After Transplant: Finding Qualified Health Care Providers

Transcript of Presentation:  

(00:01): Sue Stewart:  Introduction. Hello, welcome to the workshop After Transplant: Finding Qualified Healthcare Providers. My name is Sue Stewart and I'll be your moderator for this workshop.

(00:13): It's my pleasure to introduce today's speaker Dr. Paul Carpenter. Dr. Carpenter leads research and clinical care teams that support bone marrow and stem cell transplant survivors long after they finish their initial treatment at the Fred Hutchinson Cancer Center in Seattle, Washington. As director of the world-class post-transplant adult clinical care long-term follow-up program. Dr. Carpenter and his colleagues help transplant survivors and their primary care physicians manage post-treatment complications as the patients recover and resume their lives. Please join me in welcoming Dr. Carpenter.

(00:56): Dr. Carpenter:  Overview of Talk. Thanks Sue for that very kind introduction. It's a pleasure to be with you from Seattle.

(01:09): So my topic selected was How do you find a qualified healthcare provider after transplant? To answer that question, you have to understand what survivorship really means. When does it begin? What are the care models, and what is their feasibility? And then, what are the goals of long-term follow-up care after transplant?

(01:31): And I'm going to show you my approach, which I call "Core to the Outer Spheres" for comprehensive long-term follow-up (LTFU). I'll talk about survivorship care plans, which many of you have probably heard a little about, and then end with what makes the ideal long-term follow-up health care provider.

(01:55): Long-term follow-up care begins around 100 days post-transplant. So when does long-term follow begin? It begins with this red part of the arrow, Phase Four. Really at around about a hundred days post-transplant is when we in Seattle typically send patients back to their referring oncologists or hematologists. It is a little earlier in the setting of autologous transplants, where these patients get very high-dose chemotherapy and their own cells back. So that may happen sooner.

(02:24):  And then just to remind you, when we talk about true long-term follow-up survivors, typically in the literature they talk about at least two years from transplant. But these earlier phases you're familiar with. You may be diagnosed at a town where there isn't a transplant center. So from that point you're referred to Phase Two for a transplant consult, usually at a transplant center, and then you undergo pre-transplant workup at that transplant center and ultimately undergo in Phase Three, the high-dose chemotherapy and/or radiation therapy. And you get your early post-transplant care often as an inpatient in the hospital.

(03:06): Long-term follow-up care is important because transplant patients are much more likely to have post-transplant health conditions than the general population. So why is long-term follow-up so important? So regarding BMT survivors, there'll be at least half a million of them estimated in the US by 2030. And about two in three of these survivors will have at least one healthcare condition, which we've learned is about double the rate in their siblings. So early detection and prevention is a focus, because we aim to prevent significant complications and premature mortality associated with those health conditions.

(03:36): So this study, which is getting a little old now, published in 2010 that reported on the life expectancy of patients treated in Seattle who had survived at least five years. So, quite a long way out from transplant. And among the 8,000 or so transplants done through the year 2002, pretty much all of them had high-dose conditioning. The bulk of them had passed within five years, relapsed, had a second transplant, or were lost to follow-up.

(04:08): This left about 2,600 greater than five-year survivors who, about half, were aged 46 years at the time of the analysis. And you can see the age range, 6 years up to 80 years, and half of them were 13 years post-transplant. And the longest one out at that time was about 36 years. So if you were a five-year survivor, about 80% then survived 20 years post-transplant.

(04:31): So what we learned from this study with those constraints was that life expectancy was lower for the older transplant recipients versus the pediatric ones shown on the top curve here. And overall, the mortality rates were several-fold higher than the expected population rate.

(04:52): Transplant survivors may have a shorter life expectancy. Now on the right, what does that translate into in real terms? If you're 20 years of age at the time of transplant, then your estimated reduction in life expectancy years is in the order of 17 years. Versus if you attained age 60 after transplant, your estimated life expectancy reduction is about seven years. But that's about 30% lower than the general population in general. So that was the snapshot back more than 10 years ago.

(05:30): A more recent study and this was a collaborative study led by Smita Bhatia, looked at life expectancy and how it's improved for survivors. In this case, the survivors were those who had survived at least two years post-transplant, and how it's improved over the last 40 years. But what you'll see in the data is that this was more obvious in the pediatric survivors. So this was about 5,000 patients transplanted at these institutions between the mid-seventies and 2014. So 12 years longer than the other study I showed you.

(06:03): Across the three time periods, what differed from the previous study was that older patients received transplants. And that's because the conditioning for transplant became less intense, therefore more tolerable. However, there was more chronic GVHD in this period as time went on. And half of these transplant survivors were 12 years post-transplant at the time of analysis.

(06:25): So on the left you've got the pediatric patients and on the right you've got all patients. First thing to note is that in year 2000 people transplanted between 2005 to 2014, shown by the upper curves, did the best. So there has been improvement over time. But the improvement was more noticeable in the pediatric patients shown by the separation of these curves.

(06:48): And what I just wanted to draw your attention to here is that for the pediatric patients, there was an overall 8.5% reduction in life expectancy, right? So much less than what I showed you on that previous study. Not 30%, 8.5%, and that translated to about two years of life. If you take all comers, and this is mainly driven by the adult patients, the overall reduction was about 20% in life expectancy or 8.7 years. Again, lower than the 30% from the previous study.

(07:19): Now you can't compare them exactly, but remember this study has less intense conditioning, more older patients being transplanted, and then what's important here in the bottom is that 20% can be split up or seen as 21%. If you had no chronic graft-versus-host disease, the life expectancy reduction was less. It's not too dissimilar from the pediatric patients over here. But if you did have chronic GVHD, your life expectancy was more impacted.

(07:53): Long-term transplant survivors have higher rates of second cancers, cardiovascular disease and lung disease than the general population. Now, if you survived through 30 years post-transplant, the leading causes of death were relapse and infection. Note how much greater this is: 52 times higher than the general population. Second cancers were about five times higher than general population. Cardiovascular disease and lung disease are all higher than the general population. And so this speaks to the things that we need to focus on in long-term follow-up.

(08:20): Despite post-transplant issues, survival rates for long-term transplant patients are improving. The good news is that this is a Seattle analysis of about 3000 patients, a contemporary analysis going from patients transplanted between 2005 and 2019. And you can see by this middle curve as the purple dots that our chronic GVHD rates have declined from in the 50% range down to about 27% for all comers. And at the same time, relapse rates have not increased, which one might predict if chronic GVHD rates went down. And survival, shown by the gray line, is continuing to improve for our long-term follow-up survivors. And just as an aside, in children, this chronic GVHD rate is now at about 10% or less.

(09:09): Many aspects of transplant treatment can put patients at risk for later complications. So why is long-term follow-up so important beyond survival? You've got these pre-transplant exposures, conditioning, chemotherapy, radiation. You've got other chemotherapy or radiation given for the malignancy before they got to transplant, and then you've got the disease indication for transplant.

(09:30): Premature discontinuation of long-term follow-up care can put patients at risk for late effects that are not detected or treated. And then on the right. post-transplant. you've got exposures of graft-versus-host disease, infections, medication toxicities. All of these impact organ function. And layered on top of that are the underlying patient genetics, age, gender, and lifestyle. And all of these effects, even if the patient's looking good, let's just say they don't have any graft-specific disease and they got through transplant with none of those major complications, the late effects of all of these blue boxes may not show up until about seven to 20 years after transplant.

(10:03): That's called latency, and that's super important as a segue to this next slide, which is a huge Japanese study of transplant survivors -18,000 patients almost. One of the key problems is premature discontinuation of long-term follow-up. So this red dot shows that 10 years after transplant, about 28% of patients have prematurely discontinued long-term follow-up. And by 25 years, that's about two-thirds of them.

(10:30): Maintaining-term follow-up care is especially important for younger transplant patients. So when I'm counseling my patients and this is particularly true of my adolescent and young adult patients, I make them aware of that concept of latency, which just because you look good doesn't mean you should skip your long-term follow-up. And unfortunately this is a problem.

(10:46): One of the reasons that fell out of this Japanese study is that the doctor often instigated premature discontinuation of long-term follow-up based on the patient's good condition or physical condition. Something like, "Well, you don't need to see me anymore, you look great." And the most likely at-risk from this study were the adolescents and young adults, but also transplants done for non-malignant diseases. Aplastic anemia would be one example. Another example would be what we call standard-risk rather than high-risk malignancies. And certainly those patients without chronic GVHD often prompt discontinuation, premature discontinuation of long-term follow-up.

(11:30): So long-term follow-up differs after whether you've had an autologous transplant using your own cells re-infused or an allo transplant using donated cells. Here's the autologous transplant timeline, and you recall from that earlier slide, here are the pre-transplant exposures, pre-transplant conditioning, fever, radiation, genetics, age, all of those things. You get those and then on Day Zero you get your stem cells reinfused, and then these toxicities kind of peak and decline, usually resolved by about Day 30.

(12:02): And these conditioning toxicities can be impacted by medication. Toxicities that can cause kidney issues, other issues, and infections can affect all organs. Once you get through all of that, many of these patients should be looking pretty good by about Day 60. And then there's a variable duration of tumor re-staging, but then lifelong surveillance is needed to monitor for the late effects of conditioning and/or radiation.

(12:30): Recipients of allogeneic transplants (using donor cells) face additional risks like graft-versus-host-disease (GVHD). So in the allo transplant timeline, it's the same as what I just described. But layered on top of that is this problem, this immune system problem, of graft-versus-host disease, which is this immunological attack mounted by the donor cells, and all manner of hosts or patient cells and organs potentially could be affected. And that results in half of these patients, if they develop chronic GVHD, taking about two to three years of needing to be on immunosuppression. However, this may extend out to well over 10 years in the minority of patients.

(13:04): And this little snakes and ladders or chutes and ladders metaphor here is to show the peaks and valleys of immunosuppressive tapers. Those of you who went through tapering off prednisone, coming off the prednisone, and then flaring and having to go back on, are well aware of the burden that that brings. But eventually patients do get out to the other side, to this holy grail of being durably off all immunosuppressive therapy. And if you're off your immunosuppression for a year, it's generally pretty unlikely that you'll need to go back on it.

(13:36): Chronic GVHD can create numerous health challenges. So why is chronic GVHD such a burden? Well, moderate to severe chronic GVHD is associated with a worse quality of life, higher symptom burden, pain medication use, and depression.

(13:46): The frequency with which people who have active chronic GVHD are unable to work is significantly greater than the one in eight not being able to work for patients with resolved chronic GVHD.

(14:00): We cannot forget the caregivers who have more depression and sleep disorders than the general population.

(14:04): And I showed you earlier that chronic GVHD can result in about two out of three people having a chronic health condition. If you have chronic GVHD, then the rate of a life-threatening health condition, moderate-to-severe-to-life-threatening, is about four to five times the rate of siblings.

(14:24): Long-term health care providers need to distinguish between chronic GVHD and other causes of health problems. So some of the causes of late effects. When you're picking, trying to pick your qualified healthcare provider, they need to be cognizant of how chronic GVHD can mimic symptoms in organs that can also be produced by conditioning toxicity, radiation therapy, or infection.

(14:40): And just to give you one example from this table. Dry eyes. It's not just all about chronic GVHD all of the time. The radiation therapy can affect the lacrimal glands and dry eyes, also dry mouth. But you can have infection. So demodex or mites are extremely prevalent. When you get an overgrowth of mites, this can definitely cause dry eyes. So you have to think about all of these possibilities.

(15:07): When I'm doing a comprehensive chronic GVHD assessment, I think of this twenty-point head-to-toe list, and it's sort of categorized in organ-based systems that are shown here on the left, systems-based problems.

(15:20): So your graft, what's the graft function like? What's the donor? Engrafting, we call that chimerism. Is that strong? Is it durable?  Immunity, immune reconstitution? So vaccinations are in this bucket. Are you ready for vaccinations based on your immune parameters, and so on: And then not to forget neurocognitive and psychological. And there's problems-based, chronic GVHD is a big one here, infection.

(15:43): Different diseases treated by transplant may create different long-term health challenges. And then this last bucket you also need to understand. So your healthcare provider, if you're not just being transplanted for a standard malignancy like leukemia or myelodysplasia, or a bone marrow failure like aplastic anemia, if you've got one of the more unique conditions, for example, Fanconi Anemia, which can have impacts outside of the bone marrow. These other areas outside of the bone marrow also need to be considered with long-term follow-up, because the Fanconi patient has a higher predisposition to malignancies. And so you need to understand what their late-effects risks are over and above the standard transplant situation.

(16:27): Long-term follow-up care should be a comprehensive examination of all possible causes of post-transplant complications. So long-term follow-up providers need to organize that list I just showed you. But every plan should have core elements for every survivor. And after our transplants, you need to be diligently monitored for chronic GVHD screening at least every one or two months. And particularly for up to a year after tapering immunosuppressive therapy, as I showed you before, you're not done in off-year immunosuppression until you're at least durably off-year immunosuppression for a year. So long-term follow-up care plans are also individualized and prioritized accordingly.

(16:59): And in general, what I do when I'm considering this prioritization, is this, my spheres of comprehensive relative view. And in the middle you always have to think pretty much with every visit, what is their graft function doing? What is the blood count, CBC? Are their donor cells fully there or are they declining? Do you need to monitor the health of their graft? Do they have too much iron in their system that you have to address with your blood-letting or phlebotomies?

(17:27): And do they have chronic GVHD? Is it new? Is it evolving? Is it responding to therapy? Whenever patients are on immunosuppression, you're always worrying about are they on appropriate antibody prevention? Are they getting their vaccinations?

(17:39): Then moving beyond that, at least once a year, you need to think about their bone health and their hormonal health. For example, thyroid levels need to be checked in everybody. Growth and puberty in children and adults, there's fertility, premature menopause, et cetera. And then all of the major organs, liver, heart, lungs, et cetera.

(18:00): Then general health maintenance, the same thing that you'd be getting with your regular PCP, looking at stuff like your body mass index, blood sugar levels, blood pressure, all of those things, nutrition. And then we must screen for subsequent cancers, and even more so if you've got a genetic predisposition syndrome, like Fanconi anemia, as one example, and there are many others. And then always you need to consider the whole patient from a psychosocial quality of life perspective.

(18:35): How is long-term follow-up best conducted? So you've heard what it involves and what needs to be done. And this speaks to the models of care. So this is roughly, I checked on this yesterday, somewhere between 4,000 and 6,000. So 5,000 is a reasonable estimate of accredited US hospitals. Only about 3-4% of them contain a BMT center.

(18:58): Only about half of transplant centers have their own follow-up care clinics. And so the ASTCT, American Society for Transplantation and Cellular Therapy, several years ago conducted a survey about long-term follow-up and we had a reasonable response rate for that type of survey. And only about half of them had a long-term follow-up clinic. And most of the survey respondents said that nurse practitioners and physician assistants were essential to running these clinics and that allo transplant recipients should be seen lifelong and the clinics were important to providing preventive guidelines.

(19:31): Now, just over half of the centers did not have a long-term follow-up clinic, but interestingly only about 28% felt they had too few patients to establish an LTFU clinic. So that begs the question, well, why is that?

(19:45): Well, partly the answer is that the majority of providers who answer the survey prefer to provide survivorship care as individual practitioners. And then a hundred percent of the survey respondents said that allo transplant survivors have needs that are separate from GVHD, and those transitions that I talked about being watched for follow-up, particularly when you're going from pediatric to adult, or away from a transplant center, that's a problem and can lead to complication.

(20:16): There are several obstacles to providing sufficient long-term care facilities. So the obstacles to long-term follow-up clinics are a lack of expertise in smaller centers, the logistics, where do you put them? What's the infrastructure required?

(20:25):  What is the commitment? And there also needs to be a physical commitment to them. And then as I mentioned, presence for an individual practitioner continuity care model is a bit of a barrier.

(20:38): If you look at the availability of subspecialists at these BMT centers who have long-term follow-up clinics, there are some deficits in important areas. So not everybody had a way to deliver vaccines. Not everybody had gynecological services, about 25% did not. There was missing psychology. There was missing orthopedics, dentists. And medical photography, if you cannot document baseline photos of skin, mouth, range of motion lesions, it's kind of hard to follow these patients diligently. So that's a big deficit as well.

(21:13): So the model of long-term follow-up care often depends on the transplant center size. Smaller centers, going down to as little as 50 transplants a year, it's usually individual providers following a small patient panel. If you go up to that 100 to 200 transplants per year, there may be some continuity clinics. And if you have a large transplant center like the one that I come from in Seattle, you have a dedicated long-term follow-up department with expert long-term follow-up providers who rotate. And it can also be LTFU continuity clinics. I have this actually in my pediatric practice here. So there's no rotation in that model. And you can actually have a hybrid model, which I think deserves further exploration.

(21:56): So looking at the small transplant center, this is the single provider who's a jack of all trades. They're managing the patient from diagnosis through to transplant, consult, delivering the actual conditioning and early transplant care, and then they follow them afterwards. That certainly provides better continuity. It's easy to establish rapport that way. There's the efficiency of knowledge by that legacy of continuity, and patients and providers often prefer this model. Who wouldn't want to have their one physician or care provider going throughout their whole survivorship?

(22:32): Smaller transplant centers may not be able to provide adequate long-term care. The cons are it's harder to develop adaptive chronic GVHD playbook scenarios at a smaller center. If you think about what I showed you, if you're only doing transplants 30 a year and the chronic GVHD rates are down to about a third, that's only about 10 patients a year. And not all of that chronic GVHD will be necessarily moderate to severe. So there's minimal to no chronic GVHD subspecialty expertise at these smaller centers and the jack of all trades may be too stretched to do justice for chronic GVHD long-term follow-up patients. They could be a limited experience with the full range of LTFU effects.

(23:05): Now obviously these are generalizations, but I put them down there just to document some of those possible issues. At a slightly larger standard or considerably largest standard really, 100 to 200, you can often leverage non-BMT cancer survivorship clinics where then you can get some of these subspecialties that are relevant. But the pulmonologist who sees only cancer survivors and not BMT survivors may not be as adept at managing complications of the ones that are related to the donor immune system.

(23:41): So the pros of this model in terms of continuity vary from moderate to high, and subspecialties are more available. It can work well for autologous transplants because there's no GVHD. There's higher access to cutting edge chronic GVHD therapies on research studies versus the small transplant center. And patient providers again, prefer this continuity model.

(24:03): Larger transplant centers face their own challenges in providing long-term follow-up care.  I think I won't go through these because they're pretty self-explanatory for the cons. So at a largest center like my own, the pros are that the continuity suffers in rotational models. But there is a deep knowledge of chronic GVHD. There's a full spectrum of subspecialties. There's the highest access to cutting-edge chronic GVHD research therapeutics and telemedicine can assist in management in remote home towns.

(24:34): However, this is mostly an unbillable service in its current state, needs to be explored a bit more. The cons of this model are, it's harder to maintain rapport in the rotational model. There's limited capacity to have a large survivor panel. There's a finite capacity which limits the in-person consultation to more complex patients or annually, and hospital administrators need convincing why these longer clinic visits are necessary for this consultative model.

(25:05): Patients who live far from transplant centers may have to rely on telehealth or outreach programs. So what about patients who live far away from the NCI-designated cancer centers? So here's a map of Washington State. You can see Seattle. And if you're outside of Spokane or the Tri-Cities, which are the two other largest towns about three to five hours away, you come from one of these little tiny towns in the middle of the state with limited resources. So these patients would have to drive to Seattle for their long-term follow-up and that can take this many hours if it's not snowing. And you could imagine if you're from one of these little dots up here, on the border between Washington and Canada.

(25:42): So how do we address this? Well, telehealth and outreach, for example. I run a pediatric outreach BMT clinic in Spokane four times a year. And we've now extended that to Anchorage, Alaska, which is a good way to keep patients in their town and form really good bonds with the people in those referring centers and help them become more adept, conducting your clinic up there versus remotely.

(26:12):  There are several models of follow-up care based on how many providers are involved. So the long-term follow-up models for care. This is the jack of all trades traditional model, where that one provider is solely responsible for the patient panel. And this is generally a small transplant center option.

(26:26): There's this shared survivorship clinic cancer selection model, where you're leveraging those cancer clinic infrastructures, but they tend to lack the chronic GVHD expertise relative to the largest model here at the end where there's dedicated BMT, long-term follow-up clinic.

(26:44): And so in our own situation where we have 6,000 prevalent survivors at the Hutch, we obviously can't see all of these patients back all the time. So the communication approach is what we need to work on to address a large patient panel. And traditionally that's just been with the transplant center entering or interacting with the patient in a to-and-fro situation, advice, info.

(27:09): A collaborative model of follow-up care where patients see both their transplant providers and their primary physician is ideal. Whereas what we practice in Seattle, which I would propose is the better way to go, is this collaborative patient, providing info to both the transplant center and to their primary care provider. And advice is flowing in all of these different directions to keep people on the same page and get what needs to be done for the patient in the best manner possible.

(27:31): The “Seattle approach” has been one of the more effective long-term care follow-up models. So this is a little bit more detail on what our Seattle approach is. We have a collaborative consultation service with telemedicine. We get about 20 to 25 calls per day, and it's over a hundred per week. These are triaged by the patient care coordinators who work with our nursing providers on the phones. And these calls are whittled down and you can see these loops over here between the nurses and the patient coordinators, there may be requests for photographs for example, of the skin of the mouth, of range of motion, lab reports, imaging reports, any diagnostic reports, patient records.

(28:12): Those all get funneled in here and a patient may be presented to the long-term follow-up attending on rounds which occur four days a week. And we sit down in the room with these nurses, with the patient care coordinators, sometimes there's other guests, pharmacists. And we review the info, the data. We make an initial plan. We may have to bring this back to rounds one or two times per week, sometimes more as information comes in. And eventually the case is closed and that's documented in the medical record.

(28:52): But this may result in consults going off to pulmonary, to ID. With the care everywhere, we can often push medical records and review lab trends. And we can do a pretty good job, but it takes a lot of time. It takes iterative rounds to do the best thing for these patients who are remote, and sometimes those remote visits are in the "too hard" basket, and we need to bring them to Seattle for a work-up.

(29:22): So does this work? Well, we think it probably does, but we need to study it more. There was a Seattle study that was conducted, published in 2016, that found no impact of distance for urban-rural residents on clinical outcomes. So that was encouraging.

(29:36): There was also this registry study that showed good survival after chronic GVHD for low-risk patients, but there were step-downs in survival for the higher-risk patients, which they categorized in groups two to six. And that was fully explained by step-ups in non-relapse deaths.

(29:53): So what this is telling us is the patients who are the sickest, most high-risk may succumb to non-relapse deaths. But in contrast, the Seattle study, this was published in 2014, showed better survival for high-risk groups, similar to the grading that was done in CIBDMTR (Center for International Blood Donor  and Marrow Transplant Research). And that was explained by basically no increment in the non-relapse deaths. Now it's not factually proven that that's because of the Seattle model. But you could postulate that because of the approach that I just explained to you in detail, which may be attributed possibly to the dedicated long-term follow-up program in having a robust telemedicine service.

(30:39): Survivorship plans are a good idea although their specific benefits have yet to be fully studied. So what about survivorship care plans? So this is a randomized study published in 2019 that tested where the survivorship care plans that were mailed to a transplant survivor. Half the patients got mailed these survivorship care plans that were created by the CIBMTR, whether they would improve confidence in survivorship at six months compared to baseline. And they ascertained whether this was the case based on phone surveys. And you could see that they had a pretty high completion rate for a phone survey, 87%. That's amazing.

(31:10): So among the 500 patients that they surveyed who were about one to five years post-transplant, only 37 didn't complete the baseline survey. That led to 458 being randomized, and about half of them got a care plan and half of them just got standard of care.

(31:27): And what we learned from this study was that survivorship care plans did not in fact improve confidence in survivorship information or the knowledge of BMT exposures or healthcare utilization. However, they did reduce treatment distress and the mental aspects of quality of life. So, a long way of looking at this is that they were oblivious to these things here, blissfully oblivious because they had reduced mental distress and those aspects of quality of life. So clearly survivorship care plans are still considered valuable, but more work needs to be done to understand what benefit they bring.

(32:06): So in conclusion to this, one-size-fits-all clinic specifications are not feasible. Center size and resources vary widely. The relative merits of a shared long-term follow-up clinic integrating single continuity providers versus centralized clinics having a rotational provider model are really unclear. We need to accommodate survivors at a distant location from the transplant center, because as I showed you, not everybody can live close to one of those 177 transplant centers. It's just not feasible. So we need to figure out how to do this.

(32:46): An ideal BMT long-term follow-up program has several characteristics. So what are the characteristics of the ideal BMT long-term follow-up healthcare provider? So this is the punchline for you. I think they need to be committed to the needs of this population and critically understand that early detection of chronic GVHD is vital to survive as quality of life and even life expectancy.

(33:05): These late effects have latency, right? They can come on 7 to 20 years later, and survivors need annual follow-up even if they look fine. There should be a focus on core elements and then those outer spheres that I showed you tackled at least annually.

(33:22): And you need to conduct robust monthly symptom evaluation exams and medication reconciliation. We don't want patients staying on a bunch of meds that all interact forever and ever. You should be always trying to cull down the medication list. Now frankly, it can be hard if you're on immunosuppression, but that should still be the goal.

(33:42): And this person authentically needs to commit to collaborative communication with the transplant center. And that communication needs to be timely and thorough and bidirectional. So the onus is on the transplant center also to report that promptly to the patient and the referring provider.

(34:01): Certain barriers remain to achieving this ideal model. So the barriers to finding this ideal long-term, follow-up healthcare provider are that not all patients live close to a transplant center, let alone in high volume one experience with clinic GVHD management.

(34:11): The bandwidth of some providers is so stretched that there could be insufficient time to address even the core elements, especially thorough exams to check for GVHD. And non-reimbursement for time spent communicating with the transplant center can be an issue. And not all transplant centers have a well-developed telemedicine service.

(34:30): There are some key takeaways to having an ideal follow-up care experience. So the takeaways are that long-term follow-up starts about six to hundred days post-transplant and it's more complex after an allo transplant because of the chronic GVHD. These care models vary by transplant, center size, feasibility, MD preference, patient, hometown location, and resources. So I can't sit here and say, "You've got to do it one way." We have to be flexible, and we have to make each of those models work.

(34:58): And I think what you need again is to find a provider who understands what needs to be done. And you can be proactive, showing them what needs to be done based on the content of this presentation, and whether they are willing to work with the transplant center. And I think we have great relationships with different sorts of providers, so I don't think I can pigeonhole them into one particular category. Comprehensive BMT long-term follow-up starts with those core elements, moves to the outer aspect, always considering patient exposures, genetics, lifestyle, mood, and quality of life.

(35:35): And these survivorship care plans, although they reduce distress, determining their larger role needs more work.

(35:42): And keep in mind referring MDs prefer concise to-do lists over multiple page reports. And so I think some of the latest feedback is that's kind of what these referring providers want, is just what do we need to do? When do we need to do it?

(35:56):  And telemedicine plus and minus, perhaps some outreach clinics, are likely key elements to delivering long-term follow-up to a growing number of BMT survivors spread far and wide.

(36:09): And with that, I'll be happy to take questions.

Question and Answer Session

(36:13) Sue Stewart: I have ocular and skin GVHD and have trouble finding doctors familiar with this. What do you recommend?

(36:24) Dr. Carpenter : Those are great questions, and ocular GVHD can be particularly troubling. First of all, my question would be if you're in a small town, it may be difficult, so you may need to travel to a larger town. But if they can ascertain that you have dry eyes and it's caused by a corneal problem, one of the things you can do is ask for the report, the diagnostic report, and if they mention some of the terms, keratoconjunctivitis or sometimes another term they use is superficial punctate keratopathy. If you have that in the diagnostic report and you only ever had this problem post-transplant, then I think there's a high likelihood that it's transplant-related. And there you can reach out back to your transplant center and say, "What would you recommend for this situation?"

(37:38): We have patients in small towns and sometimes that's the situation they're in. They diagnose dry eyes, but they don't call it chronic GVHD, and then when we look at the reports, it sure smells like it. So then we try to provide some information that will help the local eye doctor follow the patient.

(38:00): The other thing we do, if they come back to their visit for Seattle, we schedule them with one of our local ophthalmology teams that are very proficient and well versed in ocular GVHD.

(38:13): For the skin question, I think that depends on specifically what your skin disease is. That's a little harder for me to answer because there's lots of different skin conditions. But if it is GVHD-related again and probably a similar approach. You can get the diagnostic reports, and then run that by your transplant center.

(38:37) Sue Stewart:. Next question is what frequency is appropriate for DXA scans with known osteopenia and continued use of steroids for chronic GVHD?

(38:50): Dr. Carpenter : I think I'm going to add another part of that question. I think it's not just the frequency of DXA scans, but if you're treating the osteopenia with a medicine like a bisphosphonate, which could be given orally or intravenously, the intravenous dosing is usually once a year. Another question becomes how long should you continue to treat it?

(39:11): So if I have a patient who has osteopenia or osteoporosis, the more severe form of bone loss, we treat, for example with an annual injection of a drug and we follow the DXA scan annually. In contrast, if a patient just got prednisone therapy for their acute GVHD, and we do their DXA scan at a year and it's low. And they're off their prednisone and they have no chronic GVHD and they're not needing any other prednisone in the future, then I may or may not treat it depending on how bad the osteopenia is. And do a follow-up scan in a year, and once it's clear that the bone mineral density is stable and appropriate or it's improved, you don't necessarily have to keep following those DXA scans annual. So you're correct that the ongoing steroid use and ongoing treatment usually prompts an annual DXA scan. Hopefully, that answers your question.

(40:11): Sue Stewart: Thanks. The next person has a question. I don't know if it's going to be easy to answer, but I'll give it to you. “I'm 76 years old. I'm 12 years out. My BMT clinic is two and a half hours away. There's a shortage of info. Family physicians in our small northern Michigan town have a shortage of info. My local family doctor is retired as has his PA. The new staff often has no clue about the implications of leukemia and some have never heard of GVHD. Help. What do you suggest?"

(40:49): Dr. Carpenter: Yeah, that's a tough one. So it sounds like your town is small enough that there are really not many options for another provider. I think probably what I would do, I guess I would ask your transplant center whether they have any advice on who they've partnered with. I mean, for example, if we're asked that same question in Seattle about towns outside, towns that are more than two hours away from Seattle, we generally look to see who we've worked with in the general vicinity in that location.

(41:30): If you really cannot find anyone, then I don't think you've got a lot of choice but to at least get some follow-up with the transplant center annually. I mean, if you've got chronic GVHD and graft-associated disease, that's more problematic. But if you don't have any GVHD, then the screening generally is able to be done on an annual basis.

(41:56):  If you have chronic graft-versus-host disease, that's more problematic. And I think you need to find someone who is willing to work with the transplant center. And that could be a nurse practitioner, physician assistant or a really good generalist. But I would just pursue trying to find someone who can work with the transplant center. But it's a two-way street. The transplant center has to also want to work with them.

(42:20) Sue Stewart:  Yeah, that's a really difficult situation. We hear too much of that. The next person says, "The presentation appears to have been directed primarily to allogeneic transplant patients. Is it as urgent for autologous stem cell transplant patients, that they have long-term follow-up care for life?"

(42:43):  Dr. Carpenter: I think, it's not a one-size-fits all. So the autologous, if you remove the chronic GVHD element, the lifetime follow-up basically revolves around the toxicities of the exposures. So if you had an autologous transplant that involved high-dose traditional chemotherapy and/or radiation, a lot of the late effects monitoring still applies. Because you would still be at risk for long-term second cancers and sort of late organ problems for metabolic things as well. But they are more frequent with allo transplants.

(43:21): But I still think you would need to be followed for surveillance screening. For example, if you had full-dose radiation, you would need more regular screening, for example, for women, you'd need more regular mammograms. Colonoscopies would start at an earlier age than the general population. Those are just a couple of examples. You definitely need to be followed by your dentist for head and neck cancers and screened by a dermatologist or somebody who's at least looking at your skin from top to toe at least annually.

(44:00): Sue Stewart: All right, the next question is similar to the earlier question we just had, but perhaps you have a different spin on it. "This is a great presentation, but how do I find a good doctor in a small town? What should I be asking the doctor? What do I tell them when I'm interviewing a new doctor in order not to scare them?"

(44:21): Dr. Carpenter: Not scaring them is the key. I think the first question is, well, "Have you ever looked after a transplant patient?" If the answer is no, you'd like to be able to say, "Well, my transplant center is willing to offer you pretty specific guidance on the key things that need to be screened." And then I would show them that list.

(44:48): If we send a list to a patient or a provider, we can generally get buy-in or not from that provider as to what they're willing to do. I think so long as that provider in the small town can be reassured that they've got a hotline to your transplant center for someone who can partner with them on the tricky questions, then that generally turns that into a more workable situation.

(45:13): But again, it's that bidirectionality. So I think another question that I would encourage transplant candidates to ask of their transplant centers is, "What does your long-term follow-up care look like? How do you partner with my doc in my small town, when I go back to my small town?"

(45:35): So you may or may not have a choice of the transplant center also depending on where you go, but if you can establish up front that long-term follow-up with one transplant center is substantially different from another transplant center, that's another choice that you can make up front, right?

(45:54): Because that communication is bidirectional. You need to know both aspects of the chain. Does the transplant center have the infrastructure to work with your local doctor?

(46:06): Sue Stewart: I think that's a good point. The next question is from a person who wants to know how a post-transplant patient can have a high quality of life in Florida if they live in a coastal area. "My husband is terrified of going outside and participating in any outdoor event."

(46:29): Dr. Carpenter: So there's a lot under that question. I'm going to make the presumption that the high quality of life in Florida is being able to be exposed or walk about in the high sunshine area. But there can be other aspects too, in terms of what is the herd immunity to vaccines and things like that.

(46:54): But I think, let's just take the sun exposure. You could totally, I mean I grew up in Australia, right? We do transplants in Australia. You just have to deal with it, and the best way to do that is sun protection, appropriate UVA, UVB, sunblock, and you can also get UVA, UVB clothing. So you can definitely do all of those things outside, but you have to understand that your lifetime risk of radiation it all comes at once and that's what gives you that anywhere from two- to fourfold increased risk of skin cancers, that you need to double down on protecting yourself. You also want to make sure you've got good eye protection, UV eye protection, et cetera. Things like that.

(47:38): As far as earlier post-transplant and being worried about infection, I always think about the risk to benefit. I would argue that in general, getting out and about and doing stuff is so much better for your mental health, physical health. And after all, you have to transplant to get on with your life. You don't want to live in a bubble and stay at home all the time. So I would encourage you to get out and just be sensible about hand washing in public spaces. If you want to wear a mask in crowds, that's your prerogative. But the sun protection is something that you can also pretty readily do.

(48:14): Sue Stewart: Sounds like a good plan. This woman would like to know. "Do you have any websites; materials that you would suggest to give to a primary care physician that would help that doctor understand what he needs to know to help a cancer survivor going through GVHD?"

(48:34): Dr. Carpenter: Yeah... Probably. I mean, there's multiple ways. I'm imagining on BMT InfoNet, there's some basic distillation of that. A more detailed approach; there is the ASTCT Survivorship Guidelines that came out.  

(49:10):  So those would be the main things. But honestly, the transplant center in my mind should be providing that information. So when a patient leaves Seattle at Day 100, we send them a to-do list of what the monitoring looks like for the first four weeks after you get home and then monthly. And then, that sort of carries them through to the one year follow-up, and then at that one year follow-up, sort of like another bite of the cherry of education about, okay, now that you've gotten through the first year post-transplant, hopefully your disease is in remission. The focus shifts more into what is this late effect monitoring? What is that all about?

(49:50): And in the patient without chronic GVHD, you know it becomes pretty check boxy. So you just go top to toe, like that system. I mean, even if you have this slide set that is available to you as well, that gives them a basic idea on what things need to be looked at. And it's going, checking the CBC, your thyroid function tests, other hormone tests, looking at hormone function in your ovaries and testicles. Lung function tests, sugar, diabetes, blood pressure, all of that general health stuff as well is doubly important for a transplant patient because the risks of premature aging that are there for the general population are front and center in a transplant patient.

(50:42): Sue Stewart: All right. Next question. "Is it advisable to take sodium butyrate supplement to reduce the probability of GVHD?"

(50:57): Dr. Carpenter: I think what you're referring to there is in the pre-transplant situation, trying to prevent acute graft-versus-source disease. There are studies looking at resistant potato starch that can affect basically the intestinal microbiome composition. And so that's sort of related to the immune system. It's a very complicated answer to your question, but I don't see a role for sodium butyrate in the long-term follow-up setting. That's more something that people are looking at to prevent acute GVHD from developing or being severe in the early transplant period.

(51:45): Sue Stewart: All right. Next question. "I'm 69. I'm concerned about recent skin changes on the torso of my body. I live outside of a previously-seen hospital system who released me from their care to my general practitioner. Presently, I'm living in a rural area. The closest dedicated adult bone marrow transplant center is in a different medical system than the one that performed my auto transplant for lymphoma in 2014. What would you suggest? Should I go to the center or should I continue care through my general practitioner?"

(52:24): Dr. Carpenter: So to clarify, this patient has not had an allergenic transplant, they've had an auto transplant only.

(52:31): Sue Stewart: It looks like just an auto transplant, yes.

(52:33): Dr. Carpenter: Yeah. So in that situation there's no concern about these skin changes being graft-versus-host disease. I would probably, I mean, if you haven't followed up with your GP, definitely do that. But the next port of call would probably be a dermatologist.

(52:56): Sue Stewart: All right. So is it better to seek out follow-up care from a cancer center or a hematologist who maybe sees more blood cancer patients than a primary care physician or an oncologist who sees patients that have a whole variety of types of cancers, breast cancer, prostate cancer, etc. and may have less time to focus on the needs of a stem cell transplant patient?

(53:30): Dr. Carpenter: Yeah, thanks for that question, Sue. I mean, I think in all of the years that I've been doing this, and I've been doing pediatrics for a long time, but I've been doing adult long-term follow-up since 2001. And I have seen all manner of providers work well, meaning it definitely does not just have to be an oncologist or the obvious referring provider. If it's a patient with AML, for example, yeah, it'd be nice if that referring AML expert would be willing to partner with us to address the transplant-specific issues. And if they happen to relapse, then you can coordinate the relapse therapy also with that AML expert.

(54:16): However, if you do have an AML expert or oncologist who's so stretched or they don't have the bandwidth to partner in that authentic manner with the transplant center, then sometimes it's better to be seen by a provider who is willing to do that. And by that, it could be a physician assistant, nurse practitioner, a general doctor. It has to be someone who's good at communication, follows up on the details and can work with the transplant center to achieve what needs to be done. So I don't think I can say one person is better than the next. It comes down to the kind of basic characteristics of the provider's clinical care situation.

(55:07): Sue Stewart: Closing. So thank you for that. And with that, I think we'll need to wrap up the session.

(55:15): On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Carpenter for your presentation on this really important topic for transplant survivors. So many people struggle to find good quality care after transplant in their home area. And I want to thank you, the audience, for your excellent questions and have you contact BMT InfoNet if we can help you in any other way.