Presenter: Ernesto Ayala MD, Bone Marrow Transplant and CAR-T Program at Mayo Clinic Florida
This video is a recording a workshop presented at the 2019 Celebrating a Second Chance at Life Survivorship Symposium in Orlando, FL
Presentation is 40 minutes followed by 20 minutes Q&A
Recovering from a bone marrow or stem cell transplant using donor cells requires life-long vigilance to detect potential long-term complications. Having a support team of doctors and family can help ensure a long, healthy life.
- Sixty-six percent of transplant allogeneic transplant survivors develop at least on chronic health condition after transplant, compared to 39% of their healthy siblings
- Long-term complications after transplant can affect nearly every organ or system in the body
- Transplant survivors need to be their own health advocates and work with their transplant team, specialists and local doctors to monitor and protect their health long-term
05:02 Two-third of bone marrow/stem cell transplant survivors report at least one chronic health condition after transplant:
06:01 Risk factors for complications after a transplant using donor cells (allogeneic transplant)
08:25 The incidence of coronary artery disease and cardiomyopathy after transplant is three times higher than the general population
11:45 Approximately one in six patients with chronic graft-versus-host disease will develop bronchiolitis obliterans in their lungs
15:35 25-50% of patients develop iron overload in the liver after a bone marrow/stem cell transplant
19:34 Twenty percent of patients develop kidney problems after a bone marrow/stem cell transplant
23:19 Sexual health problems and infertility in both men and women are common after a bone marrow/stem cell transplant
31:16 Bone marrow/stem cell transplant patients lose all their immunity and need to be re-vaccinated
34:44 Neurocognitive changes or “chemobrain” is common after a bone marrow/stem cell transplant
36:58 How to be your own health advocate
Transcript of Presentation
00:00 Overview of Presentation: Good morning. It is really humbling to be here in front of all of you. The first thing that I wanted to say is I'm grateful to be here and I'm grateful to be talking to you. What I want to do in the next hour is go over how to protect yourself after a transplant using donor cell after an allogeneic graft implantation. But the talk is going to go only for 35 or 40 minutes and from there, all that I want to hear is questions. I'm here to answer questions. I'll do my best to share what I've learned over the years and what I've learned from you. That's what I'm here for.
The name of my talk is Strive to Thrive! How to protect your health after a transplant using donor cells. These are my objectives. I will define what is survival, what is survivorship after transplant. I'm going to describe the most common long-term complications that we see in transplant recipients. I'm going to go over the risk factors for them. How do we screen for these complications? How do we treat them? What you can do to prevent them, and help be on top of this problem to control them and treat them.
01:37 Longest living bone marrow transplant survivor: When I was preparing my talk I bumped into this story. This is Nancy King McLain's story. She is the world's longest living bone marrow transplant survivor. This is a woman that was transplanted from an identical twin for acute leukemia when she was 11 years old. That was in 1963. She is still alive and has a productive, normal life, which is what we all want from you.
02:13 Who is a BMT survivor? This is just a general definition that I found in the National Cancer Institute dictionary. "One who remains alive and continues to function during and after overcoming a serious hardship or, life threatening disease," like you all did. In cancer, a person is considered a survivor from the time of diagnosis until the end of life. For us, it's from the time of having a bone marrow transplant until the end of life. That's the time of being a survivor.
So, a survivor is a person that, after going through disease and then going through a transplant, adjusts to a new normal. There are many, many physical and emotional changes that will happen due to the treatment, due to the disease, due to the transplant itself, and the person will be a new one, like it was described in the previous talk. There will be many changes and there will be a new normal that the patient will have to adapt and grow from there.
The definition of survivor includes anyone else that was surrounding the patient that was impacted by the transplant experience. So, that will include the caregivers, the family members, even the close friends, or any person that was in close relationship with the patient during this experience.
03:44 We have gotten better at doing transplants over the past 20 years: What is the good of an allogeneic transplant? The good of an allogeneic transplant is that as the time goes by, we are learning and we're getting better at it. If you go back 20 years ago, the long-term survival was only 42%. But as the years have gone by, you have seen that the one-year survival for 2010 and 2012 is 63.6, So, about two thirds of the patients become long term survivors, and I think we're getting even better and better as the time goes by.
05:02 Two-third of bone marrow/stem cell transplant survivors report at least one chronic health condition after transplant: What is the bad? Well, two thirds of the bone marrow transplant survivors will report at least one chronic health condition, compared with 39% of their healthy siblings. 79% survivor will have a non-malignant late effect or complication five years after transplantation; and the life expectancy is still lower for transplant survivors compared with the general population, due to some of these medical problems.
As you see here, over time, from the transplant moment, the first two years, the rate of relapse from the primary disease goes down and eventually disappears completely. But then the patient will develop some medical problems that were a consequence of the treatment itself, the transplant, or the disease itself. But you are not alone, So, the number of transplant survivors continues only growing, So, there were about a little over 100,000 BMT survivors in the United States in 2009. But now it is suspected that by the year 2030, there will be half a million bone marrow transplant survivors in the United States.
06:01 What are the risk factor for all the problems and complication that we see after transplant? They all start from pre-transplant medical issues. Many patients, at the time they develop leukemia or lymphoma, they already have coronary artery disease, they have [inaudible 00:06:20] high blood pressures. So, they came with some medical problems already, and then they go through the treatment of the primary malignancy. They are diagnosed, they get chemotherapy, radiation, hormone therapy, all the treatments that we do; and then, eventually, they go to transplant. Then they will have additional intervention. High dose chemotherapy, immunosuppressants, antibiotics. Some of them will develop acute or chronic graft-versus-host disease. Then they will need medications and treatments for that and they will have some consequences. In addition, some of them will have infectious problems or organ injury or other issues will arise.
Now, in all of this, each patient is different. There is the genetic predisposition to certain problems that some patients will have. Some will not develop those problems. There are some problems that will depend on age: older patients that go to transplant tend to have more problems and complications post-transplant. Also, depends on sex: some complication will affect more women than men and depends on the previous lifestyle of the patient.
07:39 Complications after transplant can affect almost every organ in the body: Now, this one looks very complicated, but I just wanted to convey the message that the complication that we see after transplant affect almost every organ or every system in the body. As you see here, patient may develop psychological problems, pulmonary diseases, heart, cardiovascular diseases, stroke, coronary artery disease, kidney injury, iron overload, and I'm going to go over many of these in more detail. But the message is that many organs are affected by the treatments that we use, by the disease, and we see the effects post-transplant.
08:25 The incidence of coronary artery disease and cardiomyopathy after transplant is three times higher than the general population: Let's start from the heart. The two major problems that we see after transplant are coronary artery disease and cardiomyopathy. Cardiomyopathy, I define it here as heart muscle disease, which is essentially weakening of the heart. Coronary artery disease is more common in transplant survivors and starts at an earlier age. Stroke is also more common, and some of the death that we see in bone marrow transplant survivors, up to 10%, come from cardiovascular problems, and that's why this is important.
The incidence, in general, is three times higher than in the general population. Cardiomyopathy, the main risk factor is some of the chemotherapy agents that we use. For example, maybe some of you remember having received something called doxorubicin or adriamycin. This is a medication that could cause some heart damage and weaken your heart.
09:41 Risk factors for heart problems after transplant: Risk factors for heart problems, some of them are independent of the transplant itself, like having high blood pressure, being diabetic, high cholesterol. These happen whether you have the cancer or not or whether you were treated for ... or you had a transplant or not. But some of it will come from the transplant process itself: like if you got total body radiation as part of your transplant, or if you got chest radiation during the treatment of your malignancy. Sometimes we do that in lymphoma.
Chemotherapy agents, I already mentioned anthracycline as a cause of heart injury and weakening of the heart, and there is always some genetic susceptibility. Some of these problems will affect some patients, while others are not affected at all.
10:37 Steps you can take to improve heart health after a bone marrow transplant: What can you do to improve your heart health? These are the most important things. First, lifestyle modification. I'm going to say many times during my talk: stop smoking. If you have even considered it, don't do it. It's going to hurt you, So, I will keep saying that. Low fat diet, maintaining a healthy weight, regular exercise. This is critical. Maintain a good cardiopulmonary function will represent many more years of life.
Diabetes testing, So, your primary doctor will do that. Fasting lipid testing that should start probably a little bit earlier than general patients. Sometimes the doctor will want to do imaging of your heart, like echocardiogram, electrocardiogram, if the doctor is suspecting that the heart is already weak or has problems.
11:45 Lung problems after a bone marrow/stem cell transplant – bronchiolitis obliterans: Let's talk about your lungs. When we talk about the lungs, we essentially have two types of problems. We have non-infectious complications and we have infections. Those are the main problems within the lung. The most important one that I want to mention is bronchiolitis obliterans. This is a word that literally means narrowing of the bronchi, narrowing of the branches of your bronchi. This is a classical manifestation of chronic graft-versus-host disease. About one in every six patients with chronic graft-versus-host disease will develop this serious problem.
How do we know that it's happening? Well, a patient will say that he's feeling short of breath, that it's getting hard to go upstairs or walk for 15 minutes; and then we will screen patients with pulmonary function tests. Many of you have had pulmonary function tests at different time points after transplant, and that's the way we monitor this.
In case that we suspect it's already happening, we're going to do a CAT scan of the chest and look at images of your lungs. We treat this with oral or inhaled steroids and powerful anti-inflammatories like Montelukast but that just the name of the medication.
13:18 Lung problems after a bone marrow/stem cell transplant – pneumonia: The other problem that we frequently see as a lung complication is infection, pneumonia. Pneumonia is common after bone marrow transplantation, and the main risk factor is a compromised immune system. Every patient that goes after a bone marrow transplant will have a compromised immune system for a variable time, 6 to 12 months at least. Then you will be at risk of acquiring lung infection from virus, from bacteria, and very rarely, even from fungi. The main prevention is interaction with your doctor. Your doctor will give you medications to decrease the risk of infection, like prophylactic antibiotics. Many of you probably took an antiviral, an antimicrobial, and an antifungal for several months after transplant.
14:15 Vaccination is important to prevent infection in the lungs: Vaccination: I'm going to go over that in more detail down the road. Vaccination is always important to prevent infection. And while I'm not going to go over the treatment, I wanted to mention this one, antibody replacement. We all have antibodies in the blood. They are proteins that we all carry to fight infection. After transplant, some of the antibodies go low, but we can replace them; and in that way, we can diminish the number of pulmonary infections that a patient will develop.
14:54 What can you do to protect your lungs? First, be vigilant and report any change in your exercise tolerance. If you are doing well and you start noticing that you are getting short of breath easily or if you have a persistent cough, this is a time to talk to your doctor.
Pulmonary functional tests, as I already said, we will do these at certain time points to monitor your pulmonary function. Vaccination, and as I said before, don't smoke, and avoid toxic exposure to fumes or to any environmental exposure.
15:35 25-50% of patients develop iron overload in the liver after a bone marrow/stem cell transplant: Now let's talk a little bit about your liver. Probably the most important problem that we have in the liver is iron overload. Here, to understand iron overload, all of you during the transplant got transfusions, got red cell transfusions. Each time you get a red cell transfusion, those red cells carry a little bit of iron. It's hard for the body to get rid of that excess iron, So, it sits on your organs, particularly in your liver. The more transfusions you get, the more iron you will deposit in your liver, and it comes to a point that it will cause progressive inflammation and damage on your liver. That's the reason why we are very careful about this. About 25 to 50% of all survivors have elevated liver iron concentration, particularly, those of you who had a transplant for acute leukemia, because even before the transplant, you already had many, many red cell transfusions.
So, how do we monitor this? We're going to follow the ferritin. This is a blood test. Each time your doctor sees you in clinic, he's going to ... not every time, but periodically, he will check your ferritin level; and that way we will know how high your iron deposits and we can intervene to make them go down.
How do we treat it? How do we remove iron? There are essentially two ways to do it. Iron chelation: these are medications that we give. It used to be only IV or subcutaneous, but now they come as pills, So, it's easier to do, it's easier to take. These pills, they will grab the iron in your liver and it will go through your urine and in that way slowly but surely, it will go down.
In patients that are fully recovered with normal hemoglobin, we can do phlebotomies. Phlebotomies take one unit of blood from the patient once a month. That is the most efficient and most [inaudible 00:18:05] way of doing it, the one that works best.
18:13 Hepatitis C after a bone marrow/stem cell transplant: Other potential liver problems. Not infrequently, we deal with hepatitis viruses. Some patients, a small number of patients, carry hepatitis B or hepatitis C. Oftentimes, we see them for transplant., tey already have the viruses. Or sometimes they get a transplant from a bone marrow donor who carries the virus and then they will acquire the virus. We need to know these things in advance, and then we will have to use antiviral [drugs] throughout the transplant to protect the patient; because when your immune system is weak, that is when these viruses wake up and grow and cause trouble.
19:01 Other liver problems after a bone marrow/stem cell transplant: Chronic graft-versus-host disease affects the liver, but I'm not going to go over chronic graft-versus-host disease, because there are one or two sessions specifically on that. I would be happy to answer questions, but I'm not going to go in detail on that.
Cirrhosis is the extreme of liver damage. Sometimes we see it. Fortunately, it's rare, but it's the most advanced liver damaged from hepatitis or from toxicity or from iron overload.
19:34 Twenty percent of patients develop kidney problems after a bone marrow/stem cell transplant: What about your kidneys? It's very common in transplant to see patients ... well, not very common, but probably one fifth of the patients will development kidney injury, kidney damage, and they will lose some degree of kidney function. Typically, patients will not feel anything. How are we going to know? Well, each time you go see your doctor, we're going to make sure your creatinine, your BUN ... we're going to see, "Oh, it's going up. Okay, what is happening here?"
20:07 Risk factors for kidney problems after a bone marrow/stem cell transplant: Some of the medications that we use, the immunosuppressants, pretty much all received tacrolimus or cyclosporine to protect you from graft-versus-host disease. These medications put a lot of pressure in your kidneys and in some patients, nothing happens. It's okay. But there is a proportion of patient that will develop some degree of kidney damage from these medications.
Chemotherapy agents. There are a few chemotherapy agents, like platinum, sometimes causes kidney damage.
This one is one that you can control: blood pressure. You guys must be vigilant and monitor your blood pressure and make sure it's always in the right level.
What can you do? As I said, blood pressure control, and report symptoms, although they are usually late when you already develop significant kidney damage. You could develop swelling. Your legs will get very swollen. Everything fluid. You get very weak. Then you really need to let your doctor know. This is also rare, but you could also see some changes in the aspect of the urine.
21:26 Hypothyroidism affects 3-5% of bone marrow/stem cell transplant recipients: Thyroid problems are common after a bone marrow/ transplant, in particular, hypothyroidism, [which will develop in] three to five percent of all the transplant recipients. Older patients tend to become hypothyroid. Radiation to the thyroid or to the necks will typically lead to hypothyroidism, which is lack of production of thyroid hormones. It's more common in women. Even without transplant, it's more common in women to see hypothyroidism.
Symptoms are rare until it's very advanced. We would always monitor thyroids hormone throughout the transplant and after transplant. Fortunately, this is relatively simple to fix. We just need to give hormone replacement in the form of pills and that would suffice to treat this problem.
22:20 Eight to 40% of bone marrow/stem cell transplant patients develop diabetes after transplant: Diabetes. This is probably more important. 8-40% of the patients after transplant will develop or will become diabetic. Why is that? Because some of the medication that we use will put a lot of pressure in your pancreas, like the immunosuppressants. They make you develop intolerance to glucose. Or steroids. Many of you receive steroids for graft-versus-host disease treatment and then steroids will make your blood sugars go up and if you are on steroid for a long time, you may become diabetic.
How do we prevent this? Diet modification and exercise. You will hear this many, many times during this talk. Weight loss and glucose monitoring. Once it happens, well, you will have to see your doctor and get [inaudible 00:23:14] medications for insulin.
23:19 Sexual health problems after a bone marrow/stem cell transplant: Sexual health in men. It is very common to develop hypogonadism, which is essentially low production of sex hormones in men after transplant. It happens in approximately half of the bone marrow transplant survivors. So, these are the most common symptoms: erectile dysfunction, low sexual drive, and we will know because we will find a low testosterone level in the blood and patient will alSo, have general symptoms like fatigue. We would monitor this in all patients and we could always do testosterone replacement in selected cases, to help fix this problem.
In women, it's also, common to have low sex hormone levels after transplant. Many women will develop ovarian failure and early menopause after transplant. In young women, it's common. Symptoms are early menopause, vagina changes, low sexual desire, fatigue, and I forgot to put here, decreased bone density. Your bones will become weak and your cardiovascular risk will also increase when you develop an early menopause.
There is no specific prevention, but we can always use hormone replacement in a very individualized way, because we cannot do hormone replacement on everybody. For example, if there is a history of breast cancer in the family, we're not going to be able to do it.
25:04 Infertility after a bone marrow/stem cell transplant: Fertility. Most of the male transplant recipients will become infertile. They will develop azoospermia. That's the name, but essentially, it's a no or low sperm count. [It occurs in] 70% of bone marrow transplant survivors. [The occurrence] depends on age. Very young patients have a good chance of recovering from this, if they are in their 20s, but older patients will develop this low sperm count. AlSo, depends on chemotherapy intensity. If you go to one of the mild [inaudible 00:25:41] it's very ... the chance that this is going to happen is a lot higher. We will always recommend in young patients or in patients that want to preserve fertility to do sperm banking or more complex techniques, like testicular sperm retrieval.
Same in females, in women. There is alSo, a high, very high incidence of ovarian failure, early menopause, and infertility. Again, it depends on age and chemotherapy intensity. However, we see pregnancies after transplant. We see women that recover menstrual cycles and become pregnant after transplant. But we always say, "Wait a couple of years. We don't want you to get pregnant in the first two or three years. Why? Because that's the time when you are still at risk for relapse with the malignancy and for graft-versus-host disease. We want you to pass that time, and then if you want to pursue a pregnancy, go for it. Okay. We'd always recommend fertility evaluation before transplantation for cryopreservation of oocytes.
27:06 Bone health after a bone marrow/stem cell transplant: Bone health, So, osteopenia or osteoporosis. Many of you had these bone density tests where we look at how hard your bones are. If they are weaker, we will call it osteopenia, but if they are very weak, the most severe osteopenia, we're going to call it osteoporosis; which essentially means your bones become brittle and they are at high risk for fractures. This is very important, and So, it depends on the treatments that you got. In women, the early menopause will be associated with this, and this is one of the strongest risk factors. This extended, prolonged use of steroids like prednisone will make your bones very weak.
Prevention with good calcium and vitamin D intake: this is something that all of you can do and should do. Weight bearing exercises, mobility exercises are critical to preserve your bone health. And, well, we will always ... periodically, we are going to measure your bone density and there are several treatments to make the bones strong again, like some of that I mentioned here, but first one is calcitonin, hormone replacement in women.
28:39 Avascular necrosis after a bone marrow/stem cell transplant: Avascular necrosis. This is more in younger patients. A few do develop this complication. Avascular necrosis is when a segment of your bone doesn't have blood flow and dies, So, that it becomes necrotic because of lack of blood flow. Typically affects the hips more than the knees, and occasionally the ankles and shoulders. The main risk factor is steroid use. Patients who have been on high doses of steroids for extended periods of time. This is up to your doctor to diminish as much as possible your exposure to drugs like prednisone.
Now, the treatment sometimes is conservative. Physically therapy, retraining, but many patients eventually will need a hip replacement or a knee replacement for this type of problem.
29:38 Weak muscles after a bone marrow/stem cell transplant: Myopathy. This is weak muscles. The main risk factor for myopathy are steroids again. Steroids will make your muscles very weak, and lack of physical activity. When you are in a transplant unit, you don't move much, you don't walk much. By the time you are out of the hospital, you already have significant muscle atrophy. Then, if you don't move, you don't exercise, it will get worse. So, here it's critical to limit the use of steroids and to exercise.
30:20 Infection after a bone marrow/stem cell transplant: Infection. All bone marrow transplant survivors have some degree of immune deficiency that is the highest in the first three months. Your immune system is weak. Slowly but surely, it recovers and eventually becomes normal and you can have a normal life; but it's still during those months or even a few years, you are at your high risk for opportunistic infections, viral infections, bacterial infections.
The immunosuppressant medications that you take will weaken your immune system. If you develop chronic graft-versus-host disease, you are going to be at risk for infection.
So, we will always give antimicrobials while in immunosuppression to decrease the risk of infection; and we would always monitor your immune function, measuring your immune cells in the blood, and we will know how you are doing.
31:16 Bone marrow/stem cell transplant patients lose all their immunity and need to be re-vaccinated: Vaccination. This is very, very important. If you remember, once you go to transplant, get high dose chemotherapy, you will lose all the immunity that you had through all those vaccines that you got in childhood. So, you have to be re-vaccinated. Otherwise, you are going to be at risk for all of this.
Not only that, you can transmit it to other people. This is a double problem here. It's personal and it's also social, because you could become a transmitter of the disease. We would always re-vaccinate you for polio, diphtheria, tetanus. I missed putting here pertussis. Hepatitis B, Haemophilus influenzae, pneumococcal pneumonia. This is MMR. Nowadays, you have heard about the measles outbreaks going all over the country due to lack of vaccination. Varicella zoster. And always remember to get your yearly flu vaccine.
32:27 One to 6% of transplant survivors develop a second cancer: Second malignancies. The incidence of a second cancer is higher in transplant recipients and it's about one to six percent at 10 years after bone marrow transplant. These are the most common ones that we will see: mouth cancer, skin cancer, breast cancer, and thyroid cancer. They depend on exposure to certain risk factors. For example, if you got radiation to the chest, like we do for patient with Hodgkin's disease, you going to be at a higher risk for breast cancer.
If you develop chronic graft-versus-host disease effecting your mouth and mouth dryness for a long time, you are going to be at risk for mouth cancer. You aso have higher risk of skin cancer in general after bone marrow transplantation. So, you have to be vigilant of those things.
The risk of leukemia and MDS is only in recipients of autologous transplant, not in donor transplants. We will always recommend you to be up to date with your cancer screening. I'm not going to go over all the table, but I just want to convey the message that you should be up to date in your screening for breast cancer. Get your mammograms on time through your primary care doctor, get your pap smear and human papillomavirus, DNA tests, screening for colorectal. You can do fecal occult blood, sigmoidoscopy, colonoscopy. Your primary care physician will take care of that.
You should also have a routine skin exam once a year. Go to your dermatologist. Have him check your skin. Screening for lung cancer is mostly for smokers. For heavy smokers, they have high resolution CAT scans of the chest periodically. Oral, see your dentist. Your dentist will be the first one to notice an unusual lesion in your mouth, or sometimes you will feel it. "Oh, I'm feeling something new here. What is this?"
Thyroid, this is in the annual physical exam.
34:44 Neurocognitive changes or “chemobrain” after a bone marrow/stem cell transplant: Now a few more things. Neurocognitive and psychosocial. There is alSo, a session on this, So, I'm not going to go in a lot of detail, but essentially, you all have heard about chemo brain. What is chemo brain? Essentially, it's slow brain function. The patient will have problem with short term memories, slow thinking, learning problems, learning impairment, decreased executive function, difficulties to function in daily life.
It happens to some degree to most transplant survivors, but [there is recovery] in almost all of them, for the most part. It's caused by all the treatments or by the transplant experience itself. It declines in the first three month and improves, or is expected to improve, within the next one to five years in most patients.
35:43 Psychological problems after transplant: We also see other things. We see depression. We see post-traumatic stress disorders. When transplant was a very traumatic experience, you will be at risk for PTSD. We'll alSo, see a lot of anxiety in many of our patients.
36:02 Recovery from a bone marrow/transplant will take many months, sometimes years: How to thrive after your transplant. Here it's important to understand that there will be a time of recovery, slowly but surely, recovering from the first few days after transplant until you can say, "Oh, I am back to a normal life or to my new normal life." It will take three months, six months, a year, in which you will progressively get closer to a functioning, productive life.
Active graft-versus-host disease will delay recovery, and that's why it's important to prevent it and treat it on time, and always recognize that you will have a new baseline and you will need to adjust to this new normal.
36:58 How to be your own health advocate: How to act on this. You must be your own health advocate. You need to learn about this, and that's why we are all here, to learn: to learn what to look for, what to expect, what to ask. Ask questions. You have doctors, you have nurses, you have people that have worked on this. Ask them.
Know your treatments or what treatments you got and why you got that treatment. Know what risks are associated with the treatments that you got. Knowledge is power. Your primary care provider will always be essential. He's going to be your first point of contact and the person that will deal with your blood pressure, with your high cholesterol, with your diabetes, with ... it's your first point of contact. You should always be in lifelong transplant follow-up with your transplant doctor.
38:00 Rely on your support team: Now, this is your team. This is your support network, your family. Your family and your caregivers, those that love you, those that care about you. They are your first source of support. Then you have your transplant physician. He will always be there. Sometimes changing institutions, like me, but he will be there. You can always in the appointments, come with a list of question. "Oh, this is happening. What should I do?" Your primary care physician, as I said, he's your first line of help when you have a medical problem. You need to have a good primary care physician.
You will always also, have very [inaudible 00:38:49] primary hematologist. This was the person that discovered you had myeloma, you had lymphoma, you had leukemia, or you had ... So, this is the one that knows you from the blood point of you and will follow you with the transplant physician.
Finally, there will be other specialists that will be involved. For example, you develop vascular necrosis of the hip. Then you will need to see an orthopedic surgeon to have it fixed.
39:19 Resources for bone marrow/stem cell transplant patients: This is your care network, and to finish, some resources that you find, this is one good one. This is transplant guidelines mobile app that you can download from the Apple Store or from Google Play that will list guidelines for patients about the screenings that you need to do, about what to do when you are at six months, at 12 months, at two years. It's different for men or women, So, this is a good resource for you.
40:04 These are some other sources of knowledge here. I think I'm going to finish ... I hope I wasn't too long ... and for now, it's time questions. Thank you very much.
Question and Answer Session
40:20 [moderator] Doctor, thank you very much. Let's hear for Doctor Ayala. That was an excellent, all encompassing, presentation. We're going to take questions now. [Steve's 00:40:33] got a microphone back there, I've got one here. Please raise your hands. We'll try to get to everybody. As I said, try to keep it focused, and I'm sure Doctor will have a few minutes afterwards if you have something specifically to talk about. We're going to start right here.
40:48 [audience] Is it more important to take meds and control GVHD, or get off the meds and let GVHD be somewhat active: Thank you. That was excellent, Dr. Ayala. Thank you very much for volunteering your time to come here today and speak with us. We appreciate it. My question has to do with pulmonary graft-versus-host disease. I'm a long-term survivor, over 20 years, and I still suffer from chronic GVHD of my lungs and throat and nasal passages. I take an immunosuppressant to control it, called mycophenolate. I'm sure you're familiar with it.
My regular transplant doctor has been encouraging me to try to get me off it, So, I try to taper, and I get a cold and I have an immune system response and I end up right back where I started. My question has to do with, I'm skating the edge of the GVHD. In other words, it's present right now. I've got a little cough. I can feel it. I know it's in my lungs and it's impacting me. I cannot fully inflate my lungs, or I'll cough.
So, I'm taking less than a full dose of the immunosuppressant. Is it better for us ... all the people in here ... to skate this edge and allow the GVHD some grip on us, that it exists and is able to flourish at some small level in the body, or is it better for us to push it all the way into the background and take more of the medicine that will push it all the way into the background? I guess if the long term GVHD is causing permanent damage, I just don't know. I'm asking, which is better? Allow the GVHD to exist and take less of the meds or take more of the meds and push it all the way deep into the background?
[Ayala] Yeah. This is one of the most difficult decisions for your doctor, is when to say let's start going down and to say finally stop doing immunosuppression. There are really, not even in the textbooks that we have, specific guidelines on how to do it or when to do it. It becomes like an art.
You want to have the graft-versus-host disease dormant, like at the lowest level possible, hopefully inactive, before you stop the immunosuppression. That's the rule of thumb.
Now, we have sometimes patients that have had graft-versus-host disease for many years, and at some point, you wonder, is the immunosuppressant really helping here? Years. That's hard to answer.
So, in graft-versus-host disease, in many patients becomes dormant and now the patient is not dealing with graft-versus-host disease, but he's just dealing with the damage that it did. You see, and So, then in that situation, stopping the immunosuppression wouldn't be a bad idea. But this is a decision that should be through close collaboration with your transplant doctor.
44:20 [audience] Question about whether a related donor’s stem cells can be stored in case they are needed later by the patient after transplant: Again, thank you very much for being here today. It means a great deal to everyone, including myself. My question is regards to stem cell transplant. My sister was a 100% match and I'm thankful for that. The question that I have: is there any programs available potentially to be able to use her stem cells and to store them for potential future use, if needed?
[Ayala] Yes, there are several programs, but you must be very careful about this. Many of you probably have heard about banking cord blood cells, and there are many public cord blood banks. Sometimes we use cord blood as the source of cells for bone marrow transplantation, but there are companies that are for profit that will do that. The motive that is given at childbirth and they say, "Save your cord blood for your son, in case he needs it in the future." Then you will pay a lot of money to save the cord blood cells for years.
But in reality, the chance that this person, this baby, is going to use those cord blood cells is extremely, extremely low. They will be sleeping in a freezer for life; while if you put them in a public cord blood bank, they will be available for patients everywhere to use when they need them.
So, that's why it's very important ... some of these companies are for profit and they will offer those services, but if you do it in one of ... you donate them to a cord blood bank, they will help patients.
That's for cord blood cells. Adult cells, we rarely, if ever, would save a lot of cells from a donor for future. One exception is- and this is not your case, I think- is in patients with multiple myeloma. Sometimes in multiple myeloma, we save autologous stem cells for a second transplant. But in donor transplants, we don't do that.
47:04 [audience] Question about whether transplant survivors need additional vaccination in light of the measles outbreak: My question is regarding the vaccinations, and, if this current measles epidemic continues, will there potentially be any new thought process on re-vaccinating with the MMR? I know right now, you must be off all your immunosuppressants. Could that potentially change?
[Aylala] That's a very interesting question, and I'll tell you a story. Years ago, there was an epidemic of measles in Brazil. Then, like you said, because this is a live virus, the vaccine is a live virus, we don't want to do it in patients that are still on immunosuppression, because there is a small theoretical risk that the virus, even though it's a weak virus, will grow and cause problems, because you are immunosupressed.
But to try to curb this epidemic in Brazil, they started vaccinating even patients that were in immunosuppressed, and they didn't have problems. It worked. Will it happen here in the States? I doubt it. But potentially, you could do it. I'm not saying do it. I'm just saying there have been some instances in when it has been done.
48:31 [audience] Question about whether donor’s immunity is transferred to transplant patient: I have a short question and then another one, if that's okay. I want to ask, in regards to vaccinations, what she was speaking about, can't they check the titers? Because doesn't that come across with our donors' cells?
[Ayala] No. That's a good point. They don't come with the donor cells. Why is that? Because when you get the marrow from a donor, you get very few cells. They must grow, and they expand many, many, many times. So, even if you had a few immune cells that were reactive to tetanus, they will be very few. They will not protect you, you need to be re-vaccinated.
49:16 [audience] Question about how long risk of infection continues after transplant: Okay. In regards to being immunocompromised, I know that the risk of infection is higher post three months or those first three months. I am still at 15 months out and I am still on the same amount of immunosuppressants that I was once they found the right balance. Does that mean that my risk is still just as high as it was three months post-transplant?
[Ayala] It's not as high as it was in the first three months, even on immunosuppression. Even on immunosuppression. To some degree, your immune system recovers. The highest risk period is the first three months.
However, for as long as you are in immunosuppression, your immune system is not fully functional, So, you must be aware of that.
50:09 [audience] Question about why GVHD comes back after it was under control: I was just wondering, what causes GVH to resurface after it's under control?
[Ayala] That's a difficult question. Over the years, I've seen patients that were on immunosuppression, graft-versus-host disease had become dormant, and sometimes they start going down, and it's sad that you didn't keep the patient in immunosuppression long enough and then as soon as you stop it, boom, it comes back, and you say, "Bummer." So, here we go again. You go back to where you started with the patient back in immunosuppression.
Having said that, sometimes you have a patient that has been off immunosuppression for six months and suddenly develops rash, develop dry mouth, dry eyes. It happened to me just a few weeks ago with a patient that I have.
So, why did it happen? I don't know. I wouldn't be able to tell. But, well, if it happens, we have to deal with it, put it to sleep.
51:21 [audience] In what percent of people does GVHD recur after treatment: That was my question, too. I had graft-versus-host disease ... as you know, because he's my doctor ... he was my doctor ... for three years, and it just suddenly went away. I haven't had any recurrence for over a year now, and that was my question. What percentage of the people will get it back?
[Ayala] That's a very good point. Once it becomes dormant, the longer it stays dormant, the less the chance it will ever come back. If you have been two or three years without it, it will be extremely rare at this point to have it back.
Sort of like the cancer itself.
52:24 [audience] She has a question. Do you speak Spanish?
[Ayala] Yes, I do.
[Audience] I'm going to do the question in English, but if you have more questions, you can talk to her maybe, because she doesn't speak English.
[Ayala] I guess I'm going to answer both ways.
52:42 [audience] Question about when to stop tacrolimus: Yeah, sure. She wants to know ... her husband received tacrolimus, an immunosuppressor, for more than three years. But the level in the blood is very low now, So, they are trying to figure it out it is okay to remove the treatment at all, because maybe it is not working now. I don't know. What do you think about that?
[Ayala] So, really, again, the time to stop ... all patients get tacrolimus or cyclosporine. The time to stop is a clinical decision from the transplant doctor. It depends on many things. Depends you are doing well, you haven't had any problems, you didn't have acute graft-versus-host ... this is the early form. Then your doctor would consider stopping it somewhere around six months after transplant.
There is also a lot of personal variation. Some doctors prefer to keep patients longer on immunosuppressant than others. But in general, you always want, as a goal, to eventually stop immunosuppression on everybody.
Para decirlo en español, es difícil saber cuál es el momento de parar la inmunosupresión. Es una decisión del doctor de transplante que tú tengas. Si tú no has desarollado enfermedad injerto contra huésped aguda, y si tú no has tenido ningún problema hasta ahora, eso le da al médico la posibilidad de parar la inmunosupresion más temprano. Pero si tú ya has tenido enfermedad injerto contra huésped, te va a tocar esperar.
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