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

Transcript of Presentation.

(00:00): [Thom Stewart]: Hello, everyone. Welcome to the workshop Strive to Thrive! Understanding your Health After a Transplant Using Your Own Cells. My name is Thom Stewart and I will be your moderator for this workshop.

(00:14): Before we begin, I'd like to thank Sanofi whose support helped make this workshop possible.

(00:21): Speaker Introduction. It's my pleasure to introduce today's speaker, Dr. Jonathan Lambird. Dr. Lambird is an Assistant Professor of Hematology and Oncology at Wake Forest University School of Medicine in North Carolina. He has a special interest in blood and marrow transplantation, chemotherapy, and cellular therapies for patients with multiple myeloma and other blood cancers -- such as acute leukemias and myelodysplastic syndrome. Please join me in welcoming Dr. Lambird.

(01:00): [Dr. Johnathan Lambird]: Thank you for that kind introduction, and I'm looking forward to talking to you about thriving after the completion of your autologous stem cell transplant -- or transplant using your own stem cells.

(01:13): Overview of Talk. Today's learning objectives are to review the late and long-term complications that may develop after an autologous stem cell transplant. We'll discuss the risk factors for developing each complication and outline strategies to identify and address symptoms that may be encountered after an autologous stem cell transplant (auto-transplant). My goal for this talk is to help individuals who have had an auto-transplant and their loved ones to know what to expect after completing this intensive form of treatment.

(01:43): I wanted to start by talking through some steps I assume have already occurred with many of you. Most patients who go through an auto-transplant have a form of cancer, most often a blood cancer like lymphoma or multiple myeloma. Sometimes patients with germ cell tumors -- also referred to as testicular cancers – undergo this procedure as well.

(02:10): The procedure includes collecting stem cells from the person who will receive the chemotherapy, followed by administering very high dose chemotherapy to kill the cancer. Unfortunately, the chemotherapy is also toxic to the bone marrow and blood-forming cells. Therefore, after chemotherapy has been administered, those stem cells that were taken out prior to treatment are reinfused as a form of rescue. This allows the blood-forming cells to regrow after the chemotherapy cancer treatment.

(02:42): As I looked through the topics that will be discussed during this conference, I realized there used to just be two forms of stem cell transplants that we would talk about, and now there's a third – CAR T-cell therapy. Because this is an early talk in this conference, I wanted to provide an overview so that you had an idea of each specific form of transplant.

(03:05): I've got three columns here labeled ‘HSCT,’ ‘ASCT,’ and ‘CAR-T’. A hematopoietic stem cell transplant (HSCT) is when someone gets a stem cell transplant from a donor, a relative, or somebody they probably have never met. An autologous stem cell transplant (ASCT), is the transplantation of stem cells collected from the self – that will be our focus today. CAR-T cell therapy (CAR-T) is a relatively new form of therapy that involves giving mature, engineered, immune cells (T-cells) from the individual back to themselves after a treatment course of chemotherapy.

(03:43): The chemotherapy doses used for autologous (ASCT) and allogeneic (HSCT) stem cell transplants are very intensive. Chemotherapy given prior to CAR-T tends to be less intensive.  

(03:56): The part of the treatment that is providing the most benefit in actually killing and destroying the cancer varies with each form of transplant. The source of benefit with an allogeneic transplant (allo-transplant) is the infused cells from the transplant. The process of replacing the patient’s stem cells with donor stem cells is the action that helps treat the cancer, as the goal is for the donor cells to initiate an immune response to the cancer.  

(04:05): With an autologous transplant (auto-transplant) – our primary focus for today – the chemotherapy is the primary treatment in destroying the cancer, not the cells infused during the transplant.  

(04:14): In CAR-T, the infused T-cells do the heavy lifting to treat the cancer.

(04:19): Late effects for these treatments can be quite variable as well. In allo-transplants, many side effects can be due to the intensive chemotherapy administered prior, as well as from the immune effects from the transplant itself. In auto-transplants, the side effects mainly stem from the chemotherapy treatment. In CAR T-cell therapy, there are fewer chemotherapy-related side effects, but there can be some very unique long-term side effects. This will be a topic for discussion later in this conference.

(04:54): This is a graph comparing patients with multiple myeloma’s reported quality of life in those who had an auto-transplant and those who did not. Both lines follow similar patterns during treatment, but in the patients who had an auto-transplant, there’s a decline in their reported quality of life -- meaning things like energy and activity. With time, it recovers, and the quality-of-life reports return to its baseline value or maybe even a little bit better than those without transplant. That's the key takeaway here; you might go through a difficult period of time during your transplant treatment, but we are going to support you through that journey to provide you with an improved quality of life after you’ve completed the transplant.

(05:48): In the first six months, there are early side effects that can be expected. This can include low blood counts, increased risk for infections, fatigue, and weakness. You may require blood transfusions, and your doctor may have you on a couple different medications to prevent certain infections. You may also notice you have altered taste sensations and decreased appetite.

(06:35): There are a few things we do to continue monitoring and treating you after your auto-transplant. For multiple myeloma, patients routinely go back on what we call ‘maintenance chemotherapy’. That's typically drugs like lenalidomide (Revlimid) or daratumumab (Darzalex). Treatment is tailored specifically to your case, so it's a good thing to make sure you discuss with your transplant doctor.

(07:05): Patients with lymphoma may or may not have maintenance chemotherapy after transplantation. When maintenance is used, it's usually drugs like Rituximab or brentuximab. However, it's less common for maintenance chemo to be utilized.

(07:23): Your doctors are going to want to monitor your lab work, potentially order some specialized scans, and occasionally perform a bone marrow biopsy to monitor for possible disease recurrence after transplantation. The specific tests that you receive will be individualized to your specific case.

(08:02): There are things that you should expect, and things that you can do, to overcome the possible long-term consequences of stem cell transplant. I think of this in terms of physical recovery, mental recovery, and social recovery. Usually this starts around the six-month mark after transplantation.

(08:27): In terms of physical recovery, many of my patients will return to their previous levels of activities -- including returning to work -- at about six months. We encourage people to re-engage in physical activity as well, as this will help their physical strength and stamina come back faster.

(08:51): There's also a mental component that comes with recovering after stem cell transplantation. Engaging in things like support groups may be very beneficial to give you tools and resources if you are experiencing some lingering effects of brain fog.

(09:06): There's a social recovery as well. During treatment, our center recommends that patients reduce the number of social interactions they have to reduce the opportunities for infections and exposure to germs. For most patients, their white blood cell count goes to zero and they need intensive antibiotic therapy just to prevent normal infections that a healthy immune system would otherwise be able to fight. After the six-month mark -- and for some time after -- we recommend a stage re-engaging in social activities. It can be beneficial to see family members, extended family, and friends that you haven't seen in a while, but getting back into the swing of things after being out of it for so many months can sometimes be bittersweet. We recognize this, and try to provide support and guidance during that process.

(10:15): It's important to realize that the different components of the immune system recover at different rates. At our center, we typically keep people in -- or nearby -- the hospital until their neutrophil counts (a type of white blood cell) have recovered. However, there are other forms of white blood cells, and other components of the immune system, that may take six months to a year to recover.

(10:41): We usually recommend starting the re-vaccination process around six months. There are certain shots -- specifically COVID and flu -- that data supports administering as early as three months after stem cell transplant. However, each transplant center has their own re-vaccination schedule.

(11:09): This is a list of the vaccines that we recommend. While each of these shots may only appear once on the list, it may be a vaccine -- like pneumococcus and Hepatitis B – that requires a series.

(11:29):  The measles, mumps, rubella (MMR) vaccine is a live vaccine. At our center, we previously had recommended waiting two years after an auto-transplant until administration of the MMR. Because there have been some outbreaks in the community recently, we're now recommending our patients receive it at the one-year mark instead. There are also discussions around administering the MMR in patients receiving maintenance chemotherapy – such as lenalidomide (Revlimid), daratumumab, or even rituximab and brentuximab. I recommend speaking about this with your transplant doctors for their specific recommendations.

(12:18): Certain vaccines that are specific to travel may be beneficial as well. I had a patient who wanted to visit family in Africa after her transplant. By that point, she was pretty far out from her transplant, but I was still a bit worried about her immune system. She was still on medication that reduced her immune system, so I sent her to an infectious disease specialist. They recommended a Hepatitis A vaccine and giving her intravenous immunoglobulin (IVIG) to boost her immune system. While that's not routine for domestic travel, that may be beneficial for international travel. At the end of the day, the best thing is discussing your plans with your doctor and potentially involving a specialist.

(13:06): Another potential risk of auto-transplants are secondary cancers. The risk of secondary cancers is somewhat difficult to pinpoint because patients who have auto-transplants are treated for different types of cancer, and receive different types of therapy.

(13:38): One long-term follow-up study (referenced at the end of this presentation) found that 6.7% of patients who had an auto-transplant developed a new cancer within 15 years of their treatment. Now, that’s still 93% of patients who didn’t, but 6.7% is still a higher percentage than the general population.  

(14:07): Secondary cancers that we most commonly see after auto-transplants are blood or bone marrow cancers – such as acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and myelodysplastic syndrome (MDS). Additionally, we see solid tumors like lung cancer, oral cavity cancer, certain types of brain, thyroid, breast, and even skin cancers like melanoma or non-melanoma.

(14:36): There are some factors that may put someone at higher risk for developing a secondary cancer. Getting an auto-transplant at a younger age, having radiation treatment, and the amount of chemotherapy received during treatment can predispose someone to developing a secondary cancer. Smoking is certainly a risk factor as well.  

(15:13): Because of this increased risk in developing secondary cancers, it's very important to keep up with routine cancer screenings, like prostate cancer screening, mammograms, pap smears, and colonoscopies. Seeing a dermatologist for a high-quality skin exam is important. For smokers or former smokers, lung cancer screening with chest CTs are important. Other focused tests may be indicated due to any personal or family history of cancers.

(15:50): The recommended frequency of these tests is usually similar to the general population, but we really encourage patients to be vigilant and not delay their appointments. We certainly don't want to miss the opportunity to identify and engage early with issues that, if left untreated, could be a real problem.

(16:13): In terms of screening for blood cancers, routine annual blood work -- like a complete blood count (CBC) -- should be done to identify abnormalities that could predispose to those types of cancers if they arise.

(16:32): There are things you can do to help reduce your risk of secondary cancers. Maintaining a healthy diet and regular activity is very helpful. We also recommend using sunscreen. These little things can be really helpful, especially for patients who are predisposed to developing skin cancers. And, as previously mentioned, being vigilant in having routine health exams and screenings.

(16:52): Smoking cessation can make a huge impact in reducing your risk of cancer. Any of your doctors would be happy to discuss adjunctive therapies to help you quit smoking, or you can make use of supportive interventions like the 1-800-QUIT-NOW.

(17:40): Long-term cardiac issues can also occur after an autologous stem cell transplant, and there are a variety of issues that may arise. They could be as common as things like high blood pressure or it could be severe things like heart failure, cardiovascular disease or arrhythmias. The risk for having heart problems increases two to three times after an autologous stem cell transplant.

(18:05): Factors that increase your risk for heart problems include having certain types of radiation to the chest, and being treated with certain types of chemotherapies -- such as anthracyclines – which typically is a red chemotherapy sometimes referred to as ‘the red devil’. Smoking can predispose patients to heart problems post auto-transplant as well.

(18:31): Things you can do to help decrease this risk include engaging in regular exercise, and eating a healthy diet rich in whole grains. Smoking cessation is another important one. Monitoring your blood pressure with a cuff at home or with your primary care doctor can be really effective in preventing problems down the road. We'd also recommend undergoing routine screening for things like cholesterol and monitoring your blood sugar.

(19:18): Long-term effects occurring in the lungs tend to be very rare after an auto-transplant, and in most patients, they don't occur at all. The most common lung issues are either side-effects from their chemotherapy treatments, a lung issue called ‘radiation pneumonitis’, or a fairly rare form of toxicity called ‘engraftment syndrome’ that can occur very early after a stem cell transplant.  

(19:57): If these problems have not arisen after six months post-transplant, they probably will not. The main risk factors are having radiation to the chest, receiving chemotherapy like bleomycin – often used for those germ cell or testicular tumors – and carmustine – a form of conditioning chemotherapy in autologous stem cell transplant for patients with lymphoma. Smoking is a risk factor as well.

(20:23): For those patients who do develop lung issues related to transplantation, they are typically monitored with lung function studies and chest CTs, and should be followed by a pulmonologist.

(20:40): Treatments tend to include steroids administered either as a pill or an inhaler. Also, during treatment we keep track of the total amount of these lung-toxic chemotherapies you receive, to ensure you aren’t administered more than the recommended ‘lifetime dose’ of that chemotherapy.  

(21:02): Nerve damage is another form of toxicity that can occur after transplantation. Nerve damage can occur secondary to chemotherapy that was given before the auto-transplant, or from drugs administered during the transplant process as well. There could be other contributing factors, like diabetes or spinal arthritis as well.  

(21:17): Neuropathy is essentially any atypical sensation caused by the treatment or the disease. Most often my patients describe numbness, and it’s usually from chemotherapy. Pain or cold intolerance can also occur.  

(21:28): It's important to note that certain types of neuropathy or nerve issues that occur from chemotherapy can be permanent. A drug used in multiple myeloma – called bortezomib (Velcade) – unfortunately can often cause some neuropathy, and most patients experience it in their feet or hands. While uncommon, myeloma itself can also cause nerve damage, and can sometimes be associated with weakness as well. If you notice any new neuropathy, or changes in your neuropathy, it's important to notify your doctor right away.  

(22:35): If neuropathy or nerve problems arise, your treating doctor needs to be thoughtful about chemotherapy choices in the future. Drugs like gabapentin or pregabalin can help to reduce symptoms of neuropathy. While it doesn’t tend to help treat the numbness, it does help treat the tingling. Other drugs – like duloxetine (Cymbalta) – may be helpful to help people deal with their symptoms of neuropathy as well.  

(23:17): Non-medicinal therapies, like physical therapy, warm foot baths, and avoiding cold exposure and other aggravating sensations can sometimes be helpful to prevent those symptoms. I have had a few patients tell me that wearing compression stockings can be effective, but others find tolerating the stockings difficult due to their neuropathy. Adjunctive therapies like acupuncture can be helpful for many as well.  

(24:03): There are a few contributing factors that can cause sexual health issues to occur after an auto-transplant. Some patients may experience hormonal issues – such as low testosterone or estrogen levels – as a side effect from radiation or chemotherapy. Anxiety or depression is also commonly experienced after transplant in patients and even their partners, and can directly affect sexual health as well. Additionally, things like poorly controlled diabetes can be a physical cause of reduced sexual function.

(24:46): If patients do experience these issues, we can monitor hormone levels and provide replacement if needed. We also want to manage those contributing factors as they arise. Some patients may find it helpful to engage with a sex therapist, or a couples counselor depending on the issues that arise.

(25:18): Let's talk a little bit about fertility issues that may arise after transplantation. Many females become menopausal after transplant, however some women do remain fertile, and it’s important to remember that even if the individual is not having a regular menses, it does not automatically mean that they are infertile.

(25:42): If you are interested in having children after transplantation, there doesn't appear to be a risk to either the mother or the child if the mother has gone through an auto-transplant. And the same holds true for the father. It is possible to conceive after undergoing an auto-transplant, but I do strongly recommend the mother being followed by an OB-GYN who is familiar with the specific toxicities and side effects that can be caused by an auto-transplant. Men can experience fertility issues after transplant as well, but they are more variable.  

(26:27): If it’s possible prior to treatment, we suggest fertility preservation. Ideally, before chemotherapy exposure, women undergo egg harvesting and men can utilize sperm banking. If fertility preservation is not done prior to treatment, a fertility specialist may be beneficial to provide guidance through any issues that may occur.

(26:59): Mental health challenges may arise after transplantation, and can manifest in various ways. Patients may experience loss of interest in old hobbies or activities, impaired sleep, and sometimes even feelings of guilt.

(27:15): Survivor's guilt is a phenomenon that can be a very complex experience after you have recovered from transplant. You may know someone who is also going through the transplantation process who maybe didn't have as good of a course. It’s important to note these emotions are common, and normal, and it’s important to talk with your loved ones and even your healthcare provider if you find yourself feeling those things.

(27:44): There are many strategies you can utilize to help improve your mental health. Engaging in family and community activities, and seeking out spiritual support can all be very impactful. Counseling is also invaluable. There are cancer survivor support groups – both locally and online – that can be very beneficial, and may help provide information and other stories from people who have gone through the same journey that you have. Getting exercise and physical activity is helpful for both the mind and the body, and practicing mindfulness, journaling, and meditation can also be helpful.  

(28:43): Mental health is multifaceted, and therefore takes a multifaceted approach to maintain its well-being. Engaging in one of these activities may be helpful, but will likely not provide you the full support you need. The patients who are going to do and feel their best are those who are utilizing at least two or three of these options, and making them real priorities.

(29:01): Cognitive health can also be impacted by late-effects of an autologous stem cell transplant. These can be issues with brain fog, or difficulty remembering things and completing tasks. Certain factors -- such as age -- can be a predisposing risk factor, and certain medications can make you feel sleepy or impact brain function as well. After transplantation, your appetite and ability to eat a full meal may be reduced, which can lead to dietary deficiencies – such as B12 deficiencies or other organic endocrine problems – that can also contribute to decreased cognitive function. Depression, anxiety, or even impaired sleep cause difficulties as well.

(29:56): In some cases, some time off chemotherapy can help restore and improve cognitive function. Additionally, lab tests to assess vitamin levels or even thyroid functioning could be helpful. Sleep apnea testing and addressing any issues with sleep issues can be helpful, and formal cognitive testing can help identify specific issues as well.

(31:11): To summarize, I want to highlight that most patients do return to their previous level of activity after transplant. I tell all my patients that my goal in taking you through this really intensive therapy is so that you can get back to living a good life. You may or may not be on maintenance chemotherapy afterwards, but we are fighting your cancer, and doing the transplant to restore your health to enable you to live a full life.

(31:44): The best health action that you can take is to maintain regular contact with your primary care provider and your treating hematologist or oncologist. Certain health issues are more common after an autologous stem cell transplant than others, and those things can be scary. Your doctors will be able to guide you through any number of health issues that may arise. Many of these we've discussed may never be a problem for you, but some can make a real impact in your life, so communicate and allow your providers to help you work through any issues. And remember that engaging in healthy behaviors like regular exercise and smoking cessation will have a tremendous impact on your health and well-being as well.

(32:26): I want to highlight a few resources that you can look to for further information. The BMTInfoNet.org, who is sponsoring this symposium, is a great resource. For patients with multiple myeloma, the Multiple Myeloma Research Foundation at theMMRF.org is a great resource. Similarly, the Leukemia & Lymphoma Society at LLS.org is an excellent website for patients with leukemia or lymphoma.

(33:07): Here is the study I mentioned that talked about secondary-cancers:  

Curtis, R. E. M. A., et al (1997). “Solid cancers after bone marrow transplantation.” The New England Journal of Medicine 336(13): 897-904.

Question and Answer

(33:43): [Thom Stewart]: Are N95 masks really enough to make air travel safe? At what point should we start flying?

(33:58): [Dr. Johnathan Lambird]: We recommend patients try to reduce things like air travel for the first six months after transplantation. As I said, the immune system recovery is a slower process, and we recommend all patients using N95 masks for at least the first six months, and then at their discretion. If you're able to make the trip by car, it's probably a better idea as you have more control of who you will be around.

(34:38): The second part of the question is when is it safe to travel? That's a bit of a loaded question. I try to have a conversation with my patient about what they're hoping to travel for. For patients who want to go on a cruise, I advise that they try to do something like that after the first year because they will have completed more of their vaccinations.

(35:09): However, there's also travel that may be less elective. When you need to travel across the country to attend the funeral of a close loved one, I don't want to tell you that you can't do that – even if you're six or seven months out from transplantation. It's not about when you can re-engage in these activities. it’s about the safest manner to engage in activities that you need to engage in.

(35:32): That’s a long answer to a relatively short question, but I think the goal should be to reengage in activities thoughtfully. We want you to enjoy those activities, we just need to do it strategically.

(36:00): [Thom Stewart]: How is younger age defined regarding risk of secondary cancers occurring?

(36:09): [Dr. Johnathan Lambird]: In general, most patients who are proceeding with an autologous stem cell transplant for multiple myeloma are over the age of 60. The average age of patients who have an auto-transplant for lymphoma is going to be younger, because certain lymphomas can occur in younger patients. But I'd consider ‘young’ to be under the age of 40. It's probably more of a continuum though, so I would say somewhere between 40 and 60, and definitely under age 40.

(37:02): [Thom Stewart]: Does what you're sharing apply to people who have had CAR-T cell therapy?

(37:11): [Dr. Johnathan Lambird]: It can. That's what I was trying to highlight in that first slide. There are many similarities, and in some cases, patients thinking about going to CAR-T therapy may have already had an auto-transplant. The chemotherapy dose that's used in CAR-T therapy is generally lower in intensity; however, the side effects of CAR-T are unique and can vary from person to person. There are some side effect similarities, but also many that differ. Survivorship after CAR-T may be its own talk during this conference.

(38:02): [Thom Stewart]: Measles is spreading in my community. I'm still not able to be revaccinated post-transplant. Do N95 masks work for measles and how do we navigate this risk?

(38:22): [Dr. Johnathan Lambird]: Limiting your exposure is the best action that you can take, which definitely includes wearing an N95 mask. Having a small ‘pod’ – or limited list of people that you see and trust – is a great strategy, but sometimes very difficult to actually do. Some of my younger patients still have school-age children at home, so they are being constantly exposed to the community through their kids. I've had patients who will find another place to live for a couple of months after transplantation, but that can be difficult and maybe impossible for some people.  

(39:22): Limiting your exposure, wearing a mask, being extra cautious, and just hunkering down until you’ve hit a year so you can think about getting your MMR vaccine is what I’d recommend. Unfortunately, the measles outbreak is a new threat that we as a medical community haven't had to deal with, so we're still learning the best strategies, but limiting your exposures and taking things like masking very seriously are probably your two best options.

(40:03): [Thom Stewart]: What are the signs of a relapse after stem cell transplant?

(40:16): [Dr. Johnathan Lambird]: Relapse after transplant can take many forms, and it depends on what disease you had a transplant to treat. Sometimes people have an auto-transplant for other things, but some common diseases are multiple myeloma, lymphoma, or for a germ cell tumor.  

(40:37): Relapse after myeloma is typically going to be identified on routine blood work – checking myeloma markers like your M-spike and your Kappa Lambda light chain ratio. Identifying relapse with lymphoma may be identified with a PET scan or on routine blood work that shows changes in blood counts. Those things are typically confirmed by more intensive tests. Sometimes, a bone marrow biopsy is warranted, or a lymph node biopsy if it's a lymphoma. It's specific to the initial cancer or disease that led to transplant.

(41:28): The reason we do maintenance therapy after transplant for multiple myeloma is because the transplant is not a curative therapy. It's an intervention that provides a tremendous amount of disease control, and can help deepen and prolong a response. But the vast majority of patients will have their myeloma come back. I counsel them to be ready for the relapse, and ideally, it's many, many years down the road. Then, we talk about strategies to deal with the relapse when it does occur.

(42:13): [Thom Stewart]: Here's a question that is only a single word: cataracts. It's not clear whether it means ‘Are cataracts a risk factor?’ or whether it means ‘How do you treat them if you have them after transplant?’.  

(42:35): [Dr. Johnathan Lambird]: Part of the treatment for most lymphoma therapy involves prednisone or some other form of steroid, and myeloma therapy requires high doses of steroids as well. There's an increased risk for cataracts after long-term steroid exposure, and this compiles onto the normal risks for cataracts – such as age.

(43:10): Cataracts are something we see in our patient population, and typically a referral to an ophthalmologist, and cataract removal surgery with an eye surgeon, benefits them tremendously. If they do occur, that's a problem that we can address surgically fairly well and fairly effectively. We're aware that it can happen and we monitor for it.

(43:38): [Thom Stewart]: Why are heart issues, bone issues and other cancers more common after autologous stem cell transplant?

(43:51): [Dr. Johnathan Lambird]: We assume that it has to do with the exposure to high doses of chemotherapy. The chemotherapy that you receive with the transplantation tends to be very, very intensive. The cells in your body that are going to be the most resistant to chemotherapy and treatment are going to be those that are the most capable of becoming cancer later. They are able to survive when the other cells are not. This theory can’t easily be tested, but secondary bone marrow cancer after treatment might be because cells in the bone marrow survive the chemotherapy, and can grow to become a new bone marrow cancer like AML or MDS.  

(44:53): Other cancers like lung cancer or head and neck cancer probably have a similar explanation. That’s why it’s important to control the risk factors that we can – like wearing sunscreen and limiting sun exposure to reduce your risk of skin cancer, and reducing smoke exposure or smoking cessation to reduce the risk of head, neck or other cancers.

(45:24): Regarding heart issues, some chemotherapy that we use – such as melphalan – can sometimes cause issues like atrial fibrillation. It's a combination of factors, but generally it’s because the chemotherapy doesn't just go to where the cancer is. It goes to the heart, the lungs, the kidneys, the liver, the brain – and there's a potential for damage to each of those sites.

(45:53): [Thom Stewart]: I just had my stem cell transplant in January and I'm very concerned about secondary cancers. What are some things that I can do to reduce that potential?

(46:12): [Dr. Johnathan Lambird]: The best thing you can do is live a healthy lifestyle. I'm going to guess this patient's probably not smoking or using chewing tobacco, but cutting out lifestyle choices that predispose them to cancer, and maintaining a healthy lifestyle.

(46:33): Some studies indicate that engaging in physical activity, or daily stretching and other things can reduce cancer risks. Testing that is hard to replicate in large population-based studies, but I think that there's merit to those things.

(46:46): There are dietary changes – like reducing sugar and exposure to high fructose corn syrup – that are modifiable risk factors, probably not supported strongly in the literature, but healthy things to do anyway. Whether you're doing it in the name of general health promotion or in cancer risk reduction, they're beneficial.

(47:19): Outside of that, the best thing is to stay consistent with routine cancer screenings with your primary care doctor – colonoscopies, mammograms, pap smears, prostate cancer screenings. You’d want to speak with your doctor to identify what your specific needs are. I want to reemphasize that 93% of people don't develop a secondary cancer after their transplantation. The vast majority of people don't, but the cancer risk is slightly higher than the general population, so it's important to get those screenings and to engage in those activities. But remember and take solace in the fact that the vast majority of people don't develop a secondary cancer after transplant.

(48:16): [Thom Stewart]: I'm almost three years post auto-transplant with a diagnosis of multiple myeloma in October of 2021. My immunoglobulin levels are still low and since I've had a few IVIG transfusions to boost my immunity, is this really my only health challenge right now? Am I always going to be immunocompromised or will this gradually improve?

(48:53): [Dr. Johnathan Lambird]: If you're three years out, it may be that your immune system is going to be low on immunoglobulins and IVIG replacements are going to be needed. Patients with multiple myeloma – particularly those who are on daratumumab – tend to more often be ‘hypogammaglobulinemic’ – meaning they have low immunoglobulin levels.

(49:37): If you're this far out, it's likely going to persist until something changes. I wouldn't routinely recommend that my patients stop maintenance chemotherapy to improve their immunoglobulin levels, but some patients three years post-transplant may be stopping daratumumab anyways. That's something to talk to your doctor about. Perhaps it’s not a fair assumption, but I’m assuming your immune system may continue to be somewhat limited from here on out.

(50:16): [Thom Stewart]: I am 10 months post autologous stem cell transplant, still dealing with anemia. Is this common? Peripheral neuropathy in my feet that started well before my multiple myeloma diagnosis is still a problem as well. Can this be reversed?

(50:40): [Dr. Johnathan Lambird]: Regarding the first question about the duration of anemia after transplantation, it's very uncommon to be in a place where you're still requiring blood transfusions after stem cell transplantation. That's quite unusual. Or you can be anemic, but not need a blood transfusion. It depends on the extent of the anemia – a hemoglobin level of 11 or 12 after transplantation is different from a hemoglobin level of 8.5. I would expect most of my patients to have a hemoglobin level that's at least an 11 and, ideally, return to normal range.

(51:22): If it's not in the normal range, then it's fair to investigate reasons why – like checking an iron panel, a B12 level, and potentially other vitamin levels to see if there are deficiencies. Especially 10 months out, dietary deficiencies could certainly contribute.

(51:40): In some cases, patients may benefit from having a bone marrow biopsy done, but that would depend on the overall clinical picture – such as the hemoglobin levels, if there are potentially other alternative explanations, etc. That’s the strategy I would take to further evaluate that issue.

(52:45): [Thom Stewart]: Is there a standard revaccination schedule?

(52:51): [Dr. Johnathan Lambird]: Believe it or not, there's not a standardized schedule. There's a standardized list of vaccines that we use – which I provided earlier in the talk – but not a schedule. Vaccine schedules will vary somewhat from location to location, and there is some flexibility to it depending on how far away a patient lives from the center and other factors like that.  

(53:49): For the most part, we try to have our vaccines completed by a year and a half out from transplant. The only vaccine we gave at the two-year mark was the MMR, and now we're trying to move that up to one year out for most of our patients.

(54:14): [Thom Stewart]: Can peripheral neuropathy in feet, that started well before the multiple myeloma diagnosis, be reversed?

(54:39): [Dr. Johnathan Lambird]: Unfortunately, multiple myeloma treatment – specifically the shot in the belly, bortezomib (Velcade), – is a drug famous for causing neuropathy. If your neuropathy was present before the multiple myeloma diagnosis, it may have been driven by the presence of the myeloma. That certainly can happen specifically for IgM subtypes. However, what you may be experiencing may be permanent – especially if it is Velcade induced. That's when we shift our focus to management strategies. We may not be able to reverse it, but can we reduce the symptoms? Can we use things like gabapentin to make the pins and needles sensation less? Can we engage in some adjunctive therapies like acupuncture?

(55:50) [Thom Stewart]: What can be done if energy levels don't return to normal?

(56:02): [Dr. Johnathan Lambird]: First, I would notify the doctor who's treating you. Many of my patients do notice decreased energy levels but it’s also important to keep perspective. Patients being treated for multiple myeloma usually get an average of four to six months of chemotherapy to prepare them for the autologous stem cell transplant. Then, they get the transplant, and spend the next six months to a year recovering. Not only has time passed, and you have aged, but chemotherapy also ages you, so your baseline energy levels may have changed. Also, patients with myeloma are often on maintenance chemotherapy, and drugs like Revlimid can cause fatigue as well.

(57:30): If fatigue is a problem, then we need to discuss strategies about things we can do. At our center, we have our patients do three weeks of therapy on Revlimid, then take a week off. Some centers do continuous dosing, which is fine, but attempting a week off and assessing how you feel might be beneficial, and might help clarify if it’s the transplant or maintenance chemo causing the fatigue. If it seems to be maintenance, then we talk about the risks and the benefits of dose reductions. If it really doesn't seem to be the maintenance therapy, then we look for other contributing factors.  

(58:41): There are many ways to investigate fatigue as a symptom, and there are many things that can cause fatigue. It's hard to have a single answer without the context of your chart. But the first thing to do is discuss these symptoms with your doctor.

(58:59): [Thom Stewart]: Closing. Thank you, Dr. Lambird. On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Lambird for a very helpful presentation. And thank you, the audience, for your excellent questions. Please contact BMT InfoNet if we can help you in any way. We hope you enjoy the rest of the symposium.