful to target a particular area. Moivng up to things that are more invasive, these include things such as baclofen pumps, selective dorsal rhizotomies, or even deep brain stimulation may be potential options for some of these patients depending on the underlying etiology of their cerebral palsy as well as the location and the symptoms that are associated with it. As they get a little bit older other things to consider would be orthopedic surgeries as a treatment option as well. 

00:14:10

Host:     So you mention baclofen pump and selective dorsal rhizotomy, and deep brain stimulation, can you elaborate on what these treatments are?

00:14:17

Dr. Acord:          I think we're lucky here at Cook Children’s that we have tet ability to do all of these different types of treatment options for children, the first one being baclofen pumps. Our children with more refractory spasticity that hasn't necessarily responded well to oral medications. Most of the time prior to actually implanting this device we do a trial of giving the medication like you would with a lumbar puncture and inject the medication and then have a therapist evaluate what they're tone did after the medication is on board. If they have a significant response to the medication then we usually discuss moving forward with this as an option. Sometimes baclofen pump can not only help with ease of care for patients especially if the families have difficulty with dressing or changing them but it can also help a lot with kind of pain discomfort that these patients may feel on a daily basis.

00:15:09

Dr. Acord:          Selective dorsal rhizotomy, or SDR, are pretty extensive surgical options mainly for patients who have diaplegic cerebral palsy. Most of the time these patients are selected at a younger age usually you start thinking about the process in the age of anywhere from 3 to 5 to start the workup. Usually these patients do not walk independently or they can walk independently in the home setting but when they're out in the community need more equipment to assist them. Usually we have these patients go through the surgical workup process they undergo what we refer to as a gait or motion lab analysis to really look at the dynamics of their walking pattern and see whether or not does this seem to be strictly spasticity or if they're complaining of dystonia that lays over it as well. After this the gait lab is reviewed by the neurologist as well as the orthopedist, therapist and the orthotics and prosthetics team. Usually based on this as well as it sometimes having to do a baclofen trial we usually use this information to determine if the candidate is a good candidate. If we feel like they're a good candidate in usually we send them over to you our nurse surgeon, Dr. Richard Roberts, who's performed all of our surgeries, to go through the technical piece in terms of what does it look like from a surgery standpoint as well as the complications that can be associated with it. Afterwards usually it's a pretty intensive stay on the rehabilitation unit for usually about 4 to 6 weeks and then still afterwards when they go home it's also additional therapies that must continue in the home setting. 

00:16:44

Dr. Acord:          There are also some options for patients that have increased tone in arms and legs and may not be a good candidate from the baclofen pump standpoint that could be a candidate for more of what we refer to as a palliative rhizotomy in which this is used mainly to help with daily care as well as ease the pain and discomfort

00:17:04

Dr. Acord:          Deep brain stimulation or DBS can be beneficial to patients that have more of what we refer to as dystonic or dyskinetic cerebral palsy. These patients usually have a significant amount of dystonia and sometimes this can also affect their ability to speak clearly. Dystonia can look like spasticity however they are a distinct symptom and as a result the treatment options can be different. Depending on the etiology of the cerebral palsy as well as how extensively involved the patient's symptoms are the patient may be a good candidate for this as an option. However this is a permanent implantation as a device. As a result, there's an extensive work up that goes into this process and usually with patients that have cerebral palsy that were considering deep brain stimulation usually the movement disorders team will review the case in detail and make sure that we feel like they're a good candidate before proceeding. 

00:18:02

Host:     So we know that cerebral palsy doesn't get worse over time and with treatment patients can improve even for those with the most severe forms, but what about children who don't receive intervention what happens to them? 

00:18:15

Dr. Acord:          I think it's really important to remember that the patients that do get treatments are going to do better than the patients that don't get treatments initially. Many times as the brain continues to develop as babies brains mature with age they also start having developmental patterns that occur. So for instance, if you have weakness on the left side of the body and you try to use the right side of the body because it's easier and that's what everybody would want to do then that left side doesn't get to develop those muscles and that strength like their right side does and as a result more connections and pathways are going to develop towards the stronger side leaving the weaker side appearing even more weak. Over time the connections and pathways from the brain leading down to the spinal cord and out to the arm and leg are going to decrease over time and as a result sometimes you can see some differences not only in strength but also kind of differences in how the arm or the leg looks and sometimes it actually will appear smaller not only in the length of a foot or the size of a calf but also there can be a leg length discrepancy that would have to be addressed as they get older.

00:19:26

Dr. Acord:          Things such as toe walking for instance that pattern that children develop that shouldn't usually be a heel to toe pattern if they walk on their toes because they have spasticity, then the brain starts to think that that's the normal type of pattern that should occur when they're walking and as a result if you try and correct the toe walking pattern when there are 2 or 3 for instance versus if you're trying to correct it when they're 8 it's going to be a lot more difficult when they're older to try and reverse some of those connections and pathways that have developed and to correct so many extra years as incorrect patterned walking.

00:20:04

Host:     This diagnosis has to be a real challenge for families to hear so when a family is referred to Cook Children’s how do you set expectations for outcomes in terms of care and long term outlooks?

00:20:14

Dr. Acord:          Usually when the patient comes to Cook Children’s for the first time they're usually not in the cerebral palsy clinic itself and they're usually just with the neurologist on a one on one visit. Usually at that visit I usually am pretty open and honest with the families and try and make sure that I explain to them what I'm looking for, for instance if we do any particular type of imaging of the brain or what I may be concerned about so that it's not a surprise to them when we get results back in terms of what explains the underlying cause for the symptoms. I think also laying out expectations as what does it look like right now, what are we kind of anticipating in probably the first couple of months to maybe the first couple of years and then kind of where the family is and and you got to meet them where they’re at. Some families want a lot of information up front and they're going to go to the Internet and they're going to do a lot of Googling and some types of families are only gonna listen to exactly what you have to say, and so you’ve got to figure out where the family is and how much information that they may want to know at the beginning, you also have to remember that most of the information you may tell them at the beginning they may not actually hear because once you say the word cerebral palsy they may not actually hear the information afterwards and so on subsequent visits just remembering to kind of circle back to some of the information that you had told them prior to make sure that everybody's on the same page with the treatment plan and what do we expect as they get older.

00:21:42

Host:     How is a child's treatment determined? Like who's involved in the decision making what does the care team look like? 

00:21:49

Dr. Acord:          So, depending again on the etiology of the cerebral palsy. what type of symptoms that they have, determines who all needs to be involved. Most of the time from a neurology standpoint it's going to be the neurologist that's making a bunch of different referrals and treatment plans. For instance if you have spastic cerebral palsy then depending on if it's just in the legs then they may start talking to you about things such as would oral medications be good options or more focal targeting of medication such as botulinum toxin or depending on the age of 30 a little bit older would they be a good candidate from a surgical option? And so some of these things take time in terms of planning to make sure that certain treatments they got early on aren't going to interfere with some of the results if they're going to be worked up for additional more invasive surgery such as selective dorsal rhizotomy or even baclofen pumps. But usually the neurologist is going to be the one that helps to guide the families of the different options and then whether or not they may need to go see the orthopedic doctors or they need to see the neurosurgeons and then again if they are in the cerebral palsy clinic then many times at therapist may be there as well as a orthotist could be there that can help in terms of making sure that they're getting all of the equipment that they need they're getting all the therapies that they need and they're getting the briefing that may be helpful for them.

00:23:10

Host:     How is care coordinated for these children and their families?

00:23:14

Dr. Acord:          Usually the primary care physicians are going to be the ones who are the main coordinators from a treatment standpoint. Usually the primary care providers are going to be aware of all the different subspecialists that they may be seeing as well as the comorbidities that can be associated with it. They can kind of be like their team or their home base and help to refer out to additional specialties that can assist and help with the treatment plans

00:23:41

Host:     So it sounds like the primary care physicians need to be very aware of what the comorbidities are and what kinds of comorbidities might there be?

00:23:49

Dr. Acord:          From a neurologic standpoint, the most common comorbidity in patients that have cerebral palsy is epilepsy and that accounts for about 40 percent of patients. They could also have things such as intellectual disability or autism spectrum disorder. Things that have some relevance to the neurologic system but are things that we necessarily manage would be things such as swallowing dysfunction or dysplasia. Bowel and bladder dysfunction, visual impairment, hearing loss ,or even some pain.

00:24:18

Host:     So what is the life expectancy of a cerebral palsy patient?

00:24:23

Dr. Acord:          Depending on the severity of cerebral palsy can determine whether or not it would affect our lifespan. Patients that have more severe cerebral palsy symptoms are more at risk for having a shorter life expectancy usually secondary to either the seizures themselves and difficulty with controlling them. Things such as dysphasia or respiratory problems associated with it. Patients that have the less severe forms of cerebral palsy usually have a normal life expectancy. 

00:24:52

Host:     What does the future of cerebral palsy look like? What's on the horizon?

00:24:58

Dr. Acord:          One of the up and coming fields in not only the neurology world but also the cerebral palsy world is the concept of robotics and the technologies associated with it. In the past few years the field has really started to blossom and it's allowing for a greater amount of independence for some of these patients. There are things such as wearable devices there are things that are helping with the arms as well as the legs, things like walking assistance devices as well as virtual reality equipment.

00:25:25

Dr. Acord:          The thing to remember though is that nothing can replace standard therapies. However, some of these robotic devices can be helpful to further enhance the therapy that are already in place. There's no cure for cerebral palsy however there are lots of different treatment options. I think it's important to remember that no two patients are the same and a treatment plan for each individual is different. The patient should be the center of the process as well as the family and their expectations and goals for their child whether it's to improve that patient's independence to ease their daily care, and/or to eliminate pain trying to be mindful of the patients in the family to be able to gain the best results out of the options that are available

00:26:11

Host:     Thank you so much Dr. Acord for taking time out of your schedule to talk about cerebral palsy and the treatment and care available here at Cook Children’s. The work you do is amazing and so important to the patients and families you care for.

00:26:25

Dr. Acord:          It's been a pleasure thank you so much for having me.

00:26:27

Host:     If you'd like to learn more about cerebral palsy and the Movement Disorders Program here at Cook Children's please visit Cook Children’s dot org, and thanks for listening.

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