Safeguard Your Health from Late Complications after a Transplant Using Your Own Cells (Autologous Transplant)

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Safeguard Your Health from Late Complications after a Transplant Using Your Own Cells (Autologous Transplant)

Saturday, April 30, 2022

Presenter: Jana Reynolds MD

Presentation is 38 minutes long with 19 minutes of Q & A.

Summary: Autologous transplants (using the patient’s own cells) are typically done for myeloma or lymphoma. This presentation reviews the potential complications that may arise from this procedure and provides numerous recommendations for how they can be managed or avoided.

Highlights:

• Radiation and anthracycline chemotherapy can elevate risks to the heart although better radiation techniques are now used and maintaining overall heart health can mitigate these risks.
• Early recovery refers to the first 100 days when transplant toxicities and infections are treated. Late recovery occurs after 100 days as physical recovery outside the hospital proceeds. Emotional recovery often doesn’t happen till after chemotherapy and transplant.
• The good news is that most autologous transplant patients can return to a similar level of functions then go back to work and activity. Maintaining overall good health with appropriate screenings and preventive measures can maximize quality of life.

Key Points:

(04:25): Transplants may be done to attempt a cure, achieve a remission, or lengthen and improve quality life.

(08:21): Patients are at risk of infection in the first year after transplant, with an increased risk of bacterial infection in the first 30 days. Viral infection risks continue through the first year of recovery.

(11:14): Guidelines for all recommended vaccines should be carefully followed.

(14:02): Lung toxicity can arise from both chemotherapy and radiation and may be treated with steroids.

(18:06): Neurologic toxicities may also arise along with chemo brain which can affect higher level functioning but usually improves with time.

(22:23): Bone thinning is not common but weight bearing exercise or certain medications to strengthen bones can be helpful.

(24:05): Hormone deficiencies can impair fertility or sexual function and women may experience hormone imbalances that mimic menopause but can be treated with topical or oral hormones.

(29:17): Having a complete blood count at least once a year is recommended.

(30:42): Fatigue is common for transplant recipients, but prolonged fatigue should be examined for other causes.

(33:42): Scanxiety and fears about cancer returning can pose mental health challenges. Depression and anxiety are also more common in cancer survivors but can be treated with counseling and medication.

Transcript of Presentation:

(00:01): [Michala O'Brien]    Introduction. Hello, my name is Michala O'Brien. Welcome to the workshop, Safeguard your Health From Late Complications after a Transplant Using Your Own Cells.

(00:11): It's my pleasure to introduce Dr. Jana Reynolds. Dr. Jana Reynolds is the Associate Medical Director for the Blood and Marrow Transplant Services at the Texas Oncology-Baylor Sammons Cancer Center. Her clinical focus is autologous and allogeneic bone marrow transplantation. She's an active investigator on multiple clinical trials and developed a special interest in post-term treatment survivorship care following her own stem cell transplant. Her interest include cancer survivorship education, late effects of treatment, management of psychosocial issues, and exercise and lifestyle modification. Please join me today in welcoming Dr. Reynolds.

(01:00): [Dr. Jana Reynolds]    Overview of Talk.  Thank you. It's an honor to be here with you today. I'd like to thank the BMT InfoNet for hosting this survivorship symposium. Today, I'll discuss the late effects of autologous transplant. My talk link provides an overview of auto transplant, reviews late complications of auto transplant, and discusses steps that you can take to protect your health.

(01:29): Transplants have increased over the years with improved safety and become available to older patients as well. All right, first, a little background. This is a graph of all transplants in the United States from 1980 to 2019. The green highlights autologous transplants, and the blue highlights allogeneic or donor transplants. You can see both curves going up with time increasing from 1980 to 2019, with over 14,000 people undergoing autologous in 2019. One of the reasons for the increased use of transplant is improvement in safety over time.

(02:06): This is a graph of recipients' age for autologous transplants year by year from 2000 to 2019. If you'll look at the blue box, that represents ages 65 and older. We can see that in 2000, only 11% of transplants were done for 65 and up, and in 2019, 36%. That's based on the improvement in technology over time and safety of transplant.

(02:44): Autologous transplants are typically done for myeloma or lymphoma. The most common reason for transplant, autologous transplant, specifically, is myeloma or lymphoma. This is a graph of all transplants in the United States in 2019. The green highlights autologous transplants, which we'll focus on today. Myeloma or plasma cell disorder, for example, amyloidosis, is the most common. Non-Hodgkin lymphomas are the next most common. Hodgkin lymphoma listed here as HD or Hodgkin disease is also transplanted occasionally. And then there's a smaller category called other malignancy. This represents a small subset of solid tumors in which we do recommend autologous transplant, the most common being testicular.

(03:31): This is a visual representation of a hematopoietic stem cell. In the middle, you can see the stem cell. These stem cells live in the bone marrow and their job is to make blood cells -, red cells, white cells, and platelets. These blood cells die off and it's up to the stem cells to make more.

(03:56): Autologous transplants use the patient’s own stem cells. I think of the stem cells as workers in a factory, that is the bone marrow, that makes the blood cells. In autologous transplant, when you use your own cells, the cells are actually supportive. They help you get through the treatment safely. The actual treatment is high dose chemotherapy and occasionally radiation, which treats the cancer. The stem cells help keep you safe by helping you recover faster.

(04:25): Transplants may be done to attempt a cure, achieve remission, or lengthen and improve quality life. The goal of transplant varies for some. For all, it would be to help you live longer. And for some, it may be to cure your disease and keep it away forever. For others, it may be to put your disease in remission for as long as possible, but importantly, we also want you to live well, have quality and

(04:55): High dose chemotherapy is used to minimize cancer cells in the body as much as possible. This is an example of the steps required to undergo transplant which many of you are, likely, familiar with. We start at diagnosis or new diagnosis or relapse with the high disease burden. That's the number of cancer cells in the body. Most commonly, we give chemotherapy for the first maybe a month, two months, four months prior to transplant in an effort to decrease the number of cancer cells in the body. We try to get this as low as we can go, maybe even to undetectable and then would proceed with transplant. The transplant consists of high dose chemotherapy, which is given over one to six days, depending on the regimen.

(05:42): The patient’s stem cells are collected before transplant and reintroduced into the body after chemotherapy. The stem cells are collected before transplant. They're placed in a freezer so that they're not damaged by the chemotherapy. And then once the chemotherapy is out of the body, they're infused back into the blood. And fortunately, they're smart enough to know to go back to their bone marrow home. Within 14 days of the cell infusion, we do see counts recover to a safe level.

(06:09): Early recovery refers to the first 100 days when transplant toxicities and infection are treated. Transplant recovery can be divided into two phases, early and late. I think of the early as the first 100 days. This is when we're primarily trying to keep you safe and support you with any transplant toxicities. We support the blood counts with transfusions and growth factor. We put you on medicine to prevent infection and act quickly if you have a fever. We manage any GI upset. So, for example, nausea, vomiting, diarrhea, mouth sores are pretty common due to chemotherapy. We help make sure you're eating enough and drinking enough.

(06:50): Late recovery occurs after 100 days as physical recovery outside the hospital proceeds. And usually, once you get out of the hospital, the physical recovery begins. I consider late recovery days 100 and beyond. Here, we want to avoid infection. We'll talk a little bit more about that on a future slide. The physical recovery continues.

(07:13): Emotional recovery often doesn’t happen till after chemotherapy and transplant. Emotional recovery also continues. We do notice that people often have a lot of emotions after the treatment's over. We tend to get in fight or flight mode during chemotherapy and transplant to take care of what we need to do. And then once that's all over, we have more time to process all that we've been through and that can be surprising. Sometimes that that can be a more difficult period for some.

(07:40): Later recovery may be monitored an oncologist or BMT physician. We also focus on managing the late effects of transplant, which we'll move to in a little bit, and renewed focus on general health and age appropriate health guidelines.

(07:52): Post-transplant, the disease will be monitored by either your oncologist or the BMT physician. The frequency of assessment varies. It will often decrease over time if you continue to have a good response. It's usually done in a combination of labs, scans, physical exams, and potentially bone marrow biopsies depending on the disease treated.

(08:21): Patients are at risk of infection in the first year after transplant, with an increased risk of bacterial infection in the first 30 days. So, let's talk about late effects of transplant now, and we're specifically going to speak of them regarding physical health. Transplant patients are at increased risk of infection primarily in their first year of transplant. In the first 30 days, the biggest risk is bacterial infection. That is more likely to occur when the white counts are low. The bacteria that cause the infection are typically one from the body itself. We don't think about it, but we have a bacteria all over our skin, in our mouth, and in our GI tract. And those can sneak into the bloodstream occasionally. And without those white cells to fight, it can become an infection. Most important thing is to monitor closely and treat with IV antibiotics for fever.

(09:18): Viral infection risks continue through the first year of recovery. Risk of infection in the first year, then as primarily viral infection, the two things that we try to prevent are shingles or herpes zoster for those that have had chickenpox in the past or a recurrence of cold sores for people who have HSV herpes. We do this by putting you on acyclovir or valacyclovir, which is also called Valtrex, for a year as prevention.

(09:49): Even with a normal white blood cell count, the immune system will not yet be up to full strength. Respiratory viruses are the other main issue. These are things that you would acquire at home or in the community such as the common cold, flus, and then more recently, coronavirus or COVID-19. What we noticed in the first year is that, even though you have a normal white count, your immune system is not up to full strength again. So, if you were to get a common cold, you might experience symptoms longer and more severe, even occasionally leading to hospitalization.

(10:26): Prevention requires masking and avoiding public spaces and sick contacts. The prevention is masking, avoiding public spaces when you can, and avoiding sick contacts, I would say similar to the CDC guidelines when COVID 19 was at highest level in the United States. That's the same advice that we've been giving our post-transplant patients for years.

(10:50): Late bacterial infections are uncommon. If present, they may occur due to low immunoglobulins in the blood. That's a protein in the blood that fights infection. If there's concern of that, your doctor can check the levels and you may be eligible for monthly replacement. It's most common in people who've had treatment for B cell lymphomas prior to transplant.

(11:14): Guidelines for all recommended vaccines should be carefully followed. It's important to get your recommended vaccines post-transplant. We do recommend the COVID-19 series to be repeated post-transplant as early as three months. That's not just a booster, but repeating the entire series from the beginning. The flu vaccine, we recommend yearly starting three to six months post-transplant I think depending on the time of this season, that you're recovering. Childhood vaccination series is usually done through your transplant center. That's a combination of five vaccines requiring three doses of each. They can be given as early as 6 months and some wait to start until 12 months.

(12:02): Once that series is complete, it's recommended that you get an additional pneumonia shot called the Pneumovax six months after series completion. And then if you meet age requirements or other medical conditions, that would be recommended to be continued every five years for that population.

(12:26): Additional vaccinations may be recommended for certain age groups. So, a human papilloma virus, that's HPV, that's a newer vaccination that we use to prevent cervical cancer and head and neck cancer. This is only for age 26 and younger, and you would get three doses again, post-transplant. The meningococcal vaccine can be considered in college attendees ages of 18 through 23 or those with prior splenectomy.

(12:58): The shingles vaccination is available in the United States for ages 50 and older or younger who are immunocompromised. You can have two doses as early as 6 to 12 months post-transplant. If you get it early, that does not take away the recommendation for acyclovir or Valtrex for at least a year, but that can be added to the standard post-transplant vaccine series if you qualify.

(13:27): Live vaccines should not be administered for at least two years post-transplant. It's important to know that live vaccines should not be administered for at least two years after transplant or while on active chemotherapy. Examples, measles, mumps, and rubella, and varicella, or chicken pox are the two primary ones in the United States. There was a shingles vaccine that was live previously, but that has been taken off the market. So, I no longer caution about shingles vaccine eligibility, at least here in the United States.

(14:02): Lung toxicity can arise from both chemotherapy and radiation and may be treated with steroids. Now we're going to move on to organ toxicity beginning with the lung. Lung toxicity occurs during treatment or within the few months following. Risk factors include chemotherapy, such as bleomycin given to Hodgkins [patients] usually prior to transplant, brentuximab also Hodgkins [patients] prior to or after transplant, and carmustine BCNU, which is a drug used in the transplant chemotherapy regimen for many lymphomas, as well as any radiation near the lung field. The most common would be mediastinal. So, that's the middle of the chest. The lymph nodes that are there will often need some radiation. When you radiate, you do pass through other tissue to get there, and the lungs can be at risk. Fortunately, radiation is not that common anymore in our treatment paradigm.

 (15:08): So, the treatment for this would be to discontinue the causative agent. If one was still on it, seek a pulmonary evaluation. And sometimes we consider steroids if there's an inflammatory component. If the treatment's over with, there are still things you can do for your lung health, such as don't smoke, and wear a mask when you're around certain chemicals or inhalant exposure risks.

(15:36): Radiation also raises the risk of heart problems although better radiation techniques are now used. Similar to the lung, mediastinal radiation also increases a risk to the heart specifically of coronary artery disease or heart failure. There was an old study of patients who received mediastinal radiation for Hodgkins, but these were all treated prior to 1995. So, this was a long time ago. They were followed for many years and they determined that the risk for cardiac health, such as heart attacks or coronary artery disease, was three to five times greater than that of the general population. I can't speak to the risk today, but we do know that it's significantly lower. We have better radiation techniques that now map the radiation to be more intense at the areas that we're trying to target with less radiation to the off-target sites.

(16:35): Anthracycline chemotherapy can also elevate heart risks. The other risk to the heart would be primarily used prior to transplant chemotherapy called anthracycline. Some of you might know it as the red devil. At certain amounts, it can increase the risk of heart failure dramatically. At moderate amounts, the risk is fairly small. So, we make sure that you don't get more than a certain dose in a lifetime, but to often make you aware of the risk when receiving this. There's no specific screening for heart post-transplant or post-chemotherapy in adults, but certainly seeking medical attention for chest pain, shortness of breath, things like that would be indicated if needed.

(17:26): Maintaining overall heart health can mitigate these risks. So, what else can you do for your heart? Well, you may have had an exposure risk before, but there's still some other risk factors you can modify to make sure you have the best heart health [so] that you can live healthy. Get screened for other medical conditions and treated. Risk factors for heart disease include high blood pressure, high cholesterol, and diabetes. If diagnosed but treated appropriately, this risk can be minimized or prevented.

(18:06): Neurologic toxicities may also arise. All right. There are two neurologic toxicities that I'm going to talk about, the more commonly observed post-transplant. The first is peripheral neuropathy. So, that's damage to the small nerves in your hands and feet caused by certain types of chemotherapy. The treatment, of course, would be to stop the chemotherapy if you were still on it. But if that's in the past, the primary treatment [is] supportive care., There are some medicines that can help prevent the pain, help with the pain. And then similarly, there are some other conditions in life that can cause neuropathy or therefore cause worsening of neuropathy.

(18:46): So, it would be important to focus on prevention as well. Diabetes is probably the most common cause of peripheral neuropathy, specifically uncontrolled diabetes with high sugars for a long time. And so, being screened for that and making sure you're on appropriate treatment is important to prevent worsening.

(19:11): Chemo brain can affect higher level functioning but usually improves with time. And then there's chemo brain. I think most of us have heard of that. It's during or after chemotherapy treatment where it primarily impacts your higher level function, your ability to remember things, attention. Most people can't tell that you have chemo brain. You notice because you don't think your thinking is quite normal. Maybe you go back to work and you don't feel as sharp as you were before. Fortunately, that gets better over time for the majority of people.

(19:56): There are some treatments, if it lingers, like a neurocognitive rehabilitation, which is like exercise for the brain and then also some stimulant medication. I want to caution you, too, that depression and anxiety can also cause mental fog and can be a great mimicker of chemo brain. So, if this is ongoing and there may be a component of depression and anxiety, that treatment alone might help lift a lot of that fog.

(20:36): Long term effects for the eyes and mouth may occur but are not common. All right. Long term effects for the eyes and mouth are uncommon. We sometimes see some cataracts or earlier cataracts in those exposed to total body radiation or high dose steroids. Those can be fairly easily removed by a physician focused on the eyes.

(20:56): Mouth, not many long term risks, except for those that receive high dose radiation to the head and neck at some point in their treatment that can impair the salivary glands, and you don't make enough saliva, and that can lead to increased risk of cavities and tooth decay. So, for those people and really for all of us, the best thing to do would be to go get routine screenings and care with your dentist.

(21:29): Thyroid complications can arise but can usually be treated with medication. All right. Thyroid conditions are common condition in the general population and can affect some post-transplant as well. The primary risk of this would be radiation to the head and neck, but again, any of us could potentially have this despite the treatment. The thyroid gland controls your metabolism and tells your body how to use its energy.

(21:54): Hypothyroidism is low thyroid function. The risk is radiation to the neck, like I said, and the symptoms are fatigue, weight gain, constipation. So, the treatment's fairly easy. You screen and check thyroid levels and you're put on a pill that replaces your thyroid hormone. This can be done, and is done routinely, by your primary care physician if you have these specific complaints.

(22:23): Bone thinning is not common but weight bearing exercise or certain medications to strengthen bones can be helpful. All right. Bone thinning is fairly uncommon after autologous transplant, specifically. The most common risk of bone thinning, that's osteopenia or osteoporosis, are frequent steroid use. So, high dose steroids that might be in some of your regimens that go over a long time. Or maybe you have another condition which requires chronic low dose of steroids.

(22:50): Low testicular ovarian function, such as low testosterone, can increase the risk of bone thinning. And then of course, as we all age, our risk of bone thinning is increased. Women tend to be more susceptible than male because testosterone is protective for bone health for men.

(23:13): To prevent, we recommend weightbearing exercise. So, that's things like walking or lifting lightweights. Hormone replacement, of course, if you're deficient. The way to screen for this is called a DEXA scan. So, that's maybe every two years, a bone density scan. I don't do this for all of my auto transplant patients, but I do recommend it for those that are in the higher risk category that I mentioned previously.

(23:46): There is treatment for bone thinning with a bone strengthening medication called bisphosphonate or Zometa. For those of you that have undergone treatment for myeloma, this is actually often part of the regimen and so you may have already received this medication.

(24:05): Hormone deficiencies can impair fertility or sexual function. Both men and women can have other hormone deficiencies after transplants that impair fertility or sexual function. For men, low testosterone can be due to chemo or radiation and the risk is also increased with increasing age. Symptoms include fatigue, difficulty getting an erection. And the treatment is to replace with all the testosterone hormone is indicated by checking testosterone levels.

(24:38): Now, low testosterone is not the only cause of sexual dysfunction. So, if that's ongoing, it's important to seek help from an expert. Either your primary care physician or a urologist would be the ones who most commonly treat that.

(24:54): There is a risk of infertility with transplant, with any chemo or radiation. It's hard to estimate the risk because it varies by regimen. But if you're of childbearing age and curious, you can have a specialist evaluate you. I generally recommend waiting 6 or probably 12 months post-transplant.

(25:20): Also, a reminder that transplant is not a form of contraception. We do tell you there's a risk of infertility, but this is not a guarantee. So, make sure you're taking appropriate precautions if indicated.

(25:36): Women may experience hormone imbalances that mimic menopause but can be treated with topical or oral hormones. Women similarly can have low estrogen or other hormone imbalances. Menstrual cycles often stop during chemo and transplant and depending on age may or may not return. The risk factors, of course, again are chemo radiation, and the hormone imbalance could be temporary or permanent depending on the age and likely the regimen that you received. Symptoms of hormone imbalance are similar to what we think of menopausal symptoms, hot flashes, vaginal dryness, pain with intercourse. The treatment would be topical or oral hormones if indicated. And there's also some

(26:24): The presence or absence of a menstrual cycle doesn’t indicate or preclude fertility. Similar to men, we can't quantify the exact risk of infertility. It does vary by treatment and regimen. We want to remind you that lack of a menstrual cycle doesn't mean infertility, but also resumption of a menstrual cycle after treatment also doesn't guarantee return of fertility. So, a specialist can evaluate you. We recommend waiting at least 12 months post-transplant for this. And for those that are able to get pregnant, fortunately, there does not appear to be an increased risk to the health or of the mother or the baby after transplant.

(27:06): There’s minimal risk to breast health unless there was high dose radiation to the chest. There's minimal impact to breast health with transplant. The primary group who would be at risk would be those that receive high dose radiation directed toward again, the middle of the chest, the mediastinum that goes through breast tissue. For this group, it's recommended to begin screening mammograms eight years post-radiation. If you get radiation while you're young, no earlier than [age] 25 and no later than [age] 40. So, everyone should start routine mammograms at 40. Breast cancer is common in the general population and fairly easy to treat and cure if you catch it early. So, screening mammograms remain important after transplant.

(27:53): Secondary cancers due to chemo and radiation are a small risk for most patients. Unfortunately, there is a small risk of getting another type of cancer, once you've had treatment for different cancer and that's due to effects of chemo and radiation as we talked about in the last slide. Smoking, of course, contributes a significant amount. There is some association with younger age at the time of treatment, but I think this probably represents a population that maybe lives for 30 to 50 more years and has a chance to develop more second cancers. Whereas if you're treated, when you're older, you may not live long enough to develop a second cancer.

(28:35): Bone marrow disorders are rare but can develop into secondary cancers. Bone marrow disorders can occur in a small subset of patients after transplant. A primary cause is radiation or certain chemotherapies, like alkylating agents, and even a small association with Revlimid, which is used for myeloma. The bone marrow disorders are called myelodysplastic syndrome, or MDS, which is a bone marrow that functions poorly and doesn't make the proper amount of blood cells that you need and can also turn into, or become, initially, an acute myeloid leukemia, which requires urgent treatment.

(29:17): Having a complete blood count at least once a year is recommended. There's no specific screening recommended if you've had exposure to these prior, but I would say that you should be getting routine labs with at least your primary care physician, a complete blood count once a year, or if you're falling closely with your oncologist or bone marrow doctor, you may be getting that more frequently with your routine labs. If your blood counts were to be abnormal and we couldn't understand why, we would go then investigate with bone marrow biopsy.

(29:53): Solid tumor risks are unlikely to arise. The risk of solid tumors after auto transplant, I would say, is pretty minimal. These are things like skin cancer, head and neck cancer. The primary risk is radiation. Those that have had radiation. And then we do see this more commonly in our donor populations, our allogeneic transplant who've had donor cells, due to immunosuppression that's required after transplant. I think for auto transplant group, lifestyle probably matters more than history. That's sun safety, smoking, and things like that. Keep maintaining a good weight, that can prevent second cancers in the future.

(30:42): Fatigue is common for transplant recipients, but prolonged fatigue should be examined for other causes. So, fatigue is something that everyone who's been through this has had at one time or another. It's extremely normal after transplants. It does improve over time. And so, I try to encourage my patients not to get discouraged, because sometimes it does feel like it takes longer than you would like. We recommend that you're active when you can. We can't get stronger unless we move our bodies. But also, be really attentive to your body and rest when it tells you to rest. Be aware, though, of other treatable causes of fatigue, especially when the fatigue is prolonged.

Dr. Jana Reynolds (31:23):

So, just like chemo brain, depression, anxiety, stress can be great mimickers of chemo fatigue and so make sure we're addressing those if they're ongoing as well. Hormone changes, low testosterone, low thyroid may be contributing. And then if it's prolonged, we always have to think, too, of exacerbation of other medical problems. Do you have undiagnosed sleep apnea? Is there maybe something new going on with your heart? We want to be careful not to blame the chemotherapy, the transplant, too long and not look into other causes if it's ongoing.

(32:04): Mental health challenges can also arise. So, we can't talk about physical health without mental health because I don't think you can have one without the other. So, the next few slides, we'll focus on the mental health component and late effects. After transplant, many find that reintegrating into life can be challenging, reintegrating with your family, significant other, children, parents. Sometimes this treatment strengthens relationships. Sometimes it causes some difficulty, and those relationships need to be attended to. These people are often your caregivers and need to be prioritized again to making sure they're taking care of their own health.

(32:54): It can take time and patience to reintegrate into family and work relationships. We have to reintegrate with our friends, our friend networks, and maybe you feel a little bit different than when you started and maybe you have to figure out what's right for you. Work and home responsibilities come back. Unfortunately, most people have to take a lot of time out from life to do transplant, which can be a financial strain, a job strain. And getting back to those can be difficult, especially if you're having some prolonged effects like pain or fatigue [that] can make it especially difficult.

(33:27): And then facing the unknown is always hard. I think wondering if this cancer might come back, if you're going to have to deal with this again, I think that does get better over time.

(33:42): Scanxiety and fears about cancer returning can pose mental health challenges. One term that I really like and I don't know who thought of it first, but is scanxiety, scan anxiety. It's that feeling you might get when a year or two years after transplant and you're going in for your scan just to make sure everything's fine. Or you're going in for your labs, or whatever you may be doing, and you just feel really horribly anxious and nervous until you get the results. And then maybe relieved because the results were good but wonder why that was so hard to go through. I think there's a little bit of post-traumatic stress or PTSD component sometimes about going through these screenings.

(34:22): Once your cancer is in remission, that brings back that initial feeling of you were fine one day, and then the next day, someone told you had cancer. And I think it brings those memories back. Just know that that is fairly normal. We do hear that from a lot of our patients. And then there's the finding the new normal. Maybe things have changed in your life. Maybe they're not going to change back. Maybe change for better or sometimes change for worse but figuring out what that life is and how it looks moving forward is what we refer to as figuring out that new normal acceptance that maybe some things have changed is helpful for your ability to move on.

(35:10): Depression and anxiety are also more common in cancer survivors but can be treated with counseling and medication. So, briefly, depression and anxiety, this is more common in people who've been diagnosed with cancer. The risk factor for this, there's a couple of them. For those that have been treated for an episode of depression or anxiety at some time in their life before, they're going to be more susceptible to a recurrence of this during or after transplant. That would mean, maybe, restarting medications or a dose increase in medications. From our studies, younger patients, male and lower income, have a more of a tendency to depression. The risk over time specifically related to the cancer event can decrease if you continue to do well. The best treatment is usually a combination of counseling and medication. So, it's important to ask for help if you're struggling.

(36:07): Most effects of transplant are transient and not permanent and taking an active role in post-transplant care is important. All right, the good news. You're not alone. There are a lot of friends, families, doctors, nurses, all out there rooting for you if you're someone who's gone through an auto transplant, and there's a lot of people attending this conference today with the same curiosity of what to do and how to move on with life. I'm glad to be part of it. Most autologous transplant patients can return to a similar level of functions then go back to work and activity. That's the good news about auto transplant. Usually, the effects are transient and not permanent. Again, acceptance of any changes though in your path can help you move forward and you can improve your health by taking an active role in your post-transplant care and routine health maintenance.

(36:56): Maintaining overall good health with appropriate screenings and preventive measures can maximize quality of life. So, I might bring up my last slide, which is a reminder to don't miss the forest for the trees, the trees with the cancer, which get quite a bit of focus during initial diagnosis and treatment. And then once we're through that, we need to remember to look around at the forest, which is our overall physical and mental health and make sure we're giving that equal opportunity for health and improvement. Remember to prioritize your general health in addition to your cancer follow-ups. Ask, "What can I do for my health?"

(37:31): Continue your age appropriate health screenings, for example, blood pressure, diabetes, cholesterol, colonoscopies, mammograms, pap smears, all those things. If you're not sure if you're due, you should ask your primary physician what you need.

(37:43): Get routine dental exams, don't smoke, exercise, wear protective clothing in the sun, eat healthy, and try to maintain a healthy weight. So, I will stop here. Thank you for your attention today, and I'll do my best to answer some of your questions.

(38:02): [Michala O'Brien]    Q & A.  Thank you, Dr. Reynolds, for this excellent presentation. We will now begin to take questions. Dr. Reynolds, someone asked, "My husband is due for a stem cell transplant in July. How safe is this procedure during COVID and how can we best prepare him for this procedure?"

(38:34): [Dr. Jana Reynolds]  Oh, that's a great question. We did have a lot of concern early in COVID about how that would impact transplant and transplant risk. I will say, this summer is different than two summers ago because we know better how to prevent it and we have some medications to treat it. The vaccinations are important to get prior to transplant. Sometimes people do hold some immunity from those. There's now a new antibody approved that can be injected. It's a COVID prevention antibody that we are giving to our patients that are undergoing transplant. It's called Evusheld to protect them for the three months or so before they can get their vaccines again.

(39:27): Once vaccinated, we still recommend our patients to be cautious throughout that first year of transplant, just continuing to be smart. Different also than COVID before is we do have some antibody treatments and some oral medications for treatment. So, I think we're in a much safer place now to address for transplant during COVID, but still important, the primary prevention is wearing masks in public and just avoiding unnecessary contacts if you can.

(40:10): [Michala O'Brien]    Okay, great. Next question. Is there a reason that you would not recommend rituximab after a BMT for mantle cell lymphoma, why you would not recommend it?

(40:26): [Dr. Jana Reynolds]    Well, that's a newer indication. So, that was not something that we used to do. Some might be put on a different drug. The standard is rituximab, but there's some other drugs, specifically BTK inhibitors like Ibrutinib or acalabrutinib, that one may be put on. And then of course in the era [of COVID], rituximab does make you a little more susceptible or it decreases your immunity for longer. So, in the era of COVID, there also could be a consideration of safety. But again, you just have to continue to be cautious as long as you can. I hope that answers the question.

(41:14): [Michala O'Brien]    The next patient wants to know if you still have neuropathy - their toes are still numb - do you recommend going to a neuropathy clinic for treatment or any other suggestions?

(41:27): [Dr. Jana Reynolds]    Well, good question. When the toes are numb, it sounds like when you walk, you don't feel them as well and that might be frustrating. I'm not hearing that they're painful, which is what clinics primarily treat is the pain associated with it. They are reasonable if you're having pain to get on medication. Sometimes they do some nerve stimulation and things like that. I'm not sure of the true efficacy of that.

(42:02): Unfortunately, most of the damage is already done, but I think if you're really uncomfortable, it's important to keep seeking out help for your neuropathy and a clinic would definitely be reasonable to try. We treat neuropathy a lot in our clinic because we see it. So, sometimes your primary care doctor or your oncologist can try to help treat it. But again, we can't do much about the numbness. For those that have the pain component of the neuropathy, we can help try to reduce that pain.

(42:40): [Michala O'Brien]    All right, somebody from Florida is asking they're years post-op for non-Hodgkin lymphoma and their energy level is still not there. Is this normal?

 (42:54): [Dr. Jana Reynolds]  No, it's not normal, I would say. There's a couple things here that come to mind. I wonder if there's something else going on as well, right? As I said, in my slide, any other medical conditions that might be contributing, any lifestyle things that might be contributing, and those would probably be the primary focus. We typically don't see fatigue that far out.

(43:27): Now, there's also four years later, you're also five years older than before you started transplant. You've been through a lot. So, there's also you having to reset expectations a little bit of maybe you are not as fit as you were, because you're five years older or not as energetic maybe. Maybe you do need more naps. But I would say I would strongly recommend looking at things like anxiety, depression, sleep apnea, some things like that to see if to see if there's something else modifiable about that.

(44:04): [Michala O'Brien]     Great, thank you. The next question, someone's asking, how do you reintegrate into life post-transplant with COVID? We're already masking and holing up in our home. What are some suggestions?

(44:21): [Dr. Jana Reynolds]    Oh, this has been so hard. When COVID first started, there were some of my patients that were just about to get out of that window of needing to be extra cautious and then they had to stay in, and that feels like it's never changed. I think it's been challenge for everybody. And I know with being at more risk after transplant, it's especially difficult. I sometimes think of the way I would just think of how we would do it as a general population during COVID, for anyone who was higher risk or anyone who didn't want to get it or spread it, was to get all the vaccinations or protective immunity that you can get that's available. Masks are really effective.

(45:27): And so, when you're doing something, I know the mask requirement has dropped in many places, but you can still put it on. I recommend some medical mask over just a cloth mask. If you are going to reintegrate, wearing a mask to go do things. And then eating outside, visiting people outside, some lifestyle modifications where you might be able to ebb into having a little more of a life, but still keeping yourself safe. And ultimately, it's a personal risk for everyone.

(46:07): We can recommend you stay home all day long and it's up to you to decide what you are willing to try or not. But I would say masking, being vaccinated, and thinking smartly about the spaces you share. If you do those things, you may be able to get a little more into life, now that we know those things are pretty effective.

(46:31): [Michala O'Brien]      Great. Somebody else is asking, "I'm 71 and I'm lactose intolerant. How can I tell if I'm getting the right amount of calcium intake in my diet?"

(46:43): [Dr. Jana Reynolds]   That's a great question. In the American diet, many of our foods are fortified and you don't necessarily just have to drink milk to get calcium. I would say, though, being at the age of 71, I think the most important thing would be a bone density scan if you haven't had one, a DEXA scan. And if there's any sign of thinning, despite what your calcium level is, getting on recommended daily, calcium. Usually, it's combined with a daily vitamin D pill. So, I think that there's a high risk of osteopenia, osteoporosis for age 71, especially a woman. I think you said, or maybe you didn't, but I think we may be looking into needing to be on some supplementation anyways if we're starting to have some bone thinning.

(47:48): [Michala O'Brien]    Okay. Thank you. When do you think a patient needs to talk to professional when you start to feel the scanxiety that you mentioned?

(48:01): [Dr. Jana Reynolds]    I think that if it exists a few days around your scan, that's just normal. I think that if it goes on and I think that in between scans, if you have fleeting thoughts of, "Oh, I hope this doesn't come back," that's okay. But I think when you become overwhelmed by the anxiety, probably the scanxiety, right, is not the fear of the cancer coming back. If you're more days than a not, you're not okay, I think that's the clinical depression or anxiety that definitely needs some treatment.

(48:47): I think if it's fleeting and associated with your horrible, terrible, every three or six months scans, then that's normal and you may want to share with your family or friends how it makes you feel. I think that everyone gets real excited for you to go get tested, because they think you're going to be great, but you don't always feel that way. And so, maybe minimizing the language or helping them understand how they make you feel might-

(49:15): [Michala O'Brien]   Is the purpose of continued acyclovir to prevent shingles?

(49:21): [Dr. Jana Reynolds]     Yes, for the majority of people. Now, if you have oral herpes, where you get cold sore breakouts, or genital herpes, where you get breakouts, sometimes that would be [inaudible], which is the other reason for it as prevention.

(49:38): [Michala O'Brien]   Okay. We're going to take a couple more questions because we are running at a time. How likely is it to get a lung infection after a BMT by working in the yard, being outside with grass, dirt, et cetera.

(49:56): [Dr. Jana Reynolds]    The biggest risk is for those that have had a donor transplant that are on immune expression, on high dose steroids. So, I would say after an auto, the risk is fairly low, but we really caution people to be careful. If we think about wet dirt or grass or hay, there are fungus and opportunistic infections, we call them, that can live in there where the normal person, if inhaled, the immune system would knock them come out. But your immune system, again, is not fully functional for up to a year post-transplant. [It gets] better every month. But we do caution people from initially digging in dirt and baling hay. And over time, that risk goes down. If you start doing that, one of the things that could be helpful is wearing a mask and gloves. But I would say that risk is probably primarily in the first six months.

(51:09): [Michala O'Brien]     Great. What treatment would you recommend for myelodysplasia following CAR T immunotherapy?

(51:20): [Dr. Jana Reynolds]     It depends. There is a big spectrum of myelodysplasia. I suspect that may have come from a long history of chemotherapy followed by CAR T, [that] is usually the reason. It can vary between just watching it if it's just low dysfunctional counts without other high risk factors versus the curative treatment, before it would be an allogeneic, so a donor cell transplant, but we do not transplant everyone with myelodysplasia. That's just for certain people. So, it can vary based on how much the myelodysplasia impacts you. If it's just mildly low and you don't need transfusions and the marrow looks stable, you can monitor, versus if someone thinks it's higher risk, you can treat with some supportive chemotherapy or move on to transplant.

(52:23): [Michala O'Brien]    All right. Is 78 too old for an autologous transplant?

(52:29): [Dr. Jana Reynolds]   For 99.9% of people, but I've met a few 78-year-olds that are fitter than some of my 58-year-olds. So, we typically think 75 should be the upper limits, but I guess if someone... There's a physiologic age. And a biologic age is not actually your physiologic age. So, we will take that into account, sometimes, in seeing if you're over the age limit that we normally think of for transplant.

(53:08): [Michala O'Brien]   Okay. There's another acyclovir question. If you take acyclovir, do you need a shingle shot?

(53:15): [Dr. Jana Reynolds]     As far as acyclovir goes and the timing of the shingles vaccine, our recommendations for acyclovir are going to be there with or without the shingles vaccine. So, it's not necessarily beneficial to get the shingles vaccine while you have to be on acyclovir. So, once you're done with it or approaching and being done with acyclovir, it might be worth getting the vaccination. Now, that's when you approach same risk of general population of shingles.

(53:54): So, the real role of the vaccination is for the general population, who as we age or immunocompromised, have a higher risk. And so, once you get out of the acyclovir window, if you're in that population, it would be recommended, but I don't think it's necessary to do both, except that it does take two vaccines a little separate. So, if you overlap that with acyclovir, then you could potentially come out with more immunity once you stop the acyclovir.

(54:23): [Michala O'Brien]    Okay. This will have to be our last question for the day. We're running out of time. The question is, after more than a year of transplant, is a patient's immune system still immunocompromised, or does that depend on their blood counts?

(54:42): [Dr. Jana Reynolds]    So, it generally doesn't depend on blood counts, because the majority are the counts are going to be normal. The immune system is greater than just the blood count though. Without counts, you don't have an immune system either. I think it's really hard to estimate. I think that it depends on whether you're on any form of maintenance chemotherapy. And so, I'm sorry. I think I skipped my slide earlier, but there's a few diagnoses where maintenance chemotherapy is recommended. Other people are just watch or surveillance after transplant, depending on the disease and the studies behind it. If you're on an ongoing chemotherapy, that is going to prolong your

(55:31): Do we think you're completely normal at one year? I'd say, you're very close to it, but slightly maybe you're 95%, 90%. So, we don't really know how to quantify the risk except it goes down over time. I would say if you're not on immunosuppression, which most of our auto transplants are, you are not on chemotherapy and you've recovered nicely from transplant, at a year or at least by two years, it should be pretty much fairly normal.

(56:09): Now, you are at risk -you may not have carried forward immunity from some of the viruses that you saw in the past. So, for example, if you have a certain strain of a cold, you don't get that cold again because you have immunity to it. You may have lost some of your immunity. So, you may notice that you're the one picking up all the respiratory viruses, because you don't have that protective immunity that you had gathered in life. So, I think it depends on a variety of things.

(56:38): And then I think with regard to COVID, I also remind everyone that there's separate recommendations outside of transplant. Okay, we think your immune system's better. How old are you? Are you at the increased risk or do you have other comorbidities? So, we have to think about, at least in COVID times, the whole picture and make our best judgements from there.

(57:07): [Michala O'Brien]   Closing. Great. On behalf of BMT InfoNet and our partners, I'd like to thank you, Dr. Reynolds, for your very helpful remarks and thank you, the audience, for your excellent questions. Please feel free to contact BMT InfoNet if we can help you in any way. Enjoy the rest of the symposium. Thank you.

(57:28): [Dr. Jana Reynolds] Thank you.