How to Protect Your Health after a Transplant Using Your Own Cells (autologous transplant)

Strive to Thrive! How to Protect Your Health after a Transplant Using Your Own Cells (Autologous Transplant)

July 12, 2020 Part of the Virtual Celebrating a Second Chance at Life Survivorship Symposium 2020

Presenter: Peter McSweeney MD, Director of Cellular Therapeutics and Director of Long-Term Follow-Up, Colorado Blood Cancer Institute (CBCI)

Presentation is 43 minutes with 10 minutes of Q&A.            Download Speaker Slides 

Summary: Learn about medical complications that can develop months or years after an autologous transplant. Learn how you can minimize the risk of developing problems and get appropriate treatment if a complication occurs.

Highlights:

• Individualized follow-up for each patient who undergoes an autologous transplant is essential for at least 10 years. ​
• Targeted therapies to prevent relapse after autologous transplant are necessary since transplants using your own cells tend to be less potent than those using donor cells.
• Preventative health maintenance, cancer screenings and an active lifestyle are key to good health​ after a transplant using your own cells.

Key Points:

05:10   The number of long-term autologous transplant survivors is increasing​ and in turn the need for survivorship care.

13:05   Use of CAR T Cell therapy after autologous transplant is available for aggressive B-cell lymphoma, acute lymphoblastic leukemia and may be beneficial for myeloma.

15:46   Evaluations and interventions for bone loss should be a part of your post- transplant follow up.

17:23   Patients will have significantly reduced immunity after auto transplant and will need to be re-vaccinated the first year after transplant.

25:25   The lungs and heart should be closely monitored since certain drugs used alongside transplant are known to cause late effect issues.

30:46   Neurological side effects, sometimes called chemo brain, can continue after transplant; review your medications with your doctor to see if any could be causing these issues.

31:59   Cataracts are often a side effect of radiation and steroids.

32:35   Secondary cancers can occur typically three to five years after transplant. MDS, leukemia and solid tumors are the most common secondary cancers for survivors of auto transplant.

35:09   Fatigue and sleep disturbance which are common after autologous transplant should be addressed with your care team.

37:16   Quality of life after autologous transplant often requires an acceptance of life changes and commitment to over all health with a focus on mental health.

Transcript of Presentation

00:02     [Moderator] Welcome to the workshop, Strive to Thrive: How to Protect Your Health after a Transplant Using your Own Cells. My name is Michala O'Brien, and I will be your moderator today. It's my pleasure to introduce you to Dr. Peter McSweeney. Dr. McSweeney is the Director of Long-term Follow-up and Cellular Therapeutics, at the Colorado Blood Cancer Institute (CBCI) at Presbyterian St. Luke's Medical Center in Denver, Colorado. He has worked in the field of blood stem cell transplantation, for more than 30 years and has directed or participated in many research studies, in the area of blood and marrow transplantation. Please join me in welcoming Dr. McSweeney.

00:49     [Dr. McSweeney] All right. Good morning everybody. Today's talk presentation is going to focus on transplantation using your own cells or so-called autologous transplant. I'm going to give you a little bit of an overview, of autologous transplants to start with. I know that some folks will be in the post-transplant setting, some will be caregivers or family members. Some will have little familiarity with this. And so I'm going to give you a little bit of background and then, move on and discuss some of the issues for following people after they've gone through this treatment, and what the implications of undergoing this type of therapy are for the future of your health.

Autologous Transplant Procedure

01:31     So just to summarize what an autologous transplant involves. The primary goal of the therapy is to, eliminate the underlying disease or reduce the underlying disease to a more manageable state. Involves the use of high-dose chemotherapy, in some cases with radiation therapy, to treat the underlying disease.

Now, the main components of an autologous transplant include an initial pre-transplant therapy, with just conventional drug therapy, or sometimes radiation to lower the amount of disease in the body. In many instances we hope to get way down and disease burden to remission status.

So, starting the transplant itself, we need to collect what we call stem cells, your own bone marrow stem cells. They can be used to grow back the bone marrow and the blood counts after the high-dose chemotherapy is given. This is generally done by giving the recipient chemotherapy with a growth factor or growth factor alone, and moving the so called stem cells out of the bone marrow into the blood, with that collected, by what we call an apheresis procedure.

The cells have been frozen with a freezing agent, and the patient can then move on to what we call high-dose chemotherapy or high-dose chemotherapy and radiation therapy, using one or more drugs and the radiation. And there may be a recommendation for some diseases to continue therapy after recovering from the transplant with another treatment to try and reduce the chances of the disease coming back or delay its return.

So, this exposes the body to the cumulative effects of all these treatments. And an important issue for us is that, as we become better during these transplants, the age range has extended. Older and less healthy patients can suddenly be taken through this type of therapy.

Autologous Transplant for Myeloma

03:29     This is just a simplistic schema for an autologous transplant for myeloma, which is the commonest form of autologous transplant. This is the actual high-dose chemotherapy procedure itself. These stem cells have already been given and so you can see on the left-hand side of the slide, the two days of chemotherapy with a drug called melphalan. On day zero, these cells are taken out of the freezer board and injected into the bloodstream, to regrow, and then the blood counts drop very low over a period of five to seven days.

During that period of time, most of the side effects related to the high-dose chemotherapy occur, particularly gastrointestinal side effects. And then there's a recovery phase usually starting around about, 10 days post-transplant where the counts begin to rise, and a lot of the side effects related to the high-dose chemo start to clear up. Usually, people were discharged from the hospital setting after being hospitalized for this procedure, somewhere around about 15 to 18 days after the procedure.

Diseases Treated by Autologous Transplant

04:31:  So, this is a summary of the main diseases treatable by autologous transplant. By far the two commonest diseases are multiple myeloma, non-Hodgkin's lymphoma, and then a smaller scattering of Hodgkin's lymphoma. Not very often do we treat leukemias these days with this treatment. And then in younger patients, particularly children, neuroblastoma is a more common form of transplant done. And more recently, there has been an emerging field of autologous transplantation for these two autoimmune diseases, scleroderma and multiple sclerosis.

Trends in Use of Autologous Transplant

05:10    And this is just a summary of trends in autologous transplant. And this illustrates at some level, why things are a changing landscape for both patients and physicians alike. You can see if you go back to 2000, on the left-hand side of the slide, almost all the patients were less than 60 years. And as we've come through the following two decades, we've seen a big upswing in the number of patients between 60 and 70 treated, and also very noticeably over the last 10 years or so a big upswing in patients over 70 receiving these types of treatments. And this represents an increasing understanding of, what people can tolerate and also the type of supportive care, and also to some degree, the ability to sort of manipulate these procedures to make them more tolerable for certain patients.

And this next slide here summarizes the use of autologous and allogeneic transplant. The allogeneic transplant is when we use a donor to give you the stem cells. You can see there's almost an exclusive use of autologous transplant for certain diseases, and exclusive use of allogeneic or donor transplant for the other diseases. You see the large proportion of patients undergoing autologous transplant, have myeloma and that's the commonest indication. You see there's a small number of patients with lymphoma who get donor transplants where far and large that's an autologous transplant disease. So, you can see this distribution and so you could understand, depending on the underlying disease we're treating, the pathway's fairly clear where we'll be going.

This is another slide that indicates the trends in autologous transplant usage in the United States over a couple of decades. You can see the big upswing in the use of transplantation for myeloma. In the earlier slide, it shows you where the main expansion is -it's in the 60 to 70-year-old population, which of course is, where most of the disease is found in the first place.

Goals of Autologous Transplant

07:17     So the main goals of autologous transplants depend on the underlying disease. And when we treat patients with lymphoma, where you're generally very focused on trying to cure the disease with the procedure, it tends to be a little bit more intensive than, say, the transplant done in multiple myeloma where we don't think many patients are going to end up with permanent control of their myeloma, but we know that the transplants can help people live longer. And also, a major goal is to try and prevent, recurrence of symptoms and fix the disease for as long as possible.

Outcomes after Autologous Transplant: Hodgkin Lymphoma

07:56     This next slide just shows some data on transplants for Hodgkin's lymphoma. And the point is that the status of the underlying disease influences the outcome. And when I say the status of the underlying disease, that is if it is still responding to conventional treatment with regular chemotherapy, we call that sensitive. You're going to do better than if your disease is resistant to the underlying chemotherapy. But you can see that even in both settings for this disease, long term control and survival can be achieved with this type of treatment.

Outcomes after Autologous Transplant: Myeloma

08:37     The slide here looks at outcome’s survival in myeloma, after transplant. And treatment of myeloma is multifaceted. It's not just transplant. It's a combination of therapies with which you frequently incorporate the transplant. You can see that, you look at these different time frames, if you go back to the 2001/2004 grouped at the bottom line, you can see there's been a steady trend upwards in survival in patients undergoing treatment.

And this most likely reflects the combination of therapies we're using for myeloma, and the improved drug therapies that we can use before and after the transplants. The transplants themselves are not really different to the way they were back in the early 2000s.

Now, one of the most important questions is, why doesn't transplant work for everybody? And this slide illustrates what the problems are. You can see that, in the blue part of the pie, is the major cause of folks not surviving after undergoing a transplant. And by far the biggest cause of treatment failure remains the underlying disease itself. You can see that 30% of death after transplant is related to other causes, and we'll touch on some of those as we go forward. But if one wants to really reduce death after transplant and improve outcome, we still need to focus heavily on preventing the primary disease. Or not so much preventing it but preventing it from coming back, and that involves strategies both before and after the transplant procedure.

Risk of Relapse after Autologous Transplant

10:25     So just talking about the issue of relapse, because it really is a very important issue to try and address in this setting. Autologous transplants have a little less potency than donor transplants for getting rid of the disease, but they have far less in the way of long-term side effects. So, the major limitation is that the disease can come back. Now the risk to that is dependent on the underlying status of the disease and the type of disease we're dealing with.

Transplants, when they were first being employed, were really one-shot treatments to try and do away with the disease. More recently, studies have shown that post-transplant maintenance therapies may contribute significantly to improving outcomes. And examples of that are shown here. The use of Revlimid is well established after autologous transplants for myeloma to delay progression of the disease and improve survival. There are subsets of myeloma who may benefit from other approaches, such as the use of Velcade or consolidation cycles of chemotherapy and even second transplants. Some of these are a little bit controversial. and what have you discussed with your own physicians for your own situation.

In mantle cell lymphoma, which is a fairly uncommon form of lymphoma, but for which transplant is quite important, it has been shown to do better if rituximab is employed for several years, if maintenance therapy.

And then in Hodgkin lymphoma, there's a subset of patients who benefit from post-transplant care with brentuximab. And more recently there was some other drugs being used such as, we call them checkpoint inhibitors, which are immune stimulators.

Treatment of Relapse after Autologous Transplant

12:10     So when we're treating relapse, we can have certain goals. It could include, a realistic approach that all we can do, try and suppress the disease further for a period of time that will help somebody live longer. We could have a goal of alleviating symptoms. And then in some instances, we're still focused on the possibility of curing the disease. Type of options that may be offered are summarized on the right-hand side of the slide. They could be through the chemotherapy. It could be clinical trials with newer drugs. Some of them may be trying to get the immune system up and targeting the cancer. In some patients, there may be an option for second transplant.

For patients with myeloma, that's usually going to be an autologous transplant. And for patients who have failed autologous transplant for lymphoma, that will usually be a donor transplant.

CAR T-Cell Therapy after Autologous Transplant

13:05     More recently, there's been the development of very innovative and exciting therapies, so called CAR T cell therapy, that has been used successfully to treat relapses of B-cell lymphomas. That therapy is not unique to that setting and is being expanded and may certainly have a big role in the overall treatment planning for blood cancers in the future.

This just a little bit more on that. Commercially available for aggressive B-cell lymphoma, and also available for acute lymphoblastic leukemia. It appears to be, able to put about 50% of patients with very resistant lymphomas into complete remission. And about a third of patients overall, between about 30 and 40%, still remain in remission several years after the treatment has been administered. We do think that for multiple myeloma, this may even have a greater use in the future. That the therapy will become available as a commercial product, towards the end of this year or maybe next year.

And to date, the major advantage of this, at least in the clinical trials performed, lies with inducing further remissions. And there appears to be a small number of patients with follow-up for several years, who are not relapsing within that time frame. These therapies, we think, will be more effective if employed at earlier time points in the disease, that is, before the disease becomes very resistant to the therapies we're administering.

Late Side Effects of Autologous Transplant

14:42     So let's talk a little bit more now, about the side effects of autologous transplant and how to deal with those. They vary considerably by transplant. The implications of some of these side effects are greater in younger patients and older patients. And we'll talk about a little bit about some of these as we go forward. You do have the ability to get any of these slides and go through them. And I won't go through every slide in incredible detail.

Bone Problems after Autologous Transplant

15:12    Now, one of the important side effects is going through treatments of blood cancers is development of bone problems. Particularly damage to the joints. We call that avascular necrosis. And this has been seen in patients who get a lot of steroids. Steroid use is very common in blood cancers, in upfront therapy, both in lymphomas and in myeloma. So, it's a risk for patients, and it's less related to the transplant procedures themselves, with autologous transplant, and more related to other treatments administered.

15:46     So we do see some bone thinning, which can be family history. Age and sex can contribute to this problem. This is something that can be, at least, partially addressed by undergoing appropriate evaluations and interventions. In myeloma, bisphosphonates - drugs like Zometa and similar drugs - are administered as part of the actual therapy, for bone strengthening. But to get a better handle on whether somebody is at risk of bone problems, particularly osteoporosis related fractures, then bone density testing would need to be done. And it's frequently employed as part of the post-transplant follow-up at various intervals to establish what's going on and trying to determine what the interventions should be.

Ways to try and reduce bone related complications include having adequate amounts of calcium and vitamin D, given, and often these are given as supplements. There may be a place for hormone replacement therapies, exercise, etc. Keeping physically active appears to be an important part of the bone preservation strategy. And then it can be an important role for getting a specialist evaluation by an endocrinologist who understands best how to manage bone metabolism and bone strengthening drugs. So those are some of the ways to try and deal with this. Good to discuss with your physician, as to whether there is a risk for you, these problems.

Immunity and Infection after Autologous Transplant

17:23     Another important area is immunity and infection after transplants. Almost everybody has reduced immunity of some significance after transplant. That's why you hear about precautions we would be taking to try and prevent you from getting infected. Obviously, it's a critical environment right now with the coronavirus spread in the community. We want people to be very cautious about their health and avoid risky situations that could lead to getting infected, because we know that there's a higher risk situation for getting an infection if you have been through a transplant, or you're going through chemotherapy, or even if you've been through just conventional therapy for any form of cancer.

Well, immunoglobulins refer to just having low antibodies being produced in your body, and that's a frequent complication of diseases that we treat and also the medications we give to treat the disease.

Shingles, which is a reactivation of the chickenpox virus, can be a very unpleasant experience for some people. And this would occur frequently if we didn't do preventative measures. Typically, we're giving the drug acyclovir, which is a preventative medication, for at least a year after autologous transplant. And also recommending vaccines against shingles be employed after transplant. We know that these outbreaks of shingles can occur after the discontinuation of the prevention, so that points to the importance of the vaccination.

And then pneumocystis which is an infection that was primarily seen in the AIDS population many years ago as a complication of immune suppressing chemotherapies and transplant. So, we typically give people preventative medicine to try and stop this. Usually after autologous transplant for six to 12 months. And this often involves a drug called Bactrim which is a cheap, simple antibiotic to administer.

And then we know that with the immune damage that occurs with these treatments, that we ought to vaccinate people after transplant against infections that they were vaccinated against when they were a child. The guidelines for this are available at the CIBMTR Post-Transplant Guidelines tab. I'll go on to talk a little bit about that in the next slide.

Vaccinations after Autologous Transplant

19:53     So we typically initiate vaccinations to try and boost immunity, somewhere between six- and 12-months post-transplant. Some centers like to do this earlier and some like to do this later. I don't know that we can say absolutely what the best approach is. Immunity and the ability to generate a response to the vaccine is probably going to be better the further you get out from the transplant. On the other hand, you don't want to delay too long and expose patients to the risks of these infections.

There's a fairly standard schedule of the vaccines administered, from the time point that they start, which is time zero there tends to be series administered at that point, followed by boosters at two, four and 12 months, depending on the type of vaccine that we're talking about. What we call live vaccines have some risk of causing infection in recipients and are generally not given early after transplant - generally delayed until at least two years out to transplant and avoided if ongoing immune suppressant chemotherapies are being administered.

Now the shingles vaccine was tested for early use after transplant. And although it probably would be more effective numerically, the number people who'd respond really well to it is delayed a bit further. The trial that showed the effectiveness of it was employing it given at two- and four-months post-transplant. Now I personally think this can be delayed a little bit, because the acyclovir here is actually a very good drug for preventing reactivation. But if you want longer term immunity, then the vaccine is going to be important.

Another important vaccine is the flu vaccine, which can help diminish flu like symptoms or even prevent significant infection. In general, this is given once you've got some immune recovery, although I generally favor trying to give this vaccine to anybody who's got blood count recovery after the transplant, because, it's an important infection to try and prevent the best we can. There is some evidence we've found from the shingles vaccine, that early vaccinations do prevent, or at least generate some immunity against, the infections we're trying to target. And the flu vaccine is not a permanent vaccine that needs to be repeated every year. Your health care provider should be getting their flu vaccines, to try and keep you safe.

Fertility after Autologous Transplant

22:16     So moving on to another important subject, fertility after transplant. Now, this obviously is more important to some patients than others. And much more important to younger patients than older patients.

Because the vast increase in patients over 50 and 60 getting transplants, particularly for myeloma, you can see that we probably don't have to discuss that a great length with many of the people undergoing autologous transplant. However, one important concept is, that the transplant is not a universal contraceptive. And while in the early days of transplant, it was clear that a lot of patients were becoming infertile. as we've sort of moved to different regimens, the fertility or infertility risk is less well defined. And probably more patients getting current regimens that don't have radiation - and radiation is not used very often in autologous transplant now - there's a greater chance of fertility preservation, particularly in younger men and women. And men tend to be a little bit more resistant to the effects of these transplants in terms of infertility than women. In order to try and optimize, to tell, the best time to discuss this is before the transplant. And options such as sperm and egg banking or storage of ovarian tissue, that should be undertaken before the high-dose chemotherapy is administered, to best your chances of fertility post-transplant.

These are things to discuss with specialists in the area and get referrals from your oncologist before you get to the transplant phase. Sometimes, there are good opportunities for doing this, depending on what's happening with your cancer. In other situation, there may be a more difficult, challenging situation with the cancer that they make effective storage more difficult.

Sexual Health after Autologous Transplant

24:20     Sexual function after transplant, most centers are providing some guidance on resumption of sexual activity. Certainly, the high-dose regimens can induce menopause in females. And this is more likely to occur with certain regimens that are more toxic to the ovaries and also with an older age.

So, if you're pre-menopausal, you're in the 40s, you're more likely than, if you're in the 20s, to experience this. Now sexual function can be impaired by these hormone changes that go along with this side effect, and this is where having discussions with your doctor and getting input from specialists, such as endocrinologist and sometimes sexual specialists, can be very helpful. Let's say that most oncologists are not terribly well trained to go into depth in this area, although they have a good understanding in general of what the issues are.

Pulmonary Problems after Autologous Transplant

25:25     Another area that was probably more of a problem in the past, but still is a persisting issue to consider for some patients, is development of lung issues after transplant. And these are usually cumulative from treatments that occur before the transplant with certain medications, and they can be related to some of the drugs given during the transplant.

For example, the drug bleomycin is used both in treating Hodgkin's disease and testicular cancers and can lead to some lung damage in patients. And they interact with some of the transplant medicines to make this worse. Radiation in particular, it's administered to the chest - and that would be one of the reasons for getting the disease because a lot of the radiation administered in lymphomas, it's actually administered for disease in the chest - that can have implications for interactions with the transplant chemotherapies. And techniques for more tighter radiation fields that don't scatter as much have been developed, but still is an issue that we need to be aware of, as we are administering these treatments. The net effect is it may be some loss of lung function, either from the radiation or in some cases even from surgery to try and remove areas of infection which, while not a very common scenario in autologous transplant, is occasionally seen. hen there may be some effects on the tissues around the lungs, like we call the pleura, from some diseases or some infections that may diminish lung function.

So, what can be done about these? Well, this is really going to require the appropriate monitoring. And that would include testing such as lung function tests. In some cases, scans of the lungs to identify what the problems are. And then the use of various specialists, typically the lung specialist to determine the need for medications, any procedures that may help the lungs function, sometimes courses of steroids to reduce inflammation in the lungs. And then really, probably the most important thing is, not smoking because that's contributed to lung disease in any setting. Avoiding toxins that might be toxic to your lungs, through ventilation. Some people are more sensitive to these and others. So, these are things I can think about do to try and protect, the breathing after transplant.

Heart Health after Autologous Transplant

28:05     Another important organ for long term health, of course, is your heart. Now, depending on the type of treatments you get. Before and with a transplant, there are greater or lesser risks of the therapy on how the heart functions in the future. In general, the treatments that are administered and the potential effects on the heart do interact with general health issues that might affect the heart, such as high blood pressure, diabetes, high lipids. And so, addressing underlying general medical issues can help with cardiac health after the transplants is performed.

Now one of the major risks for heart problems after transplant is the exposure to what we call anthracycline chemotherapies. And these are drugs, particularly Adriamycin that are used in treating both Hodgkin's and non-Hodgkin lymphoma. So those patients tend to have a little more risk, and those drugs are not typically used very much in myeloma these days.

Another potential compounding factor could be if radiation was given to the area of the chest, involved the heart. The chemotherapies that we actually give during the transplant, may have some bearing to some patients that are going to get high doses of cyclophosphamide, which can be a heart toxin. The drug melphalan, which is used for treating myeloma, is usually not, for most people, going to cause significant effects on the heart function. And it would be more likely to do so if there was pre-existing reduction in your cardiac functions.

Again, that speaks to why we do the pre-transplant workups, such as cardiographs and echocardiographs, to try and get a handle of how good the heart is working and how strong it is, before going into the transplant procedure.

So, what can you do about heart health? Well, I talked about the risk factors. Regular exercise can be an important contributor to well-being. Regular checkups, reporting symptoms that might develop, such as shortness of breath or swelling in your legs that might indicate some problem with the heart. Increasingly, there are what we call cardio-oncology services, and specialized units where the cardiologists working directly with oncologist to try and provide optimal care.

Neurological Side Effects after Autologous Transplant

30:46     Neurologic side effects can be important after transplant. You've heard of the condition people call chemo brain. In terms of trying to influence the outcome of that, it is not very well understood how best to do this. But keeping the brain active, keeping your brain engaged is probably one of the most important things. Talking to the physicians about medications you're taking, that might be contributing to an inability to use your brain normally, giving enough time after transplant to recover, these are some of the things that can help.

There is a common problem called peripheral neuropathy. This is very common in chemotherapy given to both lymphoma and myeloma [patients]. And we're trying to develop regimens that are less toxic to the nerve. That long term numbness and tingling can be an annoying problem after both front-line chemotherapy and then transplant. These, again, are primarily treated with symptomatic treatment. In some cases, it will get better over time, in some cases, also, it will completely disappear.

Ocular Side Effects after Autologous Transplant

31:59     There may be times when the eyes are going to be affected by the exposure of therapies. Cataracts has been a classic complication of transplants, although it's more typical of radiation-based treatments than the high-dose chemotherapies we currently use for autologous transplant. Another important factor is exposure to steroids, and continuing large doses or intermittent large doses, that can accelerate the development of cataracts. And again, this is an area where there may need to be specialized help.

Secondary Cancer Risk after Autologous Transplant

32:35     One of the most important side effects of intervening in cancer, through drug therapy or transplant, is the risk of new cancers in the future. And this slide here, if you look at it, it illustrates three different types of cancerous process post-transplant. In general, the MDS, leukemia and the solid tumors are the ones that apply to autologous transport. We don't see these post-transplant lymphoproliferative disorders very much at all in autologous transplant setting. MDS or leukemia is damage to the bone marrow. It's a chemotherapy and radiation side effect. It generally occurs in the two to five-year range after the transplant and is manifested by worsening [blood] counts.

This is probably the most serious side effect we worry about after transplant, because it's harder to treat than, a lot of the other things that we may encounter. Solid tumors, which are cancers in other sites apart from the bone marrow, tend to gradually accumulate over the years. And if you look out it 15, 30 years out, we're going to see somewhere in the range of 10 to 20% of patients have to be treated for other cancers. Often these are manageable. Obviously, depending on where they occur and the type of cancer, that would affect the likely outcome of any treatment. And the most important thing about solid cancer is trying to catch them early, when they're treatable and can be taken care of surgically. So therefore, this is a reason why we recommend regular follow-ups after the transplant to keep an eye on these potential problems that could develop and, work out how to intervene at an early stage.

So, this just summarizes the two main secondary cancer groups. The AML and myelodysplasia population problem, four to 5% in the first four to five years after transplant. And some risk factors such as radiation, low stem cell doses and focus radiation to various parts of the body.

All right. So, what can you do? Well, we talked about this health maintenance, take care of yourself, regular surveillance of your health. Avoid cancer causing types of activities such as smoking and drinking a lot. And then having a good summary of your health care from the past, for your current doctor is always important, so they know what you've been dealing with.

Fatigue after Autologous Transplant

35:09     An important complaint after transplant is fatigue. This is sometimes difficult to pin down as to what's causing it. There are so many different possibilities. These are sort of summarized on the slide. I'm not going to run through the slides, because of time but you can sit and look at this.

When we're kind of looking at a patient who's complaining of fatigue, we have to kind of work through the possible causes and see what we can best address and how to best give advice on managing these issues. So, we will look at the nature and effects of fatigue. The typical chemotherapy complications of fatigue, one expects that to gradually improve over time. Some patients actually recovered quite well after autologous transplants within a month and some take quite a lot longer. Some patients still complain of effects even several years later.

Physical rehabilitation and exercise are probably an important component to getting back going again, getting over the hump of what the treatment has caused. Somebody's continuing to experience coexisting medical problems and psychological issues can be important, obviously, to address those. Nutrition is important. There may be a role for what we call cognitive behavioral therapy to deal with some of the inertia that can go along with the psychological issues. Trying to match your energy to activities, obviously a key point.

Sleep Disturbance after Autologous Transplant

36:35     Sleep disturbance is also an important issue, just like this can affect anybody in the population. Some more significant problems when you've been through such difficult treatments is the form of post-transplant or post-treatment trauma that's sort of persisting for some patients and needs, sometimes, to be addressed very specifically. You're experiencing neuropathy, depression, anxiety, if you're on steroids. - these all can be a contributing effect as in they... they need to be discussed with your doctor because there may be interventions or advice you can receive, that will help with this.

Quality of Life after Autologous Transplant

37:16     So what about quality of life after transplant, and who does okay? And who doesn't? There's a fair amount of anxiety post-transplant, there is your vulnerability because of the uncertainty of the future. One's own personal life can be obviously affected by some physical effects and the psychological effects of this. Nonetheless, there's a fairly high percentage of patients who return to a good level of functioning post-transplant. Many return to work, and many have good psychological health.

So again, from your point of view, if you've been through a transplant, you've actually been through a very difficult series of treatments. Your body and psyche have suffered a lot of stress. But you're probably stronger than you think. And if you can adopt healthy living styles, nutrition, exercise and utilize the resources available, you can make a good recovery. And hopefully, the underlying disease is not getting in the way of that.

Ability to Work after Autologous Transplant

38:19     Talked a little about work here, you can go through the slide a bit later by yourself. There certainly are going to be some patients who have physical limitations from the treatment that prevent them doing heavy tasks. And some may have some ongoing chemotherapy effects that may affect optimal thought processing. So those are things that can, again, be worked on. There may be rehabilitation strategies to deal with those.

Family Stressors after Autologous Transplant: Anxiety, PTSD and depression

38:48     Family stresses are an important problem for people who have gone through any form of therapy for serious diseases. They may manifest as a so-called white coat syndrome, in which anxiety and hypertension or high blood pressure is seen, when you visit the doctor but not at home, and blood pressure monitoring can be helpful to resolve that.

That sort of issue figures out what's happening. There may be a need in younger patients for more support, because of this post-traumatic stress syndrome and depression. The more families are involved in the care and recovery, it seems that the more the patients will do well. It's obviously, some level of team activity, transplant, the need for caregivers to be involved.

Some people focus a lot on what we call anniversaries, that is yearly follow-ups. That may be a very strong way to look at it, and that creates the idea of your further down the line, you're winning the battle that you went into. It’s kind of that sometimes needs to be dealt with as a reminder of everything. And so, trying to balance those effects, is an important part of the psychological adaptation, to having gone through this. Nonetheless, what you've been through and your treatment is a part of your past and it's with you. And the question is, how to sort of move on and in really make it count.

Living a Full Life after Autologous Transplant

40:22     And so, I think this is important concept. This issue of trying to make your remission count. You don't really know what the future holds when you've just been through your transplant. You're hoping to be cured or have long responses. Whatever is going to happen, I think one has to try and get over this, as best one can and move forward, and make the most of your life and just look for the day - and... you may not be feeling perfect, but the more positive focus that you can put on this, and the more healthy you can live, and the more you know the better I think you can adjust to having been through this, and move forward and be productive in your life.

Making your health and wellbeing a priority after Autologous Transplant

41:09     So therefore take charge of your health and wellbeing. Preventive care and early interventions in dealing with any sort of problems may, in fact, be very important to your long-term health. Make sure that you're involved in your health, that you understand what communications are taking place between, your healthcare provider and transplant team.

Obviously, in a lot of situations, the transplant team is geographically very removed from where you live, and there may be a geographical barrier. Telemedicine may actually be increasingly important to long this term follow-up of patients as we go forward, and you can use that to your advantage. You can probably do more, with the emphasis on that now, than we've historically done in terms of keeping your transplant team involved in your care. Because you've been through so much, we consider you heroes, from the physician point of view and from the rest of the team's point of view. It's a tough thing to go through. Try and remember that you've been through a lot, that you're strong, you're robust, and you're a hero to your family and friends.

So, just to conclude this talk, we're seeing a lot more people go through transplants. There are a lot more people who are surviving after transplant, and the need is great for this type of follow-up.

We're seeing a lot more people who are older going through their transplants. Post-transplant therapies may improve the treatment.

Preventive health is important for avoiding some problems. You may need to see people who are specialists in these areas, who are not part of the transplant area, particularly if you live far away from a transplant program.

We've talked about regular monitoring and maintenance and trying to avoid complications and then treating them if they develop and treat them early.

And families and patients who are working together seem to do the best. There are resources for you - this is available on the slides you can download - that cover a lot of these issues. Further information you can find at bmtinfonet.org. And now we're going to move to the question phase of the talk today.

43:30     [Moderator] Thank you, Dr. McSweeney. That was an excellent presentation. We are now moving into, like he mentioned, the question phase of the presentation. As a reminder, if you have a question, please type it into the chat box on the lower left-hand corner of your screen.

And it looks like our first question is from Daniel. "You mentioned from your presentation, cumulative toxicity from transplants. Could you say more about that Dr. McSweeney, including its relevance, for a tandem double transplant?"

44:04     [Dr. McSweeney] We know that all of the therapies that we use involve putting chemicals into your system or exposing you to radiation. Those have an effect on the normal tissues, and that builds up over time. And thus, some of the long-term effects of all those treatments that are somewhat nebulous at times and hard to pin down, are probably in a sector of what we call cumulative toxicity.

Now for the tandem transplant, that's an important question. But it's not as well understood as to what the cumulative toxicity during these two high-dose melphalan exposures is. I haven't seen a lot of toxicity reporting. We know what the short-term toxicities are going to be, and they tend to be somewhat reproducible. In some ways, I think the folks who end up doing a second transplant self-select by tolerating the first one well. Now the goal of these tandem transplants, is to try and improve the outcome, obviously, of the myeloma and get a better long-term response to it.

But yeah, and most of the presentations on outcomes after those transplants actually speak to the benefits rather than the sort of the negatives of this. And, I haven't seen really good data that summarizes how much worse it is a year out afterwards, second autologous transplant, than if you just did one.

Autologous transplant for myeloma, I guess I could say one more thing about them. They're not pitched as intensively as transplants are for, lymphoma. And, therefore they're a little bit more tolerable. And that's why we've been able to offer these tandem transplants, because the risks of short term and long-term complications are certainly laced with those transplants, with the inflammatory response.

46:14     [Moderator] The next question: Charles asked, "After nine and a half years after an autologous transplant for non-Hodgkin's lymphoma and in remission, can you say the cancer is cured?"

46:30     [Dr. McSweeney] Well, the odds are very good that it's cured. Now, there are different types of non-Hodgkin's lymphoma. While the more aggressive types of lymphoma, such as diffuse large B-cell lymphoma, are more threatening to an individual, they are actually more likely to be cured in a shorter amount of time than the, what we call the lower grade or follicular type lymphoma. So, if this was a diffuse large B-cell lymphoma, I'd say the odds are extremely high. If this was a low-grade lymphoma, it's a little harder to say that but it's probably pretty good.

47:08     [Moderator] Okay. The next question Michael is wondering, "Can you talk about adverse reaction to rituximab, leading to pulmonary issues?"

47:20     [Dr. McSweeney] Rituximab is a monoclonal antibody which is used to treat lymphomas. It is given, before and after transplant for some disorders. And it's given before transplant for almost all non-Hodgkin's lymphomas. Its major effect on the lungs tends to be what we call infusion reactions. That's the shortness of breath associated with the actual time of the administration. It's not so classically associated with long term damage to the lungs. So, some patients just can't take it because it creates too much reaction at the time of the injection. But the vast majority of patients can take it and take it for long periods of time if necessary.

48:07     [Moderator] Okay. Mitch asked, he's four months out of a stem cell transplant. "I have recently contracted a bad case of shingles on the face. My doctor is putting me on valacyclovir for seven days, two tablets three times a day, 500 milligrams, plus gabapentin, 300 milligrams, one to two times a day. I'm wondering if we should be treating this differently to avoid re occurrence. I've heard that I should be on antiviral medication longer. What are your thoughts?"

48:48     [Dr. McSweeney] Yeah. So, the two comments here is, typically, we would keep patients on their shingles prevention for up to a year after the transplant. And that, for us, the standard is to use acyclovir twice daily for that period of time. I'm wondering if there was no... what happened to the prophylaxis here. The other thing is the gabapentin. It's not a treatment for shingles per se. It's a symptom management. The other question I wouldn't know the answer to here is whether the shingles vaccine was given early after transplant. That some way affected the thinking on the prophylaxis with the acyclovir, or Valtrex is sometimes used as well.

49:39     [Moderator] All right. And there's another question. "How often do you recommend a PET scan after a stem cell transplant?"

49:45     [Dr. McSweeney] Well, it's one of the controversial areas in the field. Now PET scans can be used in both lymphoma and myeloma. We don't use them that often in myeloma, to follow patients because we have other ways of doing that. For most patients that is blood work or protein levels.

For lymphomas, there is no, I think, clear standard. I'm not a big fan myself of frequent monitoring by scans after transplant. There isn't lot of data that it changes the outcome. Anybody going into transplant, who's got disease that's measurable before the transplant, certainly ought to have an initial scan in the first few months after transplant to determine what's happened. And most physicians and patients like to have a little more information in the year that follows. I certainly don't do many scans at all beyond the one-year mark. One year is sort of like an anniversary. The data that says you ought to do a scan at that point, it's not terribly strong. But a lot of people like to kind of get to that point and know where they're at.

50:57     [Moderator] Okay. Tom would like to know, "What indicates full remission in blood work?"

51:04     [Dr. McSweeney] Well, this is would apply to diseases that we could follow by blood. But usually the blood by itself is not the whole answer to assessing remission. It certainly has very little value as a remission test for lymphomas. That might change in the future, actually, as more sophisticated technologies are developed for monitoring, what we call circulating tumor DNA. For myeloma where we do use blood tests a lot, it would be the absence of detectable monoclonal protein from the myeloma, and normalization of the light chains which go along with the myeloma.

51:49     [Moderator] Okay. And Beth asks, "How should a patient advocate for themselves when their transplant team hasn't addressed many of the concerns you've mentioned?"

52:02     [Dr. McSweeney] Well, that is something you could address with your physician. One of the questions that obviously is a little tricky for patients is, when they leave... autologous transplants are relatively short procedures, and you may be at the transplant center for the six weeks or so to do the stem cell collection and then do the transplant, the follow-up, and then you may be moving a hundred, 200 miles away. So how do you continue that interaction? How do you get the most out of that?

52:38     [Dr. McSweeney] Long term follow-up for autologous transplant is probably not as well structured as it is for donor transplants in most centers. And so, it is a little bit of a challenge. I think it's a matter of trying to arm yourself with the information, such as you've got a lot of slides here. You could use those, and you could take them into your doctor, or they could send them in. There are probably other folks who work with your doctor such as the transplant nursing staff and the APPs.

53:07     [Dr. McSweeney] You could use information and present and say, "What do you think about this?" I know that it's a difficult thing to sort of take on with a physician when you think that things should have been done differently, but you can bring those to their attention and also, of course, some of you're going to be working with primary care or oncologist who are not trans planters, and so bringing that stuff directly to them, and using these available resources such as on the websites here, can help you enormously, I think ,in bridging those gaps.

53:39     [Moderator] This will have to be our last question. We're running out of time. On behalf of BMT Infonet, and our partners, I would like to thank Dr. McSweeney for his very helpful remarks. And thank you the audience for your excellent questions.