Protecting Your Child's Health after Transplant/Transitioning to Adult Care

Presenters:  Lynda Kwon Beaupin MD, Director of Cancer Survivorship Program and Gretchen Vaughn BSN, MSN, CPNP, Johns Hopkins All Children’s Cancer and Blood Disorders Institute

This is a recording of a workshop presented at the 2019 Celebrating a Second Chance at Life Survivorship Symposium.

Presentation is 33 minutes, followed by 25 minutes Q&A.

Summary:

Survivors of a pediatric bone marrow transplant can enjoy a good quality of life long-term. However, survivors and their parents need to be aware of and monitor for late complications that can occur decades after transplant and affect their quality of life.

Highlights:

• Pediatric transplant recipients are at risk of developing health problems months or years after transplant
• Risk of late effects depends on the patient’s disease, age at time of transplant, genetic factors, type of transplant and whether the patient had graft-versus-host disease (GVHD)
• Certain chemotherapy drugs and radiation increases the risk of heart problems decades after transplant
• Pediatric transplant recipients have a high risk of developing lung problems after transplant
• Re-vaccination is important after transplant
• Beginning around age 12, children should begin learning why they take particular medications, how to make appointments, how to order prescription refills and what their health history is so they are prepared when it’s time to transition to adult care.
• Parents should ask their transplant center for a personal survivorship care plan that can be given to the child’s healthcare team, no matter where they live

Transcript of Presentation

00:00  [Vaughn] Overview of presentation: Well, good morning, everyone. We are very happy to have this opportunity to speak to you all about issues that are very near and dear to our heart, and hopefully giving you some information that can empower you to protect your child's health and help move through the remaining part of their life as they become young adults and beyond.

So, we're going to talk about a variety of topics, including what is the definition of long-term survivorship and why it is important. I want to talk a little bit about specific late effects after a stem cell transplant that could apply to your child and then resources for you and your child as they move into the adult care world.

So, as we know, stem cell transplant is a curative treatment for children who have both malignancies and non-malignant disorders. Over the past 40 years we've had many, many improvements in our supportive care, in our therapies; and therefore, we are having more survivors of pediatric stem cell transplant.

01:07  The risk of late effects, though, is unique to each individual. It depends on many different factors, including

• the original disease that the child received the transplant for
• the treatment drugs that they received to get them into a remission
• how old they were- some of the treatments affect younger children, and it'll be different if that same disease process happened to somebody who is a teenager
• genetic factors - some diseases have genetic mutations and that can give them lifelong risks for other complications that need to be unique to that child
• the type of transplant (whether they got their own cells back or whether they received an autologous transplant), and
• whether or not especially they've had graft-versus-host disease.

So, there isn't one set guideline. It needs to be very individualized and account for all of these variables.

01:59  There are at least three phases to cancer survivorship. The time from diagnosis to the end of the beginning treatment is one phase. Then when they finish therapy and go onto extended survival is the second phase but then to long-term survival. In the pediatric world, we are much more fortunate than many of our adult colleagues. We can use the word survivor. We can use the word cure, and that's defined in pediatric cancer five years from the original diagnosis and at least two years from the time that therapy has ended or post-transplant, we will use the word cure. That's why I'm a pediatric nurse.

02:37  When we think about cure, we want to think about more than just the physiologic impact of the disease and the treatment. We want to cure the whole person. So, there's a social aspect, and quality of life is very important. There are psychological aspects and effects from the therapies as well as the biologic effects on the body of the person who underwent the transplant.

Some of these topics you're going to hear in other presentation forums. Our topic today, we're going to talk about heart and lung issues, immune system issues, secondary cancers.

I think this is where I switch to Dr. Beaupin.

03:17 [Beaupin]  Impact of chemotherapy and radiation on heart health long-term:  So, as many of you that are here, and you may recall from your children's therapy, some of what we'll be talking about may be familiar to you. When we're talking about heart health risks, we are focusing on any type of chemotherapy or radiation they may have received that can affect their heart muscles.

When we think of chemotherapy, we certainly think about anthracyclines as the class of medications that we group together that we know the heart muscles are not exactly happy with when they're exposed to them. More commonly, the chemotherapy names are doxorubicin, daunorubicin and mitoxantrone, which I'd say are all readily used throughout many of the diseases that we subsequently need a stem cell transplant for.

What we've learned is that over the years, we've gotten to know the effects of these medications on the heart muscles. Really, the heart muscles, just once they're exposed, they don't like it. There can be actual muscle damage. We have electrical pathways in our heart that can actually be affected by these medications, and also, the blood vessels can be directly damaged.

When you think about radiation, you can think about different diseases that may need some radiation and where the heart may be affected. So, we look at the chest, spine, and certainly for our kids who've had stem cell transplant TBI, total body radiation, we take into account both if a child had chemotherapy and/or radiation and how old they are.

So, whenever we are assessing a stem cell transplant survivor or a pediatric cancer survivor, we're looking at different things to assess what the risk factors may be. We have learned that kids who are under the age of five when they are initially exposed to these therapies may be a risk factor.

Certainly, how much of these medications, so we call it the cumulative dose or the total dose that they received of this medication over the time of their treatment, also has an impact, and as I briefly mentioned, where did they receive their radiation. Certainly, if it's in the chest and directly in the field of the heart, that has a more direct risk versus in the abdomen or in the belly area, we call that side scatter, where even though the heart area is not targeted, there can be some radiation that can scatter towards the heart. So, we do have to take that into account.

TBI, total body radiation, as you can imagine, is the total body. So, even though that's not directly to the heart, it may certainly account for some of the radiation that the heart is exposed to there as well.

Keeping that in mind, we also know that radiation can have other effects, diabetes and cholesterol, because some of the other organs may be affected. As we know, every organ in our body is just not a single living area, but they all communicate. We'll talk a bit more about that.

06:11  Obesity, high blood pressure, diabetes, and high cholesterol increase the risk of heart problems: So whenever we talk about heart health risk factors, I think this is good for everybody to be aware of. We know that there's good evidence about being overweight and obesity having a role in increasing heart health risk. Any congenital heart disease or a heart condition that they were born with, any hypertension or blood pressure issues, diabetes, cholesterol, as you can imagine that we all know is an added heart risk factor, health risk factor.

06:37  Other issues such as smoking, drug use and diet can affect the risk of heart problems: A family history - we always like to know about as well. So, just to keep in mind that it may seem like they're unrelated to their previous condition that they needed a stem cell transplant, but that is important for us to know because we're looking at the whole person at this point. Certainly, habits such as smoking and drug use can have an effect on the heart as well.

Overall, unhealthy diet, we know of certain foods that we know help with the heart health, but we also can't exactly prescribe a diet as well. But we just know that unhealthy eating leads to the issues that are listed here.

07:18  Although the risk of heart problems is small after transplant, it can occur for decades after treatment:  So what do we look out for? I think what we need to recognize is that, though the risk is small, the risk can occur for decades after treatment. Unlike our adult counterparts, our children, we want to grow old with them. We want them to have many decades of life ahead of them. So, recognizing that it's not that five-year period after their transplant. It's not necessarily their 10-year period. But it's really for many decades after their transplant that we continue to look out for possible issues and really just even prevention of these sort of problems.

07:51  Symptoms of heart problems in pediatric transplant survivors:  So shortness of breath, fatigue, weakness, and you can see the list here. Swelling of legs and feet, and if you ever did a Google search on heart dysfunction, you'll see a lot of these symptoms listed.

For our younger kids, what is more common, that is not typically listed, is that they have more abdominal symptoms. They have more unexplained nausea and vomiting. So, I think that's something to keep in mind, and we see that more in our younger kids. Certainly, as they become more adult age, they're going to have more adult symptoms, but that is one that it doesn't necessarily come to top of mind when you're thinking of heart problems.

08:29  So, how do we monitor for these heart issues? A yearly medical checkup, the one we do like in all our survivors, and an EKG at least once when we're establishing long-term survivorship care, and the echocardiogram, which is that ultrasound of the heart that looks at heart function depends on exposure. So, you can see here whether there was ... Did they receive anthracyclines, or did they have radiation? How much cumulative dose or total dose of that medication did they receive? Did they also have radiation?

Then based on national guidelines on many survivors we've learned about in the past, we've come up with some national screening recommendations where it's either every two or five years. For some of you here, you may know that we often did every year, actually, and it was only up until fall of this year that the Children's Oncology Group came out with these guidelines because we are continually learning from our survivors and learning that do we need to do them every year, how often do we really need to do it.

It's very nice that when we get these updated guidelines and there are some changes actually, because we know that we're continually looking at this information, and what are we learning from the kids who have gone through this before, your own children perhaps. So, it's very helpful that now we can do every two or five years. So that just might be just a little change because some of you may say, "Oh, you know what? We actually get them every year." There might be some adjusting.

09:56  Pediatric transplant survivors have a high risk of developing lung problems:  The next topic is we'll talk about the lungs, the good partners of the heart here. The lung issues in a stem cell transplant can be infectious and non-infectious; and it certainly can bring you back to at the time of their transplant when the early transplant period within 100 days versus late after 100 days depends on the type of stem cell transplant, whether it was your own cells or donor cells, the degree of matching, whether there was GVHD (or graft-versus-host disease), what the conditioning regimen was and if there was recurrence of their underlying disease.

Overall, I think we need to recognize that childhood cancer survivors, so just in general, not just the stem cell transplant survivors, they have a high risk of lung issues; and it may not be so apparent during their treatment. For stem cell transplant survivors, the intensity of their transplanted-related therapy and their previous therapies, as you can imagine, add to their overall risk.

For this group of kids, you're thinking of did they get TBI, how much TBI did they receive, what chemotherapy agents did they receive prior to their transplant or as part of their preparative regimen, and did they also receive lung radiation.

11:11  BOOP - bronchiolitis obliterans organizing pneumonia:  Some of you may be familiar with BOOP. It is a condition that is unique that we see in donor stem cell transplant patients, bronchiolitis obliterans organizing pneumonia. It's a very, I'm sure Gretchen can speak to this, a very challenging condition.

We can't really say why this happens, who is at more risk and what triggered it. It could be a viral infection that triggers it. You can speak to this more. It could be kids that had a very high risk of pulmonary risk exposure or medications previously, but it can be chronic, it can be irreversible; and it can cause a lot of symptoms.

The severity can really range from person to person, and it's unpredictable, I'd say, and I imagine very challenging to treat, as Gretchen sees a lot of our long-term survivors from transplant. The symptoms can also vary. They can be very severe or very just chronically there, but mild, more mild, to put it mildly. It could be a chronic cough with or without fever, shortness of breath, so you're thinking of that for different conditions, and breathlessness with activity is something to keep that in mind.

12:28  So how do we monitor for these lung problems? Again, we can't stress enough that even a once-a-year visit with someone who is familiar with your child's cancer history and stem cell transplant history or even if it was for a non-malignancy, that history is important.

A pulmonary function test at one year, it's that breathing test that you do where it looks like you're in this Star Trek tube, and you have to do these breathing commands, and they do different tests on your lungs with that. They are usually done at one-year post-transplant or once age appropriate, because usually it's kids who are the age of six or above that can really be able to do this test. I've seen them. I think it'd be hard for me to do what they're asking me to do, so I can only imagine a young kid who has to kind of do these deep breathing and deep breathing and quick breathing out and all that.

So, if they are unable to or there are clinical concerns, we do discuss with the lung specialist as to how can we test for some of the concerns here, and we really use their guidance. Again, lifestyle modification, we really do ask that they avoid tobacco use and exposure. I'm going to now switch back to Gretchen, where she'll cover the immune system and secondary cancers.

13:43  [Vaughn] So, just to add one comment to what Lynda was saying, when I see the long-term survivor patients, I ask such questions as, "Do you have a cough? Do you have shortness of breath?" Or another screen question is, "Can your child play and run equally to their peers?"

Because if they are trying to be active and getting short of breath, then that's a red flag to me that maybe I need to look at their lung function a little bit more closely. It's just a simple question; and it's that annual visit that gives me the opportunity to pose the question that can help us to protect your child's health.

14:15  Immune system recovery after transplant:  So immune system recovery is near and dear to my heart. People think, "Oh, you've had your transplant. You're good." At six months we start to evaluate the immune system, but that's only because we want to get the baseline. We're not expecting it to be normal then. We look again at nine months and again at 12 months.

Depending on the type of transplant that your child had, the type of treatment that they had, it's going to be impacted by the preparative chemotherapy, if they got drugs such as antithymocyte globulin - ATG, it impairs the T lymphocytes - if they needed the drug called Campath (that's a more broad immune suppressant), if they got graft-versus-host disease and they have needed long-term steroids or tacrolimus- all of those things work by depressing the immune system. So those patients are going to take even more time to have good immune system recovery.

Broadly, in the kids overall, it's the neutrophil that's all-important. Your neutrophil is important because it gives you bacterial protection. But in the immunology world, we think about the T-cells, which I've had described to me as the conductor of the immune system, telling it when to turn on and turn off. We monitor T-cell function by a test of mitogen, where we stimulate the child's blood against different kinds of stimulants, and we measure how much their T-cells can react to that. That gives us then a percentage of normal, and we can measure recovery.

Besides the T-cells, we have to look at the B-cells, because those make immunoglobulins in your body, and those immunoglobulins, IgA, IgM and IgG, are important for vaccination responses and memory long-term immunity. So those are all the components that we have to look at.

Generally, T-cells recover more quickly than B-cells, and B-cells respond to signals from the T-cells. So, you have to have both parts working well to have a complete immune reconstitution.

16:11  Vaccination after transplant is important:  So we think about vaccination. Prior to many years ago when I was newer in this field, we thought, "Oh, just the children who got a transplant from an alternative donor need to be revaccinated because the auto kids, they don't get quite as much chemo, and we don't have to worry about them. Literature and evidence based over time shows it's important that both those children who got an autologous transplant as well as those who go an allo transplant need to be revaccinated.

So, we test their immune response, their memory to vaccinations, at six months, and we can see that it's been wiped away. Then we give the vaccinations, and then we follow to make sure that they are in fact making the appropriate responses. For these kids, we only give the killed vaccinations first, and then when we can document that those have been safely responded to, then usually starting only two years, do we recommend that the live vaccines be given. Those are your measles, mumps, rubella and your varicella vaccine.

So, it's like the baby shots. If you think about the vaccinations, we need to start from ground zero, so they need the diphtheria/tetanus, polio, the Hib vaccine. There are two types of pneumococcal vaccines. The pneumococcus, the PCV 13, has been determined to be the one that gives us the strongest immune response, so we want your child to have three doses of the PCV 13. The PPSV is the polysaccharide. It's a different form [inaudible 00:17:43] pneumococcus, but it has a longer-range benefit. So, they need to get three of the PCV 13s. Then the first one is Prevnar; the second one is Pneumovax. But they need to be in that order. Then they need to be vaccinated with meningococcus as well, starting with a quadrivalent form of that vaccine.

So, beyond kind of the baby vaccinations, it's the other vaccinations that are also important - hepatitis A and B. We are learning that the human papillomavirus is important to protect your child against because secondary cancers can happen for our patients who are unvaccinated. I've seen the commercials on TV. "Well, your parent didn't know that you could get this vaccine." It makes my skin crawl. Yes, parents do know, or many people do know. But it is an important vaccination post-transplant as well. That's the comment that I made already about the live vaccines.

The varicella vaccination is one that we look at responses to: it's the only one of the original ones that your child has received that for which sometimes you can maintain that immune response. That's because this virus lives in your nerve roots, and if it starts to activate a little bit, your immune system can even respond later. So, that's the single one that we may not have to revaccinate against; but we will check a titer to see which category, your child needs it or doesn't need it, they fall into.

19:13  Secondary cancers:  Then I think one of the scariest and saddest things that can happen after transplant in my mind is what happens because our treatment damages rapidly-dividing cells: a secondary cancer can be a consequence of some of the curative therapy that we needed to give your child to start with. So, I want to talk about that in just a few minutes as well.

Thankfully, overall the risk tends to be very low. We know from research and from experience that it's isolated, in general, to some of the specific chemotherapy agents that raise the risk for a secondary cancer. So, as a group, they're called alkylating agents, but sadly, these are some of the same drugs that we need to use as preparative regimen.

The cyclophosphamide, also known as cytoxan, busulfan melphalan and etoposide, these drug,s in particular, are associated with an increased risk of leukemia over time. Radiation therapy, because it damages all cells in the body, can give rise to a secondary cancer. So, it depends on, again, the dose and the site of the body that was irradiated.

In particular, skin cancers are a risk factor. Women or young girls who got chest radiation therapy have an increased risk against those didn't about developing a breast cancer. Then colon cancer is an increased risk if there was radiation to the abdomen. So, we need to think about that as we monitor your child over time.

So, what we're going to do, we've said it once, we've said it probably five times, every single year please, you need to have an annual physical exam. Some of those can be coordinated with your primary care doctor if those people are informed about also what to watch for.

21:02  Dental screening is important. In particular, patients who got a transplant for Fanconi anemia, because they have a chromosomal fragility, are at increased risk for cancers in the mouth or squamous cell carcinomas. If somebody is symptomatic, we don't need a CBC every year for the next 50 years. But if you have symptoms, then blood work could help us early pick up a sign of a developing leukemia.

21:28  Certainly, MRI and mammograms are important as screening and prevention for young girls and young women starting at an earlier age than the general population guidelines might otherwise recommend. Then colon cancer screening, again, if you've had that abdominal radiation. Again, at earlier ages than in the general population. So, now, Dr. Beaupin is going to talk about transitioning to adult care.

21:59  Transitioning children to adult care: [Beaupin] So, I think this is a very exciting portion when we think about survivorship. I think it all depends on where we all live in the country and, also what our kids are doing when they become young adults and where they move off to. Because I have three young ones, and I can never imagine the day that they are out of my house, but I guess that happens.

22:20  So, when do we transition them? I'd like to keep them forever, and certain centers do, but that all depends, right? It all depends on your insurance coverage, where you live, where the young adult, adults now live, wherever they may live, nationally or internationally, and multi-disciplinary care is what we're interested in, right?

We pay so much attention to the physical effects of anything that we use to treat our underlying condition, and yet we also recognize that it's not just an MD or a nurse practitioner or physician assistant that is needed here. We actually need to call on other specialists, as you can imagine. So, where will they receive this care, and who will be familiar with the potential risks that we've so far reviewed?

Also, communication. We certainly want to do a handoff as seamlessly as we can. I think communication is probably the key to everything in our personal lives and, as you can imagine, in anything that we do work wise, politically. It's all about communication. So, even here for us as we transition kids to adult care, it's very important.

23:36  What are we looking for, and what should the survivor be aware of when we are transitioning care et al? It's really about when did they receive their transplant and what was their original diagnosis and when did this all occur. I think that's very important. How far out are we talking here? What was the original surgery, chemotherapy, drugs and total doses of specific ones that have some impact long-term?

Radiation treatment and the doses, what part of their body they radiated, and how much radiation did they receive? Importantly, the new birthdate that we always talk about, their transplant date, and really what was their preparative regimen. That is all such important information on this one slide that really needs to be conveyed to any physician, I think, that comes into their care in the future.

Were there complications? Again, I look to Gretchen because I'm sure, and many of you may be familiar with the long-term complications that they may have had as a result of their transplant. Graft-versus-host disease can be an acute issue; but obviously if it's a chronic one, that has a lot of implications in addition to what we've added here. Infectious complications, such as even the BOOP, is that something that exists, and was there an infectious component that led to it? As we've mentioned, the history and the treatment is all important here.

25:09  Really, I think the question comes up is when do kids become more engaged and involved with these visits. We certainly, I think all of us, we're all at Johns Hopkins All Children's Hospital. We've seen kids at different ages, right? A 12-year-old, you can have 10 12-year-olds in front of us, and each one can be different.

But really that tween age is a good time to start incorporating them into our visits and really engaging them when we're talking about their medical issues and why we're talking about the things we're talking to. That's also a good time when they can start having a journal, themselves, about their symptoms, what they're worried about maybe, or they have questions about.

They should really start being able to explain their own medications that they take or if they have any problems and spend one-on-one time with their provider. We, as providers, I think we do try to do that once they reach this age, to spend some individual time with them and also, then, engage also the parents as well in that visit before we finish the visit out.

26:15  They can start calling to make their appointments and certainly request their refills. I think that's something, as parents, we should try to encourage them to do, even if we're with them, so that they become more comfortable being part of the visit, actually being proactive. Request supply, yeah, I was going to say, I did this, reminding to set alarms because I think kids, more and more kids, are having their own phones, and that could be a whole talk in itself. But I think we should empower them to use it for more than just YouTubing, and they can use a lot. That phone is very ... They can do a lot of things with this thing, and it's making appointments and reminders and all that that we should do.

So, it's really, can't say it enough, the reason why we want to engage them is because they are going to be on their own eventually. They are going to transition to an adult person. I always joke. I'm 43, and if I was diagnosed with cancer and I had a transplant, my parents would still be coming with me.

I was in Buffalo previously, and our survivorship program did cross into the adulthood range, and we had people older than me whose parents still came with them to their annual survivorship visit. So, definitely, knowledge is power. They need to understand what's going on here, but we recognize that this is a family experience as well.

27:41  So, each year, we do want to assess their knowledge on their issues as it relates to their late effect risk and their survivorship care plan. For instance, they should know why we do their blood pressure and why that is important. I'm sure every center has their own health history forms, but they really are the ones who need to start filling it out.

Also, the family history, I think they blindly, and we see this, we see kids who are in their 20s who are unfortunately faced with a condition, and their parents are still filling in a lot of the family history stuff and all that. But I think we need to take a pause and recognize that they are totally capable of understanding this information and what that means.

28:27  Where can young adult transplant survivors find good care?  So, even before we go into that, I was going to say I think the question comes up is where can we seek care. I had a slide where, even if you Google pediatric survivorship care center, you will get a whole host of places that have, not only a pediatric survivorship center, but you can then specifically look at a BMT survivorship center, and they are dotting along the whole entire country. So, that no matter where your survivor goes, where they go to college or where they end up permanently, or if the whole family moves, sharing records and transitioning that care is something that is very doable.

Many people go back to their original center. As kids come back for annual visits or anything like that or even during holiday time, we can always accommodate that. But please know that these centers, they exist everywhere, and as you can tell, it's a concerted effort. We all work together. These national guidelines are what they are, so that any pediatric stem cell transplant survivor can go to any center, and the same guidelines would apply. I think that's what's really nice.

29:39  Some of you may have a passport for care account through your survivorship center. Maybe not. I can tell. We can talk more about that. But, actually, it's a program that many centers have that is in partnership with the Children's Oncology Group, and it lists a treatment summary as well as a care plan and lists all the risks and what the surveillance regimen or schedule that is recommended.

So, for things like Gretchen mentioned, like breast cancer risk and doing a mammogram and a MRI screening for a young woman, it's listed as to when to do that and certainly for the colon cancer as well.

30:20  Be The Match has transplant specific personalized care plans:  [Vaughn] I'm going to just interject here because I went to the session that happened before this one with Dr. Linda Burns, and the National Marrow Donor Program has a bone marrow transplant specific, personalized care plan. They have brochures at the booths here, specifically right now for six and 12 months.

She also talked about an app that is available that can be used on your electronic device. So, my bone of contention is there's a lot that's been done for the oncology population, but if your child had something like a storage disease or an immune deficiency, or sickle cell, or thalassemia, there's less about that. So, the information that I heard from the NMDP site, they have it that applies to non-oncology patient survivors as well.

31:07  Pediatric cancer survivorship centers do see patients with non-cancer diagnoses as well:  I do urge, and that's a good point, because I think even the kids who did not have a cancer diagnosis initially, these pediatric cancer survivor centers typically do see all those kids as well, and they all should have a treatment summary and a care plan for them as well.

So, that is a struggle. I think a lot of families don't know which resources or services are available to them if their kids did not have a malignancy per se but an underlying condition that needed a stem cell transplant, but please know that you can always reach out to a pediatric cancer survivorship center program, and they will help you guide you. I feel pretty confident about that.

They also mentioned that there are 140 adult transplant centers around the country. In the room at that previous session, there were probably 50 people. One adult had a survivorship plan. So, if you feel like your child doesn't have anything, you're not in the minority. But we're working to make that better.

We can actually ask even here and ask who has that.

32:11  Summary: So, in summary, I think we need to recognize, and I think this, above all, is that many children who receive a stem cell transplant lead healthy lives. That is our goal, and by healthy we mean not just physically but overall have a very good quality of life and live very fulfilled lives.

Treatment received for their cancer or other original disease and their preparative regimen for stem cell transplant, as you can see, have long and late-term effects.

Survivorship centers exist for children and adults all throughout the country and internationally; and really that transition to adult care should not be complicated. We all need to do a better job of working together with the adult centers and be able to find you someone to continue care with, whether it's going to an adult center or whether you move to another place or anything in between.

Question and Answer Period

33:05  We are now going to have a question and answer part of our session. I will request that if you have a question, that you will ask it in the microphone because we are audio recording this for those who couldn't be here. I'm going to get the other mic, and then Rachael is going to walk it around.

33:24  Can we ask in this group, though, who has had a treatment summary or a survivorship care plan for their children, that they're aware of?

33:35  Sounds like there's a need.

33:39  Okay. If you have a question, please raise your hand, and Rachael will come around.

33:49  Question about risks of radiation to specific area versus total body irradiation:  The factors that you listed were for total body radiation, the areas treated or chest or certain areas. Is there a different more likely to have certain types of recurrence or issues that someone should have for total body radiation versus specific chest area?

The second question is a lot of the presentations have talked about total amount of dosage of radiation and chemo. Is that something that, as a patient, you should be concerned about in talking with your doctor? If we're doing the regimen of all of the preventative maintenance, or if we're doing that actively, is that enough? Should we be looking at the total amount of chemicals and radiation that is received and discussing that with our doctor?

34:35  [Beaupin] I think that the total doses are very important because somebody that had a malignancy and relapsed twice before they came to transplant is going to have a different history.

In the transplant world, we also historically had myeloablative conditioning regimens for most every disease, and now you may hear reduced intensity conditioning regimens. So, as we've learned about the side effects and we've learned that some diseases can be safely transplanted with lower doses of different agents, we're moving in that direction. But I would say that it's important to know where the

Certainly, if you've had something like a lymphoma and you've had chest radiation, the thyroid is important; the heart is important; the lung is important. Young children, bone growth is impaired; fertility is impaired. If you've had brain involved in the radiation, learning deficits, hormonal endocrine issues.

So, we talked about just the heart and lungs today, but knowing where the radiation was, and how much it was and how old the child was is going to give your provider the information to know to look at those other areas of the body and those other diseases and conditions and late effects, more than just the couple that we've talked on this topic because the other presenters are presenting on those other subjects. Does that answer your question?

35:54  [Vaughn] Partly? I was going answer to your first one as well because I think your question brings up a lot of good points that can be shared here, especially seeing that there are no hands that came up for a treatment summary and a care plan. Because we've talked about that and we say that, but you might not exactly know what we're talking about. So, where you received radiation and what areas and total dose, I think your first question asked, do we know if that correlates with an increased risk of ...

So, absolutely it does. It depends on what type of radiation you received because there are now different types of radiation that one can receive. Over the years it has become much more targeted so that we can focus specifically on the area that needs the treatment and decrease the side scatter that I had mentioned before. But it all kind of depends on when the radiation received was and what type of radiation because some of them were not available, depending on when the radiation was given.

So, yes, it does have some application, which then leads to the treatment summary. When we talk about that, your provider, whether it's your stem cell transplant team or your oncologist, probably one of the two. If you had an underlying non-malignant condition, they probably are not the ones who could help you most, but certainly the ones that were involved with your stem cell transplant care. Someone will be able to get records and be able to look at what the treatment was and be able to summarize all that.

37:25  So, when we provide a treatment summary for all of our kids, typically they are cancer kids who've completed treatment, we actually go through all their records and list all their chemotherapy medications. Not for all of them, but for the pertinent ones, we will list what the cumulative dose was because that does have implications as to what the risk is of developing a heart condition, an infertility risk- those are couple that I can name. The amount of radiation, and that can lend to risk of a secondary

So, I urge you to get that. Some of you might be surprised. Some of your children's records may actually have that. Sometimes I've had patients where we've given them out, and parents don't recall having received it. That certainly happens because we just give so much stuff. It's just so much stuff, so it could be in there. We always have record of it, so you should be able to ask for it at any time.

To give a good idea, we had a child who was very young, a non-transplant but just to give an example, that Mindy and I saw in our survivorship clinic. He had a type of Hodgkin lymphoma that actually just needed surgery, but they thought he had radiation so they came and received the treatment summary. He was about 12 years old, and we actually advised that he come again when he's 16, 17 so that he knew. Because if you walk around thinking that you are a cancer survivor, you may think you have all these risks, and you may or may not.

So, this document, I think, is very important for parents to have. But as their kids get older, they should have it and understand what it is, and we're always happy to review it. So, what goes along with this treatment summary that summarizes all these medications is actually a care plan, a survivorship care plan, that actually, taking into account what your treatment is, specifically lists what the risks are pertinent to the treatment summary.

They're actually very clear because we've learned so much over the past several decades of these cancer survivors, that if you had this much radiation in this area, you should get surveillance for your skin, for an echocardiogram. I'm probably missing other things, but yeah, a lot of things. Sorry. So, anyways, I urge you to get your treatment summary and your care plan.

39:49 [audience] So, when do you recommend screening for secondary cancers in the pediatric population? I know they give us some dates for the adult population, but I'm wondering if that changes for kids that received a transplant at a younger age.

40:04  [Vaughn] We do that at our annual visit all the time. So, historically and honestly, until these new guidelines came, you can imagine sometimes that we were doing once-a-year blood count to check for leukemia. That's a good example, right, because that's kind of one we're looking for.

I think what we've learned from these survivors, it's not that once-a-year blood test that tells us any ... That's not what really found a lot of these secondary cancers. It really was symptoms. So, I think it's important to know that you have these risks and to know if there are these symptoms and what to look out for, and you bring it to someone's attention.

Because at our annual visit, if we do a once-a-year CBC, a complete blood count, that might be totally normal, but that doesn't give you reassurance for the whole year. But I think what we've recognized is that we're maybe doing these blood tests just to do them, but they're not giving us any reassurance. Maybe we should be looking at the whole person and are you having symptoms.

40:56  [audience] What about mammograms?

40:58  [Vaughn] So, that depends on what condition you had. If you had radiation, it's something to put you at risk, and there are actually guidelines to say that you should get them 15 years after your exposure to radiation or at the age of 25, whichever one comes later. So, if you were five years old and needed chest irradiation, if we calculate that, that would be the age of 20, or it should be the age of 30 because it's whatever comes later. So, there are guidelines specific like that. Did I say 25? It should be 25, yes. 20, 15, that was a bad age to use as an example.

41:37  I think the skin cancer risk is something that is really critical at every visit, and using appropriate sunscreen cannot be overstated, both to prevent chronic graft-versus-host disease but also melanoma of the skin, which can be a very serious secondary cancer. The ounce of prevention is worth a ton of cure. So, your skin is your largest body organ. You need to protect your skin.

I have to say about the breast, it's eight years or 25, whichever comes later. Sorry for the confusion. Skin cancer is actually the most common cancer that we see. Usually it's the non-melanoma, so we have to look at everything every year. But things to know. But yeah, so they're serious. So, every year we like to kind of look at the whole picture and see where we have to target our exam or our questions to.

42:28 [audience]  So, where can we actually get the care plan?

42:32 [Vaughn] The National Marrow Donor Program, they have a booth out here. They have the six-month and 12-month guidelines for questions and symptoms. On their website, by the end of the summer, they were just telling me at that other session, they will have something that you can go online and download, and then it can be individualized.

But certainly, speak to your transplant center and say, "Even without the official plan, give me the summary. Give me the details. Give me the information. Give me the doses. Give me the ages. Give me the diagnosis. Give me the molecular information." All of those things, we have it, and you can ask for it, and we will give it to you. Then wherever you take your child, if you have it with you, then the provider on the other end can evaluate that and can consider what they need to do to help your child stay safe.

43:20  [audience] Because we go to All Children's. We see you sometimes. So, we could just go there and ask for the care plan, and then you could give it to us?

43:29  [Vaughn] We could do a treatment summary. We are getting more in tune with the need to provide them, so I apologize that we haven't had it available in the past. But we're working in that direction.

We should preface that because a lot of the efforts have been in cancer survivors and not yet in our pediatric transplant survivors. So, we actually are now going forward providing this for our-

So, even many of our oncology kids have not received a treatment summary because definitely moving forward it's now part of the standard, but a lot of centers, to catch up on the kids that we haven't. But it is something that, so for the next visit and everything, we should be working on.

44:12  [audience] One more thing. Because our son, he was diagnosed with leukemia, and he ended up having a transplant, a bone marrow transplant, and then recently, because you're talking about the secondary cancer, he had this melanoma. I don't why. Maybe because of the radiation because he had total body radiation, and a lot of moles starts appearing. Yeah, so much, like all over his body, from his head to his toes, at the tip of his finger. Then we had some of it checked recently, and one of them came out like a melanoma, and several is kind of like a pre-melanoma, and the childhood melanoma is kind of like that.

44:58  [Vaughn] So, that certainly is a risk and probably because, as you mentioned, he did have TBI? Or he did not?

45:04  So, total, yeah.

45:04  He did, yes? Total body radiation?

45:06  He did.

That's why I say that when we transition to other providers, it needs to be multidisciplinary because sometimes the dermatologist is important to include in the evaluation and the recommendations. Sometimes it may be a pulmonologist. Sometimes we have to involve the cardiology team. So, when we look at long-term late effects and thinking about the whole child, we need to think about all the other disease specialists that can help to know, to monitor and to prevent or to then treat any complications that arise.

45:42  [audience] I guess that's it. But they removed the melanoma. They did a biopsy again, and they said that they were able to remove all the cells around it. So, there's no further treatment needed for that.

45:55  [Vaughn] But certainly continued monitoring is still going to be important.

46:04  [audience] So, we're pretty new. We're just about six months post-transplant, so we haven't hit that one-year mark. But just so I have in my head, because I did talk to our bone marrow transplant team about something like this, and they weren't sure exactly how to put it together, but then I did get something.

So, at a year, is it right then that I'll know when we go and start this, that it will be an exam, but what will be taken into consideration really are the skin, the lungs, the heart? Those are the key players, and then we kind of monitor the stomach all the time. But the key ones, and at that time is it just looked at and evaluated and then determined if a dermatologist is necessary? Because we do have a lot of freckles. So, is the one-year mark kind of the time?

47:07  [Vaughn] That's the time that we do really the most extensive initial evaluation, but we're looking at kidneys. We're looking at your renal function test in the blood. We're looking at urinalysis for any protein. We're looking at high blood pressure. We're looking at symptoms of cough or breathing problems. We're looking at growth and height and weight. So, what seems like just a routine physical gives us a lot of data about your child's progress and things that need a second look. As well as then the immune system and the vaccination and your body's responses and all of those things.

47:42  [Beaupin] Tell me if I'm wrong, Gretchen, but I think the one-year mark is obviously a very significant mark in transplant but also what has been going on. So, what is the infection status? What is the GVHD status and all that? It takes into account at that one year to see, because I think everyone will be a little different. I'd say even much more individualized for transplant population than even a general oncology kid. So, all that takes into consideration. But freckles, for instance, you should kind of know what the baseline is, and we would include and refer to a dermatologist there with something that we felt was, and you helped us, that was more suspicious or concerning.

I've been to presentations by other transplant center experts where they take pictures on an annual basis, and they keep them. For chronic graft-versus-host disease, the symptoms may be minor in the beginning, but if you have photographs of your child's skin or they actually stripped their patients down to just their underwear and took front and back pictures and put it in their medical record so that that could be monitored over time, I think those are important pieces of data.

Well, those are the kinds of things, those are extra special little tricks that, as a parent, when you go in and you don't know a whole lot, those are the kinds of things where, if you're not sure if your doctor or your team is doing it, how do I find that kind of information? To know if our facility is doing that kind of thing, because that's a great thing. The pictures are a great thing. I think everybody should do that, but you're saying some do; some don't. How do I find those other tricks of the trade? I guess talking to other parents.

And just knowing your child's history. If your child never got total body radiation, if your child is darker complexion, if your child never had chronic graft-versus-host disease, those screening elements vary in their critical importance by all these other underlying factors.

So, I don't know that. But anything that's different to you, anything that's a concern, anything that you don't know, if you can look at the ages that they got and the risks that are associated with those drugs, then that gives you the clue as a parent what your team should be assessing for as well.

I think a good question is ask your team, "Do you have a survivorship clinic or program here?" Right? Because sometimes with BMT there are so many complications and things that they're looking out for that's BMT directed, but many transplant centers will have a survivorship center.