Late Effects and Potential Health Issues After a Transplant Using Your Own Cells (Autologous)

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[00:07] Moderator: Welcome to the workshop, Health Issues to Watch For after a Transplant Using Your Own Cells, an Autologous Transplant. My name is Penina Seidman, and I will be your moderator today. 

It is my great pleasure to introduce today's speaker, Dr. John Hill. Dr. Hill is the director of the Allogeneic Bone Marrow Transplant Program at Dartmouth-Hitchcock Medical Center. He is particularly interested in the effective use of cellular immunotherapy - both stem cell transplants and CAR-T cell therapy - to treat patients with various high-risk and relapsed hematological cancers. 

He focuses on minimizing the adverse effects of treatment to optimize functional status and overall quality of life following stem cell transplantation and CAR T-cell therapy. Please join me in welcoming Dr. Hill.

[01:03] Dr. Hill: Thank you, Penina, and thank you to the organizers for inviting me. It's my sincere pleasure to discuss this topic with you today, and welcome to everyone.

[01:19] Overview of Presentation: We will be covering several features of the autologous stem cell transplant process, and we'll begin by discussing what the indications for an autologous stem cell transplant are, when and why we undertake this, and what some of the pre-transplant considerations are in terms of screening and evaluation of patients. 

Then we'll get into the meat of the talk, which is the delayed and long-term effects of autologous stem cell transplant.

We'll also touch upon immunologic issues, primarily infections, and we'll talk about various organ toxicities.

We will then discuss neuropsychiatric and psychosocial issues, sexual issues, and secondary malignancies. All of these issues are central to the quality of life following an autologous stem cell transplant.

And then, of course, I'll be happy to answer questions at the end.

And we'll end on how we, as your providers, and you, as patients, can improve the quality of life and your status after transplant.

[02:35] So, what is an autologous stem cell transplant? 

It's a transplant using your own cells. The cells that we’ll talk about are stem cells. And those are pluripotent cells, meaning they can develop into all the cells of the blood and immune systems.

We screen people, prepare them for transplant, collect those stem cells, condition folks with chemotherapy, and then re-infuse those stem cells. 

The rationale is that in an autologous stem cell transplant, the chemotherapy does the work.  If your cancer is responsive to conventional therapy, which is to say standard doses of chemotherapy, it will very likely be responsive to high doses of chemotherapy. So, if we give high doses of chemotherapy, in many cases, we can greatly impact the response of your disease.

[03:50] Giving high-dose chemotherapy comes with a price because, in so doing, we often will knock out the bone marrow.

But we've devised a workaround for that since we can't avoid it: we collect your stem cells prior to the transplant, freeze them, thaw them, and then give them back after the high-dose chemotherapy. We'll talk about that process a little more over the next few slides.

[04:13] The diseases that are primarily treated with an autologous stem cell transplant are lymphomas and plasma cell disorders. Lymphomas include Hodgkin and non-Hodgkin lymphomas.

There are two instances when we typically treat these patients with an autologous stem cell transplant.

One would be a patient who has very high-risk features at the outset, and we have a sense that it's best to treat them with induction therapy to get them in remission and then take them to this transplant.

But the more likely scenario is someone who has lymphoma receives chemotherapy and enjoys a period of remission. Then, at some later point, they have a recurrence of their disease. They would generally get retreated and then taken to an autologous transplant, which has been very successful in that setting.

[05:07] Multiple myeloma patients may receive either an early or a late autologous stem cell transplant.

Many centers try to take patients to transplant after the initial therapy that they receive. So, someone comes in with a new diagnosis, gets therapy, and we get them into a significantly reduced disease state.  And instead of leaving them in that situation and just waiting for the disease to come back, there’s an opportunity to take them to an autologous stem cell transplant that deepens their response. That puts them in a much better position to enjoy some time off from therapy, sometimes many months, often many years, where they can live their life with a good quality of life before they might need more treatment.

It's not always that simple. Some patients have certain features that suggest that we should put them on maintenance therapy after transplant. Maintenance therapy can be simply a pill, but that's not something that we take lightly. We know that patients like to be off all therapy if possible, but we can certainly do a lot of good to delay the time when we might have to give more aggressive therapy. 

[06:20] Another cancer treated with an autologous transplant is germ cell tumors, specifically testicular cancer. These are tumors that respond quite well when they're in a reduced state after conventional chemotherapy. They can then go to high-dose therapy and autologous stem cell transplant. This gives them the best chance for an extended period of remission. 

In this particular case,  we often do something called a tandem transplant, where someone goes to the first transplant, and then, after recovery, roughly about six weeks later, we take them to a second transplant. It can be quite taxing, but it often succeeds in getting folks into an extended remission.

[07:28] What are some of the pre-transplant considerations?

 We have to screen folks carefully. People are coming to us with all sorts of medical comorbidities, which are other medical problems they have. They also have had various prior treatments, which we need to take into consideration when evaluating them for transplant. We want to prepare our patients as much as possible for a safe journey through transplant.

Sometimes, a person may not be the best candidate for a transplant, and we will discuss with them why they may not be eligible. I will say, though, that in the autologous stem cell transplant setting, those patients are in the minority. Most patients we screen are pretty good candidates for an autologous stem cell transplant, which is much less complicated than an allogeneic stem cell transplant.

[08:46] When screening patients, the first organ we look at is the heart.

We want to see on an echocardiogram that the heart has a good squeeze to it and has adequate function, so that during the transplant, the heart will be able to handle fluid changes and things like that, as well as the anemia that comes along with transplant as a result of the chemotherapy, and other stressors that we see in patients, such as infections and medication side effects.

[09:24] In the same way, we check folks with pulmonary function testing.

For these tests, you breathe into a tube, and you have other tests that essentially assess the ability of the lung to uptake oxygen from the air. That's called diffusion capacity. We look at those tests very carefully.

Someone who has a long-term history of smoking or environmental or industrial exposures may come to transplant with less adequate lung function than someone else. And if there's any question whatsoever, we typically have our lung experts weigh in and do further testing so we're able to hopefully get them cleared for a successful transplant.

[10:19] Many of the chemotherapy agents that folks get during their first treatments to get them into remission before the transplant can have liver effects.

And some folks come to transplant with a moderate alcohol history or with scenarios that have caused them to take a significant amount of Tylenol or other medications that may have had effects on the liver.

All of these things can be important in determining how much liver reserve we have. That means the liver's ability to withstand insults from medications, chemotherapy, infections, and the like while still maintaining adequate function for the patient.

[11:10] The kidneys are also important, and sometimes the chemotherapy agents that folks have had in the past affect the kidneys.

Patients who have longstanding high blood pressure or diabetes may often come to transplant with some compromise to their kidney function, and that's an important thing to realize prior to transplant. That can be a scenario where the transplant may actually lower the kidney function and be a potential barrier to going through the transplant.

Alternatively, if someone goes to transplant with kidney function that's depressed as a result of multiple myeloma involving the kidneys, we can often reverse that kidney dysfunction. We can get those myeloma cells and the proteins out of the kidney with the high-dose chemotherapy before the transplant. So that's a different scenario, and those patients are typically taken to transplant, even though they have some compromised kidney function.

[12:18] Many patients are living longer and healthier, and we now have patients in their 70s and even in their 80s taken to an autologous transplant.

What is more important than age are other medical problems that they have, how many, what type they are, whether they are potential barriers to transplant, as well as the functional status of the patient.

So, if you're someone who has a few medical issues, but you're playing pickleball three times a week, you may be an excellent candidate to undergo an autologous stem cell transplant.

Keeping fit and moving is always good, particularly with a diagnosis of cancer, when it's easy to be bed-bound and not getting up. Movement can help you in terms of your consideration for transplant and getting through a transplant in the best shape.

[13:24] We also screen folks for the availability of friends and family for caregiver support. Caregiver support is a vital part of the transplant process because it's hard to go through a transplant alone. It's really not possible to do so safely.

There are all sorts of situations following a transplant when folks are either too ill or too weak to make rational decisions

They may be at an appointment with us, and we're talking about medications, and it's easy to miss details. And so, having a caregiver as your right-hand person is invaluable. When folks don't have a caregiver, that's a significant barrier to undergoing a transplant. 

Many of our folks who don't have another family member or a loved one that could be their caregiver combine a few friends and have sort of a caregiver committee. That works out fine if those folks are committed to supporting the patient. 

[14:35] The next criterion for being able to have an autologous transplant is the full treatment of active infection.

Going through chemotherapy prior to transplant will make folks neutropenic. That's when your neutrophils, or white blood cells, drop, and you're at risk of infections. We want to make sure that there are no lingering infections present when someone goes to a transplant, because those can become a major issue when the patient’s blood counts are low after the transplant. So that's an important screening process as well. 

[15:08] Finally, an autologous stem cell transplant really works only when you're in remission, or what we call minimal residual disease status. When the cancer is sensitive to chemotherapy and has been reduced to a minimal level, that's when an autologous transplant works best. 

Unfortunately, in instances where the cancer is resistant to all sorts of chemotherapy agents, those patients generally don't make it to a transplant.

[15:43] What are potential sources of cells for an autologous transplant? 

I've already told you that we use pluripotent stem cells, which are the crux of the transplant's benefit. Pluripotent stem cells can develop into all types of blood cells and a new immune system.

For many years, we collected these cells from the bone marrow. That was the only type of transplant that centers did. Every patient would go to the operating room and undergo something called a bone marrow harvest, during which they had multiple bone marrow aspirations collected over a three-hour period under anesthesia. 

Those cells would then be pooled, strained, and processed so they could be delivered to the patient at the bedside a few days later, after their chemotherapy.

More recently, with the advent of what's called growth factors, which are agents that stimulate the bone marrow to produce stem cells and release those stem cells into the peripheral blood, stem cells can now be collected from the bloodstream. This is a more straightforward method. It allows patients to avoid general anesthesia and the risks of bleeding and infection associated with a bone marrow harvest. So, it's really revolutionized the field, and it can be done much more efficiently. 

Generally, patients will receive growth factor injections over a five-day period. At the end of that period, we can monitor specific lab tests to determine whether the cells are ready for collection.

We then place the patient on an apheresis machine, which collects specific cells based on cell-surface markers via an IV in one arm, and returns the remaining cells to the patient via an IV in the other arm.

Those stem cells are then frozen, or “cryopreserved,” at -70 degrees. They're kept like that until the patient is ready to undergo their transplant. They're then thawed and re-infused into the patient. 

[18:11] This is a pictorial representation of the iliac crest, which you may be familiar with if you've had a bone marrow biopsy. This is where the bulk of these blood stem cells are.

We collect the patient's stem cells either by bone marrow harvest or, more recently, by stem cell apheresis, and those cells are frozen.

[18:39] Once patients are cleared for transplant, they're brought into the hospital. Three to six days before the cells are infused, they receive what's called high-dose conditioning therapy.

If you're a multiple myeloma patient, you generally get that therapy on day minus two. And that therapy is designed to kill as many myeloma cells as possible

Then, day minus one, is a day of rest when we let all that chemo wash out of your system.

On day zero, we thaw the stem cells and infuse them into the patient.

If you're a lymphoma patient, it’s likely you’ll have a longer conditioning period, generally starting on day -6. That's also designed to start killing residual lymphoma cells. And then on day minus one, we let all that chemo wash out of your system. On day zero, we re-infuse the stem cells. 

[19:48] The workhorse of an autologous stem cell transplant is the high-dose chemotherapy. The stem cells simply rescue the marrow. The best term to describe the transplant is high-dose therapy with autologous stem cell rescue. That really tells the story of what an autologous stem cell transplant does much better than just saying an autologous stem cell transplant.

[20:21] This is a picture of how straightforward an autologous transplant is. This is a patient from several years ago who gave his permission and was delighted to lend his picture to this presentation.  You can also see one of our transplant nurses holding a syringe containing stem cells. Generally, several syringes containing small portions of stem cells are given over a few minutes. It's very straightforward. 

Stem cells are given through an IV that essentially goes into the chest area to a large vessel, and the stem cells go through that IV. The stem cells go through that IV, circulate in the blood, and home to certain receptors in the bone marrow. It's really amazing.

We don't have to take people to surgery and inject into their marrow or anything like that. This is all very straightforward.

[21:30] So now we're going to transition to the late effects of transplant. 

[21:39] This is from a survey of patients who have undergone an autologous stem cell transplant. They asked patients two questions.

The first question was: How many of these potential side effects were you aware of going into transplant: reduced fertility, chronic fatigue, secondary cancers, cardiovascular disease, hormonal changes, or other? Others tended to include things like GI symptoms, like nausea, vomiting, loss of appetite, cramping, loose stools, muscle aches, and numbness and tingling in the fingertips and toes.

The second question was, how many of these did you actually experience? 

As you can see, with all of these, except for the other category, there was a much greater prevalence of knowledge about a certain problem going into transplant than the patients actually experienced.

So, the take-home message from this is that we're providing this discussion today as an educational tool. And we want to emphasize that knowing about potential complications after transplant doesn’t mean you will actually experience them.

You could even make the point that being educated about these complications could minimize the likelihood that you may experience some of them, because you may be more vigilant in spotting early symptoms that you could bring up with your provider after the transplant and say, " Hey, I know that such and such is possible, and I'm having this symptom. Could you take a look?” And then maybe you get put on a medication that prevents that problem from progressing. 

So the take-home message is that knowledge does not increase risk. It's sort of like if you read the Tylenol insert on a bottle of Tylenol, who would ever take Tylenol? 

So, I want this slide to be reassuring.

That being said, there are potential side effects, and we want to address them and answer your questions. 

[23:52] The post-transplant period is often divided into a couple of different timeframes. 

The first is day zero to day 100, and some people will even divide this further into day zero to 30, and day 30 to 100.,

Day zero to 30 is the period of time that you're actually in the hospital getting your transplant. So, you come in at day -2 or day -6, and you get your cells on day zero.

After you have received your cells, we support folks with transfusions for low blood counts. 

If you have a fever and develop an infection, or even are at risk for developing an infection, we cover you with antibiotics.

We also provide all sorts of supportive medications like anti-nausea medications, anti-diarrheal medications, and things to help you sleep because it can be tough to sleep in the hospital. So, all these things are happening in the first 30 days.

[25:04] The effects of the high-dose chemotherapy you received prior to transplant on rapidly dividing cells are important. 

First and foremost, it affects the cancer, and that's a good thing. That's what we want it to do,  knock down the cancer.

However, it'll also reduce your blood counts. So, if your white blood cell count drops, there's an increased risk of infection. 

If your hemoglobin and red blood cells drop, that's anemia. Those red blood cells carry oxygen to the tissues, so you can get fatigued from that. 

And if platelets drop, they're the cells that help with blood clotting, so you can be at risk of bleeding. And so, all those things are important to follow closely, and we have certain parameters for giving transfusions.

In addition, the hair follicles are affected, and everyone loses their hair, but that’s temporary. We recognize that hair loss is very difficult for some folks because their hair can be really important to them. We encourage folks to seek out support with kerchiefs, wigs, ball caps, and whatever needs to be done to get through that period. Everybody's hair grows back. 

We have mucosal cells in our mouth, the smooth cells that coat our mouth, and those cells can slough off. You can develop mouth sores, called mucositis. 

Infections, I've already addressed. When the white blood cell count is low, folks are at risk for bacterial, fungal, and viral infections. In this early period, bacterial and fungal infections are a greater risk than viral infections, which tend to occur a bit later. 

The other thing that can happen with high-dose therapy is that you can get leakiness of your endothelial cell junctions. That's the distance between cells in your body that prevents fluid overload in your lungs, heart, and other organs. That can become a little bit compromised. So we have to be very careful about how much fluid we give people.

So, we check weights daily to make sure no one's gaining more weight than they should. We try to keep people's weight at a stable level. Using Lasix to make people urinate and keep their weight stable is very common.

The last three items that I have on this slide are relatively low risk, and they're much less of a risk than with an allogeneic stem cell transplant. But they do come up if you're reading about autologous stem cell transplants, and occasionally when folks are going through a transplant. 

Sinusoidal obstruction syndrome is a toxicity of chemotherapy to the liver, and it's characterized by weight gain, enlargement of the liver, which can be tender, and a rise in your bilirubin, which can cause jaundice. In the worst-case scenario, it can compromise liver function. In most cases, it either doesn't occur or occurs in a very self-limited way, and we're able to recognize it and support people through it.

It tends to be based on small clots that form in the central part of the liver, which then increase pressure in the liver and ultimately lead to fibrosis. So, we watch this very closely.

Another side effect called idiopathic pneumonia syndrome is also uncommon. It occurs in the 30 to 100-day time frame. This syndrome, which we call IPS, generally occurs after folks are discharged from the hospital,. They notice a little bit of breathlessness, maybe a low-grade fever, and a mild, nonproductive cough. They get a little bit winded when walking, and they come in and they tell us, you know, something just seems a little bit off.

So, we check for this and treat it with immunosuppressive medications, steroids, and a drug called Etanercept, and we are very aggressive about following patients to make sure it turns around.

The next problem is CMV (cytomegalovirus) reactivation, which is much more of a risk in the allogeneic stem cell transplant setting than in the autologous transplant setting. But occasionally folks do monitor this after an auto transplant, and we want to make sure that it doesn't reactivate and cause pneumonitis, which is an infection in the lung that can be serious, or involvement of the liver or the bowel. So we watch for this, and generally it doesn't occur, but we're vigilant to make sure it doesn't.

[30:25] This is a pictorial representation of some of these side effects: the mouth sores, bleeding, bacterial and fungal infections, and kidney issues. These can happen when you're in the hospital during your transplant.

Some of these other things are a bit later in the day, 30 to 100 time frames. And you can see I  have shingles on here as a later side effect.

Viral infections are more common in the latter stages. I wouldn't say they're common, because we do protect people with medications like acyclovir that help minimize the risk of these infections.

[31:09] Then there are the late complications that we'll talk about. These tend to relate to the immune system's ability to recover after a transplant.

We're essentially knocking out your immune system and replacing it with the same one over time. The chemotherapy knocks out the bone marrow in the immune system, and then the pluripotent stem cells that we re-infuse on day zero will ultimately develop into a new immune system, but it doesn't happen immediately. It takes about six months for this to happen. So,  that's what we call immune reconstitution, the process by which all of your immune elements settle back in after an autologous transplant, and that takes about six months.

During that timeframe, you're at risk for not only bacterial and fungal infections, but viral infections as well. The risk of these generally is up to about 200 days. At that point. Most patients are over a significant risk of infection.

But there may be some other, more functional issues, like energy. But the high infection risk is over, unless someone, for whatever reason, remains on steroids and is immunocompromised further.

[32:40] The lung disease that we talked about can be caused by an infection, or it could be inflammatory. The inflammatory type is related to post-chemotherapy toxicities.

Some of the chemotherapy agents that we use have toxic effects on the lungs. That goes back to why we screen people so closely before taking them to transplant. We have to prepare for the possibility that someone may develop a lung infection or another process affecting the lungs, such as inflammation due to chemotoxicity. We're still able to get them through this because their lungs have enough reserve.

[33:27] Then we look at quality of life issues, which can extend beyond the day 100 to 200 timeframe and be more chronic issues. 

Chronic fatigue, difficulty getting up and moving, stress, and anxiety. After folks have recovered from the transplant, they wonder what's going to happen now? I've done my transplant. Now, what do I do, just waiting for the other shoe to drop?

We tell people that with every passing day you're in remission, are doing well, and don't have disease, the likelihood that you're going to remain that way increases. So, hopefully that's more of a self-fulfilling positive feeling as you get further out from transplant.

And then there are the issues with infertility. We knocked out the germ cells because they are among the rapidly dividing cells affected by chemotherapy.

There are issues with intimacy, self-esteem, some cognitive and thought process changes, concern about the potential for relapse, and the risk for secondary cancers, which we'll address on other slides to come. 

[34:47] This is the pictorial representation of what life is like after day 100 up to a couple of years after transplant. Essentially, people are back on their feet and may or may not have some chronic issues to deal with, like respiratory infections. 

You can certainly see bacterial infections, but often there are viral infections, and we know that every winter our patients get the same infections as everyone else. So, even if your immune system has recovered and you're not so prone to getting infections, you can still be prone to getting influenza, COVID, and all those things that the rest of the community is at risk for. 

There are encapsulated bacterial infections. We don't generally vaccinate folks after an autologous transplant, although some centers do. And this is one of the foci we look at: vaccinating folks against encapsulated bacteria, such as pneumococcal pneumonia. 

And then there are rarer infections, like Pneumocystis carinii pneumonia. And so, we prophylax against that for the full six months after transplant, since that's the period of time it takes for immune reconstitution.

Some of the risk factors for late infection include extensive pre-transplant therapy before you even come to the transplant center. Your immune system may be more beat up. Yet, patients generally do well, and if you're able to collect stem cells for your transplant, that suggests that you've got enough reserve. 

Some of the chemotherapy agents used for conditioning prior to autologous transplant may increase a patient’s risk for infections.  And total body irradiation (TBI), which we don't use much for autologous transplants, can also compromise the immune system.

 And prolonged immune suppression. This gets back to the immune reconstitution issue. 

Another issue we talk about is a drop in your gamma globulin level. Gamma globulin is the immunoglobulin G that we primarily look at. Those are the antibodies that your immune system makes to fight bacteria, fungi, and viruses. . After transplant, the gamma globulin level can be low.  So, we follow those numbers and give people intravenous immunoglobulin (IVIG )to get those numbers back up. So, there's a lot that we can do to continue to beef up your immune system and minimize risk for infection. 

[38:14] What about the prevention and management of late infections? 

Depending on the scenario, we often give antiviral prophylaxis with acyclovir. People generally remain on acyclovir medication for six months after their autologous transplant, and that goes a long way towards preventing shingles reactivation, and other viruses. 

Revaccinating patients against pathogens is not always done after an autologous transplant. It's always done after an allogeneic transplant, but this is a center-specific practice. At our center, we generally don’t revaccinate patients and they have done quite well. 

And then, of course, monitoring is one of the best mechanisms for prevention and management of infections. Prevent it, and then it never arises. 

There's a low threshold for testing. So, if a patient comes in and has minor symptoms, we typically test. We're much more apt to detect something early and jump on it quickly. 

So, it's always appropriate to reach out to your transplant team. If you have a minor symptom, it's never wrong to call your transplant provider and say, “Hey, I've got the sniffles. What do you think?” And often, by testing at that point, you can detect something early that can be treated with antibiotics or antivirals.

[39:51] So we're going to now look at organ-specific issues after an autologous transplant.

[39:58] From a cardiovascular standpoint, you can see that these problems are relatively low, but still, that can be significant for someone. Certainly, we don't want to have any life-threatening complications, and we don't want to have any cardiac complications that minimize someone's ability to be active and vibrant in their post-transplant scenario. The whole goal here is to effectively treat the cancer and also leave folks with a good functional status that allows them to live their lives. And our patients constantly remind us, " Hey, doc, if I can't feel well, what's the point of this? 

And it's a wonderful thing that they remind us of this, and we get it. We really want to maximize your functional status and your quality of life.

[40:43] Cardiovascular problems are often due to high-dose chemotherapy. One of the medicines that can compromise the heart is cyclophosphamide. The toxicities can range from dysrhythmias, like atrial fibrillation, to heart failure, where the squeeze of the heart is affected , or pericardial effusion, where there's fluid around the heart due to infection, bleeding, or inflammation.

[41:28] We have to remember that patients going through transplant are normal folks who would have potentially been at risk for coronary artery disease, just like everybody else, depending on family history, lifestyle, and all that sort of thing.

[41:48] But that's one of the reasons why we prescreen. If we find someone who is at risk for coronary artery disease or is having symptoms that concern us, that's generally something we try to address before the transplant, so that we don't get in the middle of transplant and then have heart attacks and things like that. In general, when we screen, if there's any question, we refer to our cardiology consultants and get the issue resolved before they come to the transplant theater.

[42:18] Cyclophosphamide’s effects on the heart are often reversible. They can be pretty significant, but in general, the heart recovers from them, whereas some other chemo agents are more difficult for the heart to fully recover from. 

[42:43] Other late complications include inflammation and metabolic changes called metabolic syndrome, which is characterized by weight gain.

[42:56] Obesity, insulin resistance, diabetes, high cholesterol, those sorts of things can increase your risk for heart attack and stroke, more so than if you hadn't undergone a transplant.

So it's very important that after the transplant, you're watching all of your general medical health issues and get regular screenings, particularly as folks get further out from transplant and are doing well and recovering. We want you to remember and undergo, with your primary care provider,the general health screening measures that are important for everybody.

[43:40] Well, what are some of the risk factors for these cardiac toxicities?

Age, prior medications that might have been toxic to the heart, diabetes, which can have long-term effects on the heart, and prior radiation.

Often that's something that comes up in the Hodgkin's disease or non-Hodgkin's, the lymphoma patients.

[44:05] How do you minimize cardiac risk?

Well, really it's lifestyle and prevention. This will be a common theme even at the end when we talk about how to optimize recovery after transplant.

So remain active, do your steps. You don't have to run a marathon to try to minimize your risk factors. Just walking can be helpful. Just moving.

Studies now show that simply standing at work instead of sitting can be very helpful. But getting those steps in is really helpful.

Try to embrace the Mediterranean diet. So lean meats and vegetables more than red meats, avoiding fried foods, eating fruits and vegetables, using extra virgin olive oil, all that sort of stuff.

And then compliance and follow-up. Taking your medications as prescribed is very important to keep your blood pressure under control.

Check your blood pressure at home and keep in touch with your provider. All these things can be important in minimizing cardiac risk after transplant.

[45:20] What about lung toxicities? Lung toxicities affect 40 to 60 percent of patients, and are higher for folks who have a history of smoking or some radiation.

Inflammation, infection, or bleeding can affect the lungs and are often linked to the conditioning therapy. These can be worsened by low blood counts, particularly platelets, that increases your risk of bleeding in the lungs, or anemia, which may make you more short of breath with minimal activity. We can fix those with transfusional support and staying on top of these things.

Bacterial and fungal pneumonias can occur early or late. We've talked about the idiopathic pneumonia syndrome. We've talked about pulmonary toxicities that can be related to inflammation that, in some cases, cause fibrosis and interstitial pneumonia, which is the IPS and CMV pneumonitis.

There's also a pneumonia called cryptogenic organizing pneumonia that folks can develop around day 100 and thereafter, and that's very sensitive to steroids, very responsive to steroid treatment. So that's an important one that we look for because it is so responsive to treatment, and we can turn it around quite quickly.

[46:43]Then there are the kidney effects. This can be related to chemo conditioning, both before transplant and also the high-dose therapy that comes with the transplant. If you've had infections, and particularly infections that have been severe, leading to sepsis, which is when the blood pressure drops, if the blood flow to the kidneys is reduced, then the kidneys can go a few minutes without the optimal blood flow, and part of the kidney can be compromised.

There are also many drugs that can be toxic to the kidneys.

Veno-occlusive disease or sinusoidal obstruction syndrome caused by the chemo effect can lead to weight gain, a tender, enlarged liver, and bilirubin elevation, and can also affect the kidneys in some circumstances. 

Most patients who have their kidneys compromised after a transplant do not require dialysis. The kidneys are pretty robust, and they can take a lot of compromise and still do their job. So having a little bit of kidney dysfunction does not necessarily prevent folks from coming to transplant, but we have to be aware of why that is true. Particularly in myeloma patients. Those are good candidates because we think we can improve them coming into transplant.

[48:33]Older age, pre-transplant issues, and high-dose therapy can affect the liver.

The better the health of your organs when you come to transplant, the less likely you are to have toxicities.

[48:55]From a hormonal standpoint, you can also have effects on the thyroid and other glands, such as the adrenal gland, due to conditioning and some of the medications that we use. In particular, high-dose steroids or long-term steroids render the adrenal gland less functional. We have to take that into consideration when we're tapering steroids.

[48:23]Gonadal failure. Many of our patients have had families after transplant. If you don't want to have a family after transplant, use appropriate measures because many folks will still maintain fertility even after a transplant.

[49:58] Metabolic syndrome, insulin resistance, lipid issues, and thinning of the bones, can occur after transplant.

Orthopedic issues, mostly osteoporosis, can occur after transplant. This occurs particularly in myeloma patients, who are already at risk for bone thinning from the natural history of the disease. Also, folks who are getting steroids will be at risk.

Vitamin D deficiency is very common in our patients, and we check for it and replete it.

Many patients with prolonged bed rest and inactivity will become deconditioned. So, we have to get people up and moving, and we recommend that all of our patients coming back after transplant keep moving and begin exercise and mobility.

There is something called avascular necrosis, which is the death of some of the bone, generally in the hips and some of the other joints, often after prolonged steroids. Those patients may or may not need hip replacement and other joint replacement, but they do pretty well after replacement. Some folks still maintain their mobility despite having some avascular necrosis.

And then, of course, vertebral compression fractures can be an issue, particularly in our myeloma patients. DEXA scans are often recommended in the 6- to 12-month timeframe after autologous transplant with regular follow-up.

[51:13] How do you prevent osteoporosis?

Well, we monitor for osteoporosis with DEXA scans. We check vitamin D levels, and we give calcium, vitamin D, magnesium, and supplementation, encourage exercise, and give hormone replacement therapy to certain patients, depending on the circumstances. 

[51:42] Neurologic toxicities. In the short term, early after their high-dose therapy, folks may have confusion or seizures related directly to the conditioning.

There can also be bleeding related to the low platelets or high blood pressure at the same time, or patients can fall. These are really important issues to consider. We make sure that our patients aren't walking around if they're lightheaded, that we maintain their platelets at a safe level, and that we minimize risk for these kinds of things. 

And then a bit later, the issues of peripheral neuropathy, numbness, and tingling can occur. Certain medications can put you at risk for that. And some patients will develop a tremor, although most patients do not. 

There's a very rare complication called PRES that can affect thinking and brain function. It’s generally related to high blood pressure, and if we relieve that, we can often treat this and turn it around quickly. 

[52:36]Cognitive challenges. Many folks have heard of the term chemo brain or brain fog, which is common after regular-dose chemotherapy, but also after high-dose chemotherapy. It's usually temporary, resolving in a few weeks, but some patients may have more prolonged effects, and memory issues are common. These are all things that come with aging anyway,  and it may be a little bit accelerated after a transplant. 

Contributors can be things like fatigue, poor sleep, dehydration, infection, nutritional compromise, anxiety, and depression. Our management strategies are individualized, depending on what we think the basis is. But that's very important because it really affects quality of life, which is really the be-all and end-all. 

[53:34] Depression and anxiety. I don't need to tell any patient with cancer that depression and anxiety can be an issue. Fear of relapse and financial stressors, loss of identity, relationship issues, all of those are very, very common. 

As physicians and nurses, we have to remember to bring those up in a thoughtful way and make the patient and caregiver really understand that we care deeply and we want to hear what's going on with them. 

Some patients will even manifest PTSD after their transplant experience, but it's our goal to support them through the transplant, so they won't have those kinds of experiences.

Protective isolation to avoid infection can promote loneliness, and an inability to resume social contacts could be an issue.

[54:19] The physical and emotional distress can cause inability to sleep and chronic fatigue, and sexual issues that can impact relationships and a sense of well-being and physical recovery. 

So why sexual issues? Some of them are emotional. Some are more related to things like physical effects, vaginal dryness, atrophy, and in men, erectile dysfunction. These are very real issues and are important because they're central to the quality of life.

Patients with  decreased libido often say, “I don't have the energy. I just don't think about that. I know that's not something that I can even think about anymore.”

These are important, though, and I'm listing them here because we want our patients to come in and talk about them so we can help them. If we don't know that they're occurring, then we can't help. But it's also our job to ask about these things in a thoughtful, supportive way, not in the last five minutes of the appointment.

[55:32] Premature menopause can be brought on by the high-dose therapy. There are many different ways of managing this.

The important message is these are recognized, they're important issues for our patients, and we want to be there for you to make sure that people are given the support that they need.

[56:00] Secondary cancers are an issue of concern to patients. What I want to emphasize here is that these cancers are often easy to screen for and closely watched. 

So, for instance, we follow blood counts in the first years after transplant. Secondary myelodysplastic syndrome and leukemias can be an issue, and we monitor for those. 

In the solid tumor realm, you can see that breast, colon, skin, and oral cancers are the main topics, and yet those are quite easy to screen for. Regular mammograms, colonoscopies, dermatologic appointments, and dental appointments are all quite important, and you can screen for these fairly easily. 

They're more common as you get further out after transplant, not so much in the early timeframe. And the risk factors tend to be prior chemotherapy or radiation, older age at the time of transplant, and then if there's been smoking or other environmental exposures. So these are lifelong screenings and checks needed.

And then there are various benefits. If you're screening for these, then you're going to more optimally manage treatment-related toxicities. You're going to be aware of early relapse, potentially, because we're looking at folks more closely. and just preventative practices in general. And this promotes favorable long-term health and well-being. 

[57:43] So, as physicians and nurses, what can we do to help improve quality of life? 

We have to have compassion and inquire. We must ask how patients are doing. We have to consider pharmacologic interventions when we can help things that way, and we have to be willing to take patients off medications when they're not helping, and patients are tired of taking too many meds. 

Psychosocial support is paramount to both the patient and the caregiver.  Peer groups are really helpful, often in our adolescent and young adults, and our older age groups. Everyone benefits from survivorship assistance.

Occupational physical therapy for folks who would benefit and OBGYN endocrine assessment for sexual issues, particularly in our women.

And then caregiver assessment, we have to support our caregivers. They're a vital part of the transplant process. And the better supported the caregiver is, the better the patient will do.

[58:51] What can patients do to improve their quality of life?

Staying active. Sometimes it's easy for us to say that you don't necessarily feel like being active, but just moving is important. It doesn't have to be running. It doesn't have to be intense physical activity, but moving around, walking, doing your steps, a nutritional diet, infection prevention by hand-washing, wearing masks, avoiding crowds, and things like that, at least in the short term.

Embrace your follow-up visits, sharing symptoms and questions so we know what's happening.

Seek support from family and friends. Social contacts are very, very important, [so that's really helpful.

Manage cognitive changes. It's easy for us to say, be patient with brain fog, but it does generally get better.

Listen to your body. If you are fatigued or have anxiety or depression, reach out for help because there's a lot that we can do. 

Gradual socialization. We want to get you back to life and to the identity you had before transplant.

Re-engage with your employer, go back to work, if that's possible. It generally is, and patients often thrive in this scenario.

So strive to recapture your identity and find purpose. 

[1:00:11] And then our conclusion slide.

Autologous stem cell transplant remains a highly beneficial treatment for many patients. It's well tolerated and can, in many instances, achieve lasting remissions.

Autologous transplant tends to avoid the long-term immunologic issues that are caused by allogeneic transplant, [transplant with donor cells]  so it's a simpler process. 

There needs to be ongoing efforts to minimize infection and toxicity from the conditioning regimens.

Health maintenance is increasingly important, as patients live longer and strive to regain quality of life.

This increased emphasis on quality of life and survivorship is central to the success of this modality.

And we can't forget about our caregivers. They have to be thriving and surviving just like our cancer patients; that's our goal moving forward.

[01:01:07] And then in the final slide, this is an example of a survivorship effort. These are all cancer survivors rowing in Hanover, New Hampshire. 

Our transplant nurse practitioner came up with this idea and put it out there., and the patients literally came flocking to the sign-up sheet.

So many people are involved in this now. It gives them a purpose. They feel great after the exercise. And these are people who had no experience in rowing, but they're out there on the water almost daily, and it's been a great focus for them.

But the important thing is to find something you're interested in, feel good doing, and that gives you a sense of exhilaration. That can be a key to getting back on your feet.

[01:02:07] Thank you very much. I'm happy to take questions, of course.

[01:02:11] Moderator: Thank you so, so much, Dr. Hill. I couldn't say it any better than what is already in the chat, saying how great this presentation is.

“ My family and I are watching Dr. Hill together. Very informative. So, thank you for that.

We went a bit overtime,  so we only have time for two questions, and I want to address questions that were not included in your presentation.

[01:02:34] So one question that came up a couple of times is the presence of GI, gastrointestinal issues, or digestion issues following transplant, and if there's any information about that or advice.

Dr. Hill:  Sure. Well, that can be a widely variable issue. Some of that can relate to preexisting issues going into transplant, such as irritable bowel syndrome or inflammatory bowel. I

In many cases, we have many modalities that can help folks get back on track. We do use our GI consultants readily because that's their area of expertise.

And so, yes, we see it. Some of them are temporary. Things like nausea are often chemo-related and more of a temporary issue. But we certainly see long-term problems as well.

By knowing as much as possible from our patients, we would then get them plugged in with our GI specialists and work together with those folks to try to address those problems, whether it's something called gastroparesis, where the GI tract isn't moving, or chronic diarrhea, things like that.

There's often a lot we can do to minimize and resolve those effects.

[1:04:04] Moderator: What are some questions that you think a patient should ask their medical team when they're experiencing different symptoms? We're being asked for advice on how to go into an appointment and what questions to ask when they're experiencing different types of symptoms.

[01:04:17] Dr. Hill: If you're experiencing symptoms and it's not near the time of an appointment, don't wait. All transplant programs have points of contact. Reach out to your point of contact when you have a symptom that's troubling you and are uncertain about what to do. 

No question is a dumb question. If you reach out and say,” I'm having this symptom,” you'll either be reassured or you may be told, “We think you should come in a little bit early, and we should have it checked out.” The intermediate answer would be: “Let's see how it goes over the next few days.”

But by asking early, we get a sense of what may be going on that we can address before it becomes more significant.

Any symptom is important if it's a change from your baseline, is uncomfortable for you, or is getting in the way of your quality of life. It's never wrong to ask about those, whether you're in the office or out, or when making a phone call.

 [01:05:39] Moderator: If someone who had received an autologous transplant years ago were to relapse, would they be treated the same way, or would there be consideration of other modalities, such as CAR-T cell therapy?

[01:05:54] Dr. Hill: That's an excellent question. And the answer is often it's a different modality.

Some patients will be candidates for a second autologous transplant. A lot depends on how long their response was after the first transplant. If it was a very robust response, it may make sense to give them a second transplant and get another few years out of that one. 

Other modalities have emerged, such as CAR T-cell therapy, which are excellent therapies, and, for many patients, it will be more appropriate to pursue an alternative therapy, such as CAR T-cell therapy or BiTE therapy. 

There are certain issues that will pop up when an allogeneic stem cell transplant is appropriate for someone who has relapsed after an autologous transplant. 

It depends on the disease and the situation at hand, but nothing's off the table. All of those are reasonable considerations, and we have so much more to offer our patients these days. 

[01:07:04] Moderator: That was a great question. Thank you so much. This has been an incredible, very, very thorough, very informative presentation. On behalf of BMT InfoNet and all of our partners, I want to thank Dr. Hill for this session and the audience.

[01:07:27] Dr. Hill:  My pleasure.