Late Effects after a Pediatric Transplant/Transitioning to Adult Care

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Late Effects after a Pediatric Transplant/Transitioning to Adult Care

Saturday, April 17, 2021

Presenter: Robert Hayashi MD, Professor of Pediatrics in the Division of Pediatric Hematology/Oncology, St. Louis Children's Hospital, Washington University School of Medicine

Presentation is 43 minutes long with 11 minutes of Q & A.

Summary: A pediatric bone marrow transplant can cure a child’s disease, but it can also create a number of physical, emotional and financial issues that need to be addressed, even when the child becomes an adult.  This presentation discusses common challenges children face after transplant, and strategies to provide them with a good quality of life long-term.

Highlights:

• A bone marrow, stem cell or cord blood transplant can cause health problems for survivors, even decades after transplant.  
• A survivorship plan that details a child’s past treatments, drugs and therapies received during transplant, and tests that need to be done life-long after transplant is important to optimize the child’s long-term health and happiness.
• Survivors of a childhood transplant may experience emotional and intellectual difficulties as they grow older, which can impact educational and employment options. Planning early to help a child secure a good job and health insurance is important.

Key Points:

(01:11)  Over 3,000 bone marrow transplants are performed each year for children who have a blood disorder.

(02:22) A bone marrow transplant can disrupt a child’s physical, emotional and intellectual growth.  

(08:46) Predicting possible late effects must take into account the effect of prior therapies as well the bone marrow transplant

(10:04) Thyroid disease is a common late effect after transplant.  

(12:18) Long-term use of steroids after transplant can weaken bones and alter the blood supply to joints.  

(14:39) Radiation, chemotherapy and/or brain injury during a bone marrow transplant may affect a child’s intellectual development and school performance., which may not be evident until years after transplant.

(18:58) Transplant may make a child infertile. Sperm banking or egg harvesting may enable patients to have children in the future.

(22:06) Sexual development is different from fertility. If a child is not advancing through puberty normally, early intervention with hormone supplementation may help

(24:33) Transplant can change physical appearance and body image, which can impact emotional health.

(27:30) A detailed summary of all treatments before, during and after transplant is important for a child to have and to give to all physicians who care for the patient for the rest of his/her life

Transcript of Presentation

(00:00) [Sachit Patel]  Introduction. Hi, everyone. This is Dr. Sachit Patel. I'm the Director of Pediatric Transplant at the University of Nebraska Medical Center, and Children's Hospital and Medical Center. I welcome all of you on this Saturday to a wonderful session entitled Late Effects of Pediatric Transplants, Transitioning Pediatrics to Adult Care. I'd like to introduce a wonderful physician in St. Louis by the name of Dr. Robert Hayashi.

(00:28) Dr. Hayashi is a professor of pediatrics in the division of Pediatric Hematology Oncology at Washington University School of Medicine, and an attending physician at St. Louis Children's Hospital in St. Louis, Missouri. He is also the director of the Late Effects Clinics at St. Louis Children's Hospital. His research focuses primarily on the long term effects of cancer therapy, and he is involved in regional and national efforts to better understand the late effects with the goal of developing interventions that will improve the outlook for this patient population. Please join us in welcoming Dr. Hayashi.

(01:11) [Robert Hayashi]  Over 3,000 bone marrow transplants are performed each year for children who have a blood disorder. Thank you, Dr. Patel. I would like to take this opportunity to thank the organizers of this symposium and for the invitation to speak today. And hopefully, I'll be able to provide you with information that will be useful for all of you.

(01:31) So hematopoietic stem cell transplant or bone marrow transplant as you all know, is increasing in its use in this country, and there are now probably over 3,000 procedures [in pediatric patients] performed in this country per year, and that is expected to grow with time. Transplants were originally used to treat cancer, for instance, leukemia, lymphoma or solid tumors like neuroblastoma, but with advancing technologies it is now feasible to utilize this modality to virtually cure any primary disease of the blood, and that includes immunodeficiencies, sickle cell anemia, metabolic diseases like Hurler's disease. So we expect that more and more patients will utilize this technology.

(02:22) A bone marrow transplant can disrupt a child’s physical, emotional and intellectual growth.  As pediatric patients who are undergoing this procedure, they're obviously expected to not only be cured of their underlying condition, but they're also expected to live many years well into adulthood after the transplant procedure. And during this time, we expect these children to grow substantially as they move into adulthood. They will obviously grow in size, their organs and bones will also grow, but not only the physical, but their intellect will also grow as they advance in terms of their intellectual function advancing through their educational process. The transplant procedure, however, can interfere with the normal growth of any of these aspects. And so it's important to have an appreciation of exactly how this can potentially impact a patient so that we can best manage their situation.

(03:20) Overview of talk. So, this is a summary of the topics I hope to cover today. We're going to talk about some basic principles so that we can get our arms around exactly how to think about a child who's undergone a transplant procedure as we look toward the future. I'll provide some specific examples which may be relevant to some of you out there who have undergone a transplant procedure. But just to kind of give you a sense of the scope, but also the complexity in how we approach the management of these patients, which can be very different depending upon what kind of problem we're talking about. I will emphasize the importance of something that's called a treatment summary, and the necessity of having one that you build throughout your lifetime.

(04:08) I will specifically address issues as it relates to monitoring growth, because again, as children, we expect these children to grow, and we need to monitor all aspects of growth to provide the best possible care for our patients. And then finally, the ultimate goal is to help a child ultimately achieve a state of independence where they're fully grown adults, they're well-integrated in society and can continue to meet the challenges that they face independently if needed.

(04:48) Our understanding late effects after a pediatric is evolving. Patients need to stay on top of the latest research to ensure they are getting proper care as they get older. So, starting at the beginning, just want to kind of get some definitions clarified. We define late effects very broadly. It's really any long term difficulty experienced by a child from the transplant procedure. This can be physical or damage to a specific organ. This can be intellectual as I mentioned, and obviously this can affect school performance, but it also can be emotional. We can have children experience difficulties either from the transplant procedure or from some of the late effects they experience. And irrespective of what the nature of the late effects is, if it's impacting the child, it's important and it needs to be addressed seriously.

(05:38) The other point to make about late effects is that the research in this area is relatively new. We needed to have successful transplant procedures and we needed time to pass by before we could actually see the effects of transplantation on children as they grew many years and moved into adulthood. And so, this is really a field that continues to grow, it continues to evolve. We clinicians and researchers continue to learn new things every day. And so for a patient or a family member, it's really important to stay current because things you may have learned years ago may not be relevant today or maybe approached totally different and it's important to provide the best care possible by keeping up-to-date with what is going on.

(06:36) Chemotherapy, radiation, and drugs given to fight infection or graft-versus-host disease can cause late effects after transplant.. Every component of the transplant can have an effect. So obviously chemotherapy, particularly with transplant procedures and their intensity, can cause a variety of effects on the child. Radiation not surprisingly, can have long lasting effects on a child, but also some of the medications that we use to support the children in transplantation. Steroids can have their effects. Some of the immunosuppressing agents such as tacrolimus or cyclosporine, beyond just affecting their ability to fight infections, they can cause long term injury, and that has to be managed.

(07:22) Damage to organs or bones that patients had prior to transplant, or developed during transplant, may persist after transplant. Any illness through the transplant course can obviously sustain itself over time. If a child got a serious infection during the transplant procedure or had something affect their liver, like veno-occlusive disease, some of those things may persist as persistent problems well after the transplant procedure has passed. And then, the transplant procedure is not a perfect technology. There are some aspects of diseases that children may have that may continue irrespective of whether the transplant procedure was successful or not. Examples are children with Hurler's disease who may continue to have bone problems, problems with their back, patients with adrenoleukodystrophy who may have had permanent damage to their adrenal glands and will have continued adrenal insufficiency long after the transplant procedure. And then patients who had received previous treatment for their condition like, for instance, cancer patients who receive treatment prior to the transplant procedure. Those treatments in and of themselves may have caused problems, and obviously need to be taken into account if you're going to provide a total picture in terms of the management of the patient.

(08:46) Predicting possible late effects must take into account the effect of prior therapies as well the bone marrow transplant. So, obviously, the way I've summarized these things it's very clear that the management of the transplant after the transplant can be very complicated. Some parts of the transplant procedure may have what we call additive effects or kind of ganging up on specific organs or conditions and make the problem worse. For instance, radiation can have effects on the heart as well as chemotherapy. And so those things can maybe add together in very unpredictable ways. And so, we need to really take all the information we have, both regarding past treatments leading up to the transplant, the transplant procedure, any treatments that were provided after the transplant procedure to really provide a total picture, to provide the most comprehensive management of patients moving forward.

(09:41) So let me give you a few specific examples just giving you a sense of the nature of problems that some patients may have. And some of you who may have undergone a transplant procedure may have either experienced something like this or may be undergoing evaluations for this. But this is really to hopefully give you have a better sense of the nature and scope of the problems that we're talking about.

(10:04) Thyroid disease is a common late effect after transplant.  So, a very common late effect is thyroid disease. So the thyroid is an organ that sits in the middle of your neck and its primary function is to regulate the energy of the body. Radiation, if you received radiation as part of your transplant procedure, that can cause some level of damage, but it can also alter the genes of that thyroid and potentially cause cancer. So there's potentially two problems with it, with the thyroid either being damaged or becoming a cancer with time.

(10:41) The organ can swell and get big, that's called a goiter, and it may lose its function. And so some of the signs that your thyroid may not be working well is that you seem to be more fatigued or sleeping all the time, your hair may be thinning, you may be retaining weight or getting puffy in funny ways that are kind of difficult to explain. And unfortunately, like many late effects, thyroid disease can often take years to develop. And so it can sneak on very gradually, you may not notice it coming and then all of a sudden you have these symptoms, and it's a consequence of this. And obviously, some of these symptoms are not obvious in terms of how you put this together in terms of one condition.

(11:27) Patients at risk of developing thyroid disease should have a thyroid function test annually for the rest of their life. So, to manage patients who are at risk for thyroid disease they really need to have tests of their thyroid function, which is a blood test, and that should be done yearly for all intents and purposes for the rest of the person's life because the thyroid can fail at any point in time, even 10, 15, 20 years later. And the other important element is that the thyroid needs to be examined by a care provider who's familiar with knowing what a normal thyroid looks like, what it feels like, how to detect nodules or bumps that may be cancer cells so that we can address those conditions as quickly as possible. So this is just an example of how we approach a condition like thyroid disease.

(12:18) Long-term use of steroids after transplant can weaken bones  and alter the blood supply to joints.  Another scope of late effects can be manifested by patients who've received steroids. And because steroids are a very important part of graft-versus-host disease, many patients who've undergone transplantation have been exposed to steroids. And probably most of you are familiar with some of the common side effects of steroids. They can cause diabetes, they can make you put on a lot of weight, they can give you persistently high blood pressure. But over time, particularly if you have to stay on steroids therapy for a long period of time for, let's say, graft-versus-host disease, this can have a long term and potentially permanent impact on the bones. This can make them thin, not as strong, and that can lead to chronic breaks, which obviously cannot just alter your function but can be a source of pain.

(13:11) Periodic bone density tests can detect bone problems after transplant. They [steroids] can also alter the blood supply to joints and cause failures of the hip joints or virtually any joint in the body. And some of those problems may require surgery, like hip replacements, in order to fix those things. And so in order to really manage the bone problems, which is one of the most pressing issues for steroids and long term effects, you need to stay on top of how the bone health is, and that's usually done by bone density tests, which can be done in most hospitals and can give you a sense of whether your bones are weakening.

(13:53) Exercise and getting a sufficient amount of calcium and vitamin D each day can strengthen bones. Things that you can do to maintain your [bone] health are to obviously take calcium and make sure that you're getting a good source of vitamin D because that will help put calcium back into the bones and make the bones stronger. And exercise is a very important part of management in terms of patients who are exposed to steroids. You want to keep your weight down so you don't put undue stress on your joints, but also as you exercise you actually promote calcium buildup in your bones that makes them stronger, particularly if you're doing resistance exercises like mild weightlifting or things like that. So that's very important to keep in mind.

(14:39) Radiation, chemotherapy and/or brain injury during a bone marrow transplant may affect a child’s intellectual development and school performance, and may not be evident until years after transplant. Moving on to something totally different is school performance. Many children can have difficulties with their school work after transplant, and that can be a product of many things that can affect intellectual development. The radiation can have effects on the brain as well as the chemotherapy. Past cancer therapies could have effects as well. And also, if a patient experienced some complication of the transplant that lead to potentially injury to the brain, like having seizures or strokes, that will further build on potential things that will impact a child's development.

(15:24) So children will often show these problems by not doing well in school, particularly not performing as well as they had when they were prior to the transplant procedure. And as they advance through grades, the work gets harder and their struggles with school may be even getting worse with time. And so you can have a child who may be doing well in early grades, but as they are challenged to do more difficult things, then they may have failing grades when they'd never had problems with grades before. It's very hard for us to predict how a child is going to do until they're challenged intellectually. So for instance, if you're in first grade, you're not going to know whether you're going to have difficulties with calculus in the future until you reach high school or college and take calculus and realize that the transplant had that specific effect on your brain that made it a more difficult area of study than perhaps others.

(16:34) Neuropsychological testing is recommended to detect and manage these problems early. So the only way we can really get a handle on what an individual child's problem may entail is by doing what is called neuropsychological testing. And so, this basically is a process in which all aspects of a child's intellectual function is assessed. They can be very long tests, sometimes it can take several hours. They also test memory which is very important. You may see some children after the transplant not have as good a memory for things as they used to. And so we use this tool so that we can get a good profile of the difficulties a child may be experiencing, and then we can assist families in terms of ensuring that they get the services to accommodate those particular weaknesses. Most states mandate this by law. And so if you have documentation that a child's having difficulties in school as reflected in their neuropsychological testing, the neuropsychologist will provide specific recommendations to allow the child to maximize their school performance, and schools are in general obligated to fulfill those responsibilities.

(17:54) And so, we encourage families to do neuropsychological testing early and typically we often repeat it about every three years. It's better not to wait until problems develop because they can be more difficult to manage, but most importantly, it's very important that a clear profile is identified before a child grows up and advances into college. Because many times if you haven't established that there are problems earlier in their educational process and already have implemented services, sometimes colleges will not be as accommodating with the lack of documentation and the necessity, demonstrated in the early school years that the child needs. So any child who is at risk for intellectual difficulties, we would encourage neuropsychological testing into something that make it a regular part of their evaluation.

(18:58) Transplant may make a child infertile. Sperm banking or egg harvesting may enable patients to have children in the future. Another area that's very important to patients and families is fertility. The transplant procedures have different effects on fertility. And you may be familiar that there are transplant procedures that are called myeloablative procedures, and typically those are often associated with high rates of infertility. Or you may have other children who may undergo what are called non-myeloablative procedures and so then there's a greater potential to have children once they reach adulthood. And so, it's very difficult to specifically quantitate a particular child's fertility risk even if you know exactly how they were treated. And so, we make specific recommendations for children and families who are being evaluated for a transplantation even prior to the procedure. It's best to have these discussions, an undergoing a plan to perhaps have backups to preserve fertility. Sperm banking is readily available for many families as well as egg harvesting. And having those secured prior to the transplant procedure at least ensures that you have options to have children in the future irrespective of what happens during the transplant.

(20:30) After the transplant, it's still important to assess a patient's fertility potential. You shouldn't necessarily be fatalistic and say there's no chance of having children, it's important to get evaluations, get opinions, and perhaps undergo testing like sperm counts or what's called an AMH level which gives you a sense of how the ovaries are working. And then if, in fact, there is the potential to have sustained fertility, we recommend serious consideration of doing something early, because oftentimes over time, over the years, that person's fertility can decline with age. And so you may not have the same fertility potential when you're ready to have children than perhaps you did earlier more immediately after the transplant procedure. And so these are the kind of discussions that we encourage families and patients to have because we don't want them to wait too long and the opportunity is lost.

(21:35) Fertility preservation may not be covered by insurance, but other financial assistance may be available. These resources are often not covered by insurance companies. Although some insurance companies do so, cost becomes an issue. There are resources that are available that can assist with providing financial assistance, and those discussions are obviously important to ensure that you have every opportunity available to maintain the ability to have children in the future.

(22:06) Sexual development is different from fertility. Sexual development is different from just fertility, it really pertains to how a child advances through puberty and how they maintain their sexual function. There're actually different parts of the ovaries and testes that are responsible for sexual development versus fertility. So it's conceivable that you can have a loss in fertility and have normal puberty or at least much more sustained puberty. So you shouldn't make assumptions of one versus the other depending upon whether you're having difficulties with either fertility or puberty.

(22:49) If a child is not advancing through puberty normally, early intervention with hormone supplementation may help. Experienced providers will know that if a patient's not advancing through puberty that that's obviously a red flag. And so obviously, you need to maintain normal follow up with either your pediatrician or your physician who's overseeing the late effects of your child to make sure that they're advancing along the normal pace that you would expect for a child advancing through puberty if they received their transplant procedure at an early age, because there are certain interventions that can be implemented if we see that the child is having problems, and many of those are hormone supplementations. But oftentimes, there are certain windows in which to gain the full benefit of these treatments you need to recognize them relatively early. So it's something that should be a regular part of normal medical management, so that efforts can be made to make the situation as easy as possible.

(24:01) And further on, some children or young adult transplant survivors may lose that function. They may go into early menopause or experience low testosterone. And hormone supplementation in those settings are also very important. And so just like thyroid disease, this is something that needs to be followed indefinitely for a patient so that we can provide appropriate services when and if a patient's having difficulty.

(24:33) Transplant may cause changes physical appearance, body image, which can impact emotional health. Emotional health, as I had mentioned before, is just as important as any difficulties that you may be having with a particular organ that got impacted by the transplant procedure. As many of you know, the transplant procedure has the potential to alter aspects of a person's physical appearance. Some patients end up shorter than they were projected to be. Some patients who may have graft-versus-host disease may undergo permanent skin changes that persist. Some patients may have chronic hair loss that doesn't grow back. So body image has the potential of creating a significant burden on the patient, and it's not surprising that over time that can actually significantly impact a person's emotional health. Particularly in a growing child in school, particularly as they advance in their teenage years, peer acceptance can potentially become a challenge.

(25:45) Counseling may be appropriate for healthy emotional development. And not just from the physical appearance, but also the emotional development. Many survivors tell me that you their perspective on life having experienced the potential life-threatening condition is very different than the average young child or adolescent who may have a more carefree approach because they haven't had the same life experiences. And that asynchrony in terms of emotions perspective can make it difficult to develop strong relationships, have normal friendships, et cetera. And so it's not unusual for patients to need some assistance and counseling to try to get through some of these hurdles.

(26:36) Persistent physical limitations and chronic pain can affect emotional health. And then there can be persistent physical limitations, and particularly chronic pain. If you're experiencing chronic pain either from a damaged joint or something else, that can obviously impact your emotional health, and oftentimes that requires assistance. I think probably the most important thing is to acknowledge the fact that these things can happen, that there are things that are really not a child's fault, that it was a consequence of the therapy, so that you can move forward to find solutions and provide therapies that can make a child have a more healthy future moving forward.

(27:30) A detailed summary of all treatments before, during and after transplant is important for a child to have and to give to all physicians who care for the patient for the rest of his/her life. So, having given all those examples, I want to stress the importance of what we refer to as the treatment summary. So the treatment summary is a record of all the complex medical information on a patient's history. And that's not just the transplant procedure, but any pre-existing therapy, any pre-existing health problems. But central elements to a treatment summary is obviously the underlying diagnosis that a child received the transplant procedure for. Any complications of the therapy, specifically listing organs that may have been impacted by the transplant procedure or infections that may have caused the problem. Any surgeries are very important. The dates of the surgeries, the nature of the surgeries, even the name of the surgeons are often important. So you can go back and retrieve records and that's very important.

(28:25) The details of the transplant procedure are very important, knowing what the nature of the chemotherapy radiation were, what kind of stem cell source, was it a cord blood, a peripheral blood stem cell, an autologous transplant? And the immunosuppression, all those things are extremely important. And this is something that you would maintain as a life record. This is something that you would build upon. It's a permanent part of you, and as you move forward and experience new things, you want to add to refine it so that we have a current picture of a patient's condition. And that assists all healthcare providers to provide the best information as possible. Particularly if you change doctors or if you've moved to another location, having a robust treatment summary can make all the difference in the world in terms of providing strong, continuous healthcare for a patient.

(29:26) So again, what should be in the treatment summary? They should have all of the late effects that... Well, let me just rephrase it. So, clinicians who manage patients with late effects can use the treatment summary to assist a patient and family to maintain their wellness. And so, not only are the details of past treatments important, but also by taking that information, by taking the current testing, we can then generate a profile of what issues are relevant to you. So, if you think about the potential side effects the patient may have, it's a huge laundry list that could take up hundreds of pages. But an individual often will manifest only a handful of problems, and to be able to take that historic information and then make it relevant to you or your child's condition into very discrete problems that have been documented and established for your child just makes it easier for both you and your clinicians to navigate through these problems.

(30:36) And then a ideal treatment summary also has an educational component. Once we identify that there are specific problems, we want to be able to provide you information in terms of how you think about these problems. And so there'll be phrases like if you have a heart disease, or let's say you've received a medicine called adriamycin, which is often actually not used for transplant but it can cause damage on the heart. So you can say, because you had adriamycin you are at risk for heart disease. And then that would follow with discussions to saying, as a consequence, you should be monitored by X. It may be echocardiograms, it may be blood tests, but there would be specific recommendations. So knowing what your particular risk factors are, we can then outline specific things that should be part of your routine management.

(31:33) A treatment summary should detail warning signs of problems and encourage preventive measures to maintain health and protect the body. And then for you as a patient or a family member, we want to make it more simple. We want to say, these are the signs that you should look for, and if you see these signs, you should alert your clinician that you are experiencing these things and this may be a sign that your heart's not functioning well, or your thyroid is not functioning well. And so those are things that we know what those signs are, and we can provide information for you to assist you.

(32:00) And then finally, we want you to play an active role in terms of protecting your own body. So there are things you can do to prevent yourself from experiencing significant health problems even if a particular organ may be at risk. So again, with the example of heart disease, meaning maintaining good weight, controlling your blood pressure, regular exercise program, controlling your lipid profile, those would be things that would be specific for a person who's at risk for heart disease. And obviously, depending upon what your particular profile looks like, those scope of recommendations would be different. But this is what an ideal treatment summary would have, it would have the historic information, it would have the documentation of the specific problems that you're experiencing, and then an educational component with each specific problem providing you with information to how to maintain your wellness as best as possible.

(33:00) So the treatment summary can be invaluable as a tool to keep you or your child healthy. And so you should view it as such, it's your property and it's something that you should keep updated, you should keep multiple copies so that you have them in safe places. And obviously, anytime that you have to go to a doctor, you should bring it with you, if they don't have a copy, so that they can put it in their chart and also educate themselves in terms of what kind of problems you have.

(33:32) The treatment summary will be especially helpful for doctors unfamiliar with pediatric transplant late effects. And the recommendations that we have at least on our treatment summaries are very helpful, particularly for clinicians who may be inexperienced in late effects. So you may go to a... Move to an area in which you may not have a robust late effects program. So the treatment summary can supplement any limitations that you may have in your own healthcare network, so that they can at least see these are the things that the clinician should be doing or assisting you with to maintain wellness. And so that becomes a really important aspect. And it's just another reflection of how much you as a patient or a family member need to invest in yourself, be confident in what you know, and to be able to advocate for your own wellness.

(34:27) Transplant can affect how a child grows and organs develop. Problems may not be evident until decades after transplant. Last couple topics. Monitoring growth. Children grow and they undergo many changes. And when they receive a transplant procedure, the growth may not go as planned, depending upon how the transplant procedure affects them.

And so the youngest children are most susceptible. So obviously infants are more susceptible than school-aged children who are more susceptible than old people because they have to overcome the challenges and grow normally, and that's a big demand for the body to overcome, particularly if they've been impacted by the transplant procedure.

So, the organs grow, and so sometimes they may do fine for a while but suddenly show signs of failure maybe decades later after a child's procedure.

And so that's important. We talked about intellectual growth and emotional growth. And so, as a child advances through each stage of development, they're going to be new challenges. And it'd be great to say that this is the scope of problems and it's never going to get any worse with that, but unfortunately, in a child it's going to evolve, and problems that were initially big problems may go away, but new problems will develop. And that's just part of being a growing child, and we should accept that and meet that challenge so that we can provide the best care possible for these children.

(36:02) Regular screening tests will help maintain good health. So what is important in terms of maintaining good health? Regular screening tests are important. We can't tell in particular whether someone's having a problem unless we do what are called screening tests, which are very simple tests often in the clinic, just to see if there are early signs that there are difficulties. And so we put a lot of emphasis in trying to make this as convenient for families as possible, but screening tests are very important.

(36:31) When a problem is identified after transplant, it is important to address it immediately so that it doesn’t get worse. And once you have a screen test that shows an abnormality, it's extremely important that you follow through and get the more formal testing and any interventions that's necessary. Putting off late effects only further hurts your child because of the growing issues. They need to maintain their wellness, maintain optimal function of all their organs as they grow. Or if you don't intervene at the earliest point, the child's just going to fall further and further behind, and that makes the challenge more difficult as you move forward. Don't wait for the problems to become obvious, a child may develop severe illness from some of these late effects, but then the management becomes more urgent, it may be harder to get access to services, and sometimes opportunities may close.

(37:26) So for instance, if a child is fully advanced in puberty and it's realized that the child has growth hormone deficiency, the bones are already mature and the child will not be able to grow any further even if they get growth hormone supplementation. However, if you catch it early, recognize it early, and implement it before the child's bones are fully matured, you have that potential to catch up.

(37:52) We talked about failing in class and the difficulties that can occur.

(37:57) And again, just like I had mentioned infertility, trying to capitalize on opportunities to preserve fertility is important to address early because you may not have the flexibility or the opportunity to capitalize those as you move forward.

(38:12) A successful transplant is wonderful for a child, but that’s not the end of the story. Many challenges lie ahead. At the end of the day, the goal is to achieve independence. And this goal encompasses many things. It means optimizing your health, it means optimizing your happiness. It's very important that you address the long standing emotional strains. We realize a successful transplant is a wonderful thing, but it's not the end of the story. And it's unfortunate that many challenges may lie in the future, but we have to accept that as part of the process that we experience, and we have to commit ourselves to not walk away from this process and do everything possible to maintain our health.

(39:01) Side effects of transplant may limit a child’s long-term employment options. Optimization of education. There are many patients who may have specific problems because of a specific late effect. They may not be able to do anything they want to as a long term career. And so, if you have a chronic back problem, working on a factory line may not be an optimal situation. Or if you have vision problems, you may not be able to drive or do something that allows you to do those kinds of things. So it's important that you're honest with yourself, you take the steps to identify your late effects and let that mold your career goals. There are many opportunities out there to have a fulfilling life, integrating the late effects that you have, so that you aren't struggling advancing yourself into adulthood.

(39:53) Pediatric transplant survivors will need a need stable job and health insurance in adulthood, to cover their unique healthcare needs. And that's some of the things that we put a lot of emphasis on, particularly as the children get older is to say "We know you have these problems, you can be happy and successful if you move in this direction, and we're going to help you do that." Because at the end of the day, you need to have a stable career and job. And it's not just because of being able to maintain a certain lifestyle, but a stable job typically reflects stable insurance. You're going to have an increasing number of health difficulties as you get older, you need to be insured so that that doesn't become an impediment for you to be able to move forward. And so our goal is for you to be happy, healthy, and insured. And if we achieve those three goals then we've done our job.

(40:43) It is good to develop a plan, with the child’s cooperation, on how health and work challenges will be managed in adulthood. It's never too early to start developing a strategy. You set out a plan that invariably will be need to tweaked as things evolve. The patient needs to be an active participant, particularly as they get older and they can understand their problems. We have to have a plan that they can embrace that they can accept that they're going to commit to. And so, just telling people what they have to do without their buy-in is not a very effective strategy. And this is a lifelong commitment. And so early preparation, so this becomes second nature for a growing child is really the best strategy so that acceptance of that plan can be done.

(41:25) And so oftentimes, it's important for a growing child to accept more responsibility, to become more familiar with the problems that they're experiencing, And as they get old or mature, play a more active role in terms of not just decision making, but specific active steps that they do to promote their wellness. And adherence, this is all about maintaining adherence through life. And if we have adherence through life to a commitment to wellness, we'll have a very successful outcome.

(41:58) Summary of presentation. So, in summary, pediatric survivors of hematopoietic stem cell transplant can have diverse long -erm problems with varying severity, impacts physical, intellectual, and emotional states. Treatment summaries are very important in terms of providing information for both clinicians and patient families. And families need to stay engaged with late effects clinicians to stay up-to-date with what's going on, but also stay in touch with how to improve their lives as they move forward. Again, I want to thank the organizers of this symposium for having this opportunity, and I'd be happy to answer any questions that you might have.

Question & Answer Session

(42:47) [Sachit Patel]   Hu, this is Dr. Patel again, and I just want to thank Dr. Hayashi. That was a wonderful summary and overview of a very broad topic. You could take each one of those slides and do a whole lecture in itself on the various issues. So wonderful job summarizing.

(43:04) We do have a couple really good questions and that sort of underpin some of the things you've talked about. So I'll go ahead and ask the first one that's in the chat box. And if there's any additional questions, please include them in the comment box or in the chat box, please.

(43:24)  So the first question is, "Who can help my son..." And this individual states her son is 14 years old, and two and a half years post-transplant, and who can help manage her son's yearly follow ups? It seems as if he has had no GVHD and is doing really well. But it sounds like this mother is asking how does one orchestrate this? Because it seems that this mother in particular is doing it on what seems to be on her own. So how can she better help coordinate her child's global care?

(44:04) [Robert Hayashi]      Yeah, that unfortunately is a challenge. I think, depending upon where you live and how different programs are structured, there can be potentially several avenues. Sometimes if you had a history of cancer, you may return to your primary oncologist and that oncologist may be able to provide the coordination and support for late effects. Other programs have very specific late effects clinics. We actually have a clinic specifically for transplant patients, and so those are obviously more aligned in terms of providing those information. But at the end of the day, you're going to need to provide a strategy that you know works for you.

(44:55) So being informed as possible for knowing what needs to be done. And if you can't find someone to fulfill that role, it may lie on you to do that. And that's an unfortunate answer, but that's often a common one. Particularly if you move from region to region across the country, you'll find pretty substantial differences in terms of what services are offered, so that's why this whole process of the treatment summary and maintaining advocacy for yourself and your child is very important.

(45:35) [Sachit Patel]  Yes, I would echo those sentiments myself. It's tough depending on where you are. And but I would say to this mother as well is that she's doing the absolute right thing in engaging in conferences like this to find more information and advocate for her son, and see who the regional experts are, and continue to reach out to experts and other venues to see if there's a long term survivorship in your area. Oftentimes, and I won't speak for Dr. Hayashi, but I imagine his wonderful clinic does this as well, is that referrals can be made and they can provide that initial summary and send you back to your local doctors with a comprehensive plan. And so yeah, please continue to reach out.

(46:32) The second question in the chat box is from an individual with a wonderful email address of Led Zeppelin. So unfortunately, I want to ask more questions about that, but I can't. But his question is, he says, "Hello, I'm a 25 year old post-BMT patient with AML. Do you think it's still good for me to have a treatment summary or to make that treatment summary now given how far I am after transplant, and that I don't have all the specific details of what I received at that time, but do you think it's still a good idea to seek out a summary and have that available?"

(47:14) [Robert Hayashi]    I certainly feel that if you can assemble a treatment summary to the best that you can, and if your providers can help you, that's still even at this stage an invaluable tool. Even things like knowing that you had radiation or did not have radiation or if you received Cytoxan or not, can be very important things even if you don't know the specifics that puts you in a category where we can kind of assemble different risk factors that would be specific to you. As you've seen the BMT InfoNet has resources to kind of help you with that.

(47:57) And I may get in trouble for this, but I belong to an organization, on the board of an organization called the National Children's Cancer Society who has in their website, Beyond the Cure. And you can type in your own profile to the extent that you know it and it will generate some information that will be relevant to you in the fashion of this treatment summary that I articulate. So there are resources out there with many organizations. It may require more homework from you and more efforts, but to the extent that you can engage with your past providers and get some information or just try to assemble it from your memory, something is better than nothing. And it actually, even if it's a small amount of information, it's still pretty valuable.

(48:48) [Sachit Patel]      Wonderful. There's no more additional questions in the chat, but I do have one for myself as if I'm allowed as the moderator to ask your expertise is, is that a couple questions and that in summary would be, where do you feel we have the most knowledge base in terms of our late effects outcomes? Perhaps where do you think we have the least knowledge? And that kind of goes with where the least knowledge is. What do you think we as a community need to work on in getting better answers for our patients? And what sort of late effects outcome do you feel like we're continuing to struggle and we need to be better at?

(49:34) [Robert Hayashi]      Well, I would say there are some areas in which have been known and obvious for a long time like thyroid disease, [inaudible 00:49:42] malignancies, in which we know we have a lot of information and we have a pretty good sense of what's going on. I will say that even some of the conditions that we've known for many, many years, let's say conditions of the heart, we really don't have a good handle in terms of what that really entails, because although there's been a lot of work studying patients or children who've undergone transplants, there has been, it's much more difficult to do research on adults who had transplants as children. The patients often move, they have like this one person had indicated may not have access to their records, and so there's still a lot of unknowns.

(50:30) I will say one of the biggest challenges that we experience and it's really kind of on the forefront of our particular interest is trying to get the childhood cancer survivor to engage and take ownership of their health. It's very easy, particularly if you consider that an adult childhood transplant survivor maybe 19 or 20, the average 19 or 20 year old has a very carefree view of the world and often isn't likely to kind of immerse themselves in some of the complexities that it often takes with regard to survivorship management.

(51:14) So we try to make the picture simple, but we also try to our best to get the patients and families to engage in that the time is now to do things to keep the patient as healthy as possible. And that's a struggle for us. I mean, people don't want to consume themselves after succeeding a transplant procedure and to embarking on yet another journey. And so that has been a big focus of our work.

(51:44) [Sachit Patel]      Thank you. Thank you. An additional question just popped up. We do have certainly some time to answer more questions, and so the additional question is, "I am 20 years old and 10 years post-transplant. I was wondering what adult secondary cancer screening should I be receiving now and in the coming years?"

(52:07) [Robert Hayashi]  So there are recommendations through this organization and other organizations like the Children's Oncology Group, et cetera, that provide cancer screenings. The comment I would make is that there are two things to consider. Number one is the time since the transplant. So as you get further out from transplant, conditions become less of a concern. So most leukemias caused by transplants usually occur within the first five years. A lot of the sarcomas for patients who've received radiation occur in the next for 10 years after a transplant. But as you move into adulthood, your risk for cancer still persists.

(52:50) And we're now appreciating now that it's your elevated risk for adult cancers compared to the general population that appears to be a problem. So things like colon cancer, melanoma, breast cancer, are things that children don't experience, but childhood survivors of transplant procedures do. And so those recommendations continue to evolve. They are available on a variety of websites, and you should have discussions with your provider, particularly someone who's familiar with this topic so that they can best serve you well.

(53:34) [Sachit Patel]  Closing. Thank you. So with that, we're nearing the end of this session. And so, just a brief conclusion. On behalf of myself, BMT InfoNet and all the partners, we want to thank you, Dr. Hayashi for taking time on your Saturday afternoon to give us this wonderful summary. Great remarks, great answers to your questions, and your guidance and expertise is certainly valuable. I know our patients and the patients that are on this truly benefit from your comments. So for those who are online, please click on the left, or excuse me, please click on the link on the left on your screen and you can view the other workshops taking place this afternoon. And I encourage you to join them and learn the most you can from this wonderful symposium. So thank you again, Dr. Hayashi, and all those who attended.

(54:28) [Robert Hayashi]      Thank you.