Infections after Transplant

Stem cell transplant recipients have a high risk of of developing an infections, particularly during the first six months. Learn how to prevent and treat infections after transplant

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Infections After Transplant

Monday, May 2, 2022

Presenter: Shivan Shah MD, Onco-Transplant Infectious Disease Specialist, Center for Cell and Gene Therapy at Houston Methodist Hospital, Houston, Texas.            

Presentation is 32 minutes long with 24 minutes of Q & A.

Summary: The chemotherapy and/or radiation given to patients before a stem cell transplant compromise immunity and leave patients vulnerable to infections. This presentation describes major infection risks and effective responses to them. 

Many thanks to Takeda Pharmaceutical Company whose support, in part, made this presentation possible.

Highlights: 

  • Most infections occur within the first 180 days after transplant.
  • Patients should be re-vaccinated after transplant with non-live vaccines. Family members should also have up-to-date vaccinations to avoid spreading disease to the transplant recipient
  • Stem cell transplant recipients should be vaccinated against COVID. Problems such as myocarditis and blood clots are more likely to arise from COVID itself, than the vaccine.

Key Points:

(03:34): The risk of infection after transplant is higher for patients who are transplanted with donor cells (allogeneic transplant) than in those transplanted with their own cells (autologous transplant).

(08:17): The bacterial infection seen most often after transplant is strep pneumonia.  Other bacterial infections seen after transplant are strep viridans, Hemophilus Influenza B (Hib) and Bordetella pertussis.

(10:13): CMV, HSV and VZV are common viruses that are often dormant in a person’s body and can become active when the immune system is suppressed.

(14:53): Bacterial infections can occur as a result of eating contaminated food. Transplant recipients should avoid unpasteurized food and eat cooked food, rather than raw foods, until their immune system recovers

(18:08): People should minimize contact with pets during the first six months after transplant, and particularly avoid cleaning up urine or fecal matter.

(19:15): Develop a plan to avoid picking up an infection from children during the first six months after transplant

(20:18): Maintaining good oral health and regular dental exams can prevent many infections.

(21:44): Good foot care is important to avoid fungal diseases.

(28:36): Monoclonal antibodies and remdesivir are effective treatments for patients with COVID.

(30:29): Hydroxychloroquine and Ivermectin are not effective treatments for COVID.

Transcript of Presentation:

(00:01): [Marla O'Keefe] Introduction. Hi, my name is Marla O'Keefe. Welcome to the workshop Infections after Transplant. I'd like to thank Takeda Pharmaceutical Company whose support helped to make this workshop possible.

(00:14): Speaker Introduction. It is my pleasure to introduce Dr. Shivan Shah. Dr. Shah is an onco-transplant infectious disease physician at Houston Methodist Hospital, where he works with the oncology and stem cell transplant teams to treat patients who have various oncology or transplant-related infections. Dr. Shah's clinical interests include onco-transplant infections, infections in leukemia and lymphoma, respiratory infections, and travel medicine. Please join me in welcoming Dr. Shah.

(00:49): [Dr. Shivan Shah] Overview of Talk.  Hello, this is Dr. Shivan Shah, one of the onco-transplant infectious disease physician of Houston Methodist Hospital. Today, I just want to briefly talk about these infections after transplant. It's a pretty wide area and a lot of questions, especially in today's world we're having with infections. So go ahead.

(01:15): No disclosures for me at this time. So today's objectives are we want to Shah what's the importance of having an infectious disease consultation before and after a stem cell transplant. Also, we'll go over risk factors for developing infections. Then, we'll talk about what are ways we can minimize risk. There're various ways. And also, that will include what are things that we need to do for ongoing care after a transplant. And lastly, we'll briefly touch on COVID-19. It'll just be a brief point on a few slides about it.

(01:51): So infectious disease and our stem cell population, it's a fairly recent thing that we've been involved in. Previous to this, infectious disease was really known as like an HIV type of consultation, or HIV was the last large epidemic or pandemic we had in the States. But now, because of the increased amount of bone marrow transplant or stem cell patients we're seeing, we're also seeing a lot of opportunistic infections. And if not diagnosed early enough, we can see a higher mortality. Basically, we're here to help you as a patient and families to navigate through the world of these infections. Infections will always be here. They'll never go away, but with some help we can hopefully get them cured.

(02:45): The number and types of transplants have been increasing in recent years which also increases the chance of infection. This is just one of the graphs that we have, showing the number of transplants that have been slowly increasing throughout the year in the US. This just goes up to 2015. However, it's gone up much higher in past years, except for the past two years where COVID started, where unfortunately, it was more difficult to start doing transplants.

(03:12): Another side showing the different types of transplants, their increasing amount. Basically, just wanted to show that the more transplants we do, the more chances of infections we have, and the more times we will likely be consulted. And unfortunately, you may have to see us for an infection.

(03:34): The risk of infection after transplant in higher for patients who are transplanted with donor cells (allogeneic transplant) than in those transplanted with their own cells (autologous transplant). So now we'll go into risk factors for infection. The biggest risk factor that we have is the type of transplant. The type of transplant that you get usually will [be] determined [by] the days to engraftment. Days to engraftment are, of course, when the blood counts recover, that's when you're engrafted. And the time that you aren't engrafted is the highest risk of getting any type of infection.

(04:05): Autologous transplants, where we use the patient's own stem cells, the engraftment occurs much earlier, before 10 days usually. Allogeneic stem cells, so donor cells, will usually take between 14 to 30 days and even longer. These are the average times, but they're always outliers for both. And the longer time you're without white blood cells, the higher risk you have for more infection.

(04:43): Most infections occur within the first 180 days after transplant. The next slide that we have is just a graph showing phases of predictable immune suppression and associated opportunistic infections. It's a pretty large slide, but I just wanted to show that before day 180, so within the six-month mark, that's where you get most of your infections. It is the highest risk of opportunistic infections and also contagious infections you can get from family members or if you're outside somewhere. We usually tell our patients at the six-month time, after that, it's a little safer, if they want to do something. But before that, it gets a little risky. You can get infection varying from fungal, bacterial, viral, or parasitic infections. However, even after six months, there is a risk factor, but the immunosuppression is much less. So it's less risky.

(05:47): Other risk factors may be unique to each patient so a comprehensive social and medical history may be required. Other risk factors we have is that basically, when an infectious disease physician is interviewing you, we want to find out all about your life. You'll have an infectious disease physician come in the room and discuss your hobbies, where you were born, profession, vaccine status, sexual history, pets and animals that you own and are in contact with, and then history of infections. What this helps us formulate is what are your risk factors. We've had patients that would be carpentry enthusiasts. They would buy wood from Papua New Guinea, and they developed a fungal infection from the wood from Papua New Guinea. So even just the slightest clue can help us figure out what type of infection you have. And our transplant patients are the trickiest because they don't present with infections like the rest of the population does. They'll maybe just have a fever, but they won't present with any other symptoms. So it's our job to help navigate through this and diagnose what's going on.

(06:59): Infection risk can be reduced with pre-transplant screening and post-transplant prophylactic medications and vaccines. Steps that we can use to reduce the risk of transplant-related infections. Usually pre-transplant, again, an evaluation by an infectious disease doctor with some pre-transplant labs and clinical history. Typically, our pre-transplant labs are varying from just serology testing and testing for other types of maybe enteric parasites that, especially if you traveled, we may want to know. Post-transplant, we want to make sure you're on the right prophylactic anti-infectives.

You'll see when you get a transplant, you'll be on some antivirals and some antibacterials for a given time, especially in that six-month time to prevent any infections or most infections from happening. However, there are always breakthroughs and people can develop infections. Other things that we do post-transplant are vaccines, so that's one thing we'll touch on that in a little bit. The risk of disease and death is less in patients who actually follow these recommendations, take their medications, and you'll see drastic changes in you being admitted to the hospital if you're compliant with the medication.

(08:17): The bacterial infection seen most often after transplant is strep pneumonia.  Other potential bacterial infections include strep viridans, Hemophilus Influenza B (Hib) and Bordetella pertussis.

The most common bacterial etiologies that we see in our patients that get transplant the most common bacterial infection seen in transplant patients is strep pneumonia. Number one, what we've seen is usually strep pneumonia. It is a bacteria that actually causes pneumonia, there is a vaccine for it, and it's one of the ones that we can prevent, especially with a vaccination. It is, however, treatable with antibiotics. It's spread through pneumonia - person to person can get it, unfortunately -- but it is not as contagious as a viral infection. You have to be in very close contact.

Strep viridans or streptococci typically is, you could see it as a blood-borne bacteria. It usually does happen by the drying up of your mucosal lining of your mouth, and it can cause a bloodstream infection. The way we treat that or prevent it is usually a prophylactic antibiotic after your transplant and making sure you have good oral care.

(09:23): Hib, which is Hemophilus influenzae B, there's a vaccine for it. We've seen it less because of the vaccine, but again, prophylactic antibiotics help out with it. And lastly, Bordetella pertussis is one of the major ones. It's a droplet type of infectious disease. The treatment is an antibiotic. However, again, it's preventable with the vaccine. We get it with the Tdap vaccine, which you can get as a booster every so often in clinic.

(10:01): Basically, the viral infections that we have CMV, HSV, and VZV, all of these, we test beforehand on you, we do a serology testing.

(10:13): CMV, HSV and VZV are common viruses that are dormant in many people and can become active when a patient’s immune system is suppressed. CMV is a disease that many of the world's population already have in their body, but it doesn't present itself till you end up having immunosuppression. So after a transplant, it is very, very important that your physician or primary doctor monitors this, especially if you're IgG positive prior to transplant. It's not really contagious, per se, in the matter of that if you have it, you'll spread it to everyone. Because again, most of the world population already has it. Prophylaxis is with the medication called valganciclovir. We also have other medications now called letermovir and maribavir that are just released, and they work very well against preventing this infection.

(11:02): HSV, very common, cold sores, genital herpes as well. The best way of preventing is a prophylaxis with Valtrex. It's another antiviral, very commonly.

(11:15): And lastly, VZV. VZV is zoster or shingles, we call it. We can test for VZV IgG, but if anyone with the history of chickenpox will likely have this already in their system and they can reactivate after a transplant. This is one that we use contact and airborne precaution. So if you have a large shingles outbreak on your body, those vesicles that form on their can burst, then actually it can be airborne and it can become contagious to the person nearby you. Basically, the best prevention for this is getting the vaccine. And there is a new vaccine now that we can use for our transplant people, which I will talk about shortly.

(12:02): So vaccinations pre- and post-transplant. So this is a list of transplants. As you could see, most of them you could give after six months. The pneumonia vaccine, the PCV 13, you can do after three months. But the PCV 23, which is a broader one that you will give usually is 12 months after transplant. Influenza, you could give four months after transplant. However, during times of major epidemics or pandemics, it might be required to give it a little sooner. And the recombinant zoster vaccine, we want to do 50 to 70 days post-transplant, and then a second dose we could do about two months later. These are all in protocol. We have many eyes looking to make sure you have all these done. But most of them, we'll give after six months.

(13:02): Live vaccines should be avoided after transplant until the patient's immune system recovers. Now, there's a list of contraindicated vaccines. I write this and we'll talk a little bit about it right now. So any live vaccine, it can be very detrimental early on. Influenza, we have a non-live vaccine, so we prefer to give that.

(13:20): MMR, now recently and this is current news, measles has gone up in very, very high amounts across the world. And there are many studies that during times of pandemics or epidemics, it is okay to give it earlier. Typically, all these contraindicated vaccines, if needed to give, you give after two years; however, in times of epidemics or pandemics, you can give it after a year. Earlier than a year, it may be risky and cause unfortunately some reaction or reactivation of a virus and infection. So it is something to be aware of.

(14:08): Family members’ vaccinations should be up to date to reduce the risk of the patient getting an infection, including COVID So a big problem that we're seeing recently is getting family members vaccinated. During the COVID pandemic, it was very difficult because people had to isolate. We had to make sure we got vaccines to everyone. So it is imperative that your family is given routine vaccinations. If they want to keep you safe. We call it cocooning the patient, keeping the patient safe, especially in the first year, it is very important. During COVID pandemic especially, we want to make sure that this is done. COVID is very contagious.

(14:47): Lifestyle changes, we'll go over that to help minimize risk of infections.

(14:53): Bacterial infections from contaminated food are common. Bacterial infections are a very common thing we see. As you can see, I've listed a few, Campylobacter, Listeria, E. coli, Salmonella, Shigella, Vibrio, and Yersinia. These are all food-borne pathogens that we can get. And they can actually cause disseminated infections in a few of these. You'd be surprised, there will be dietary recommendations and restrictions that you'll have, but certain things will be a big no-no.

(15:20): Transplant recipients should avoid unpasteurized food and eat cooked food, rather than raw foods, until their immune system recovers. One of the big things, I'll say, is anything unpasteurized - definitely would avoid. This is not to scare you. This is not to say, you can never have a salad again, of course, but be aware there are outbreaks in packaged salads. Soft cheeses can also be very risky. Poultry, you have to cook it very thoroughly, make sure you wash your hands and everything. Salmonella, being around reptiles, is just one of the clinical clues we always have. Some people own pet turtles and things, and you can actually develop a disseminated Salmonella infection from that. So biggest thing is to make sure anytime you're going to have these types of foods, it's usually better to eat warm, cooked food versus cold food and avoid raw foods. That's the biggest thing.

(16:17): Fecal matter can be found on food. Yeah. So food contamination can occur in many forms, raw and cooked meals. Unfortunately, we will see fecal matter from animals. It's farm food. It'll happen. And then unpasteurized products, including orange juice, so you got to be careful. Pasteurization is a form of helping kill off bacteria. It's a good thing. We want that to happen. So you make sure you drink pasteurized only things. Especially, if you're traveling, it's very difficult to see what is a clean drink versus a not clean drink. Raw honey, deli meats, raw shellfish again are also problems. A rule of thumb, like I said, cooked food is always better than cold food.

(17:03): Frequent hand washing is important to minimize viral risks from food or other sources. Viruses and parasites in food. So many viruses can cause chronic illness. A big one, I would say, is called norovirus. People can have chronic norovirus. So they're not really related to foods a lot. A lot of times it can be related to other items and it could be contagious from person to person and it's just fecal-oral route. So it can be on from fecal matter from animals or even humans unfortunately, it can be contaminating things. So wash your hands, wash your hands, and wash your hands.

(17:34): Stick to bottled water and cooked foods when traveling outside the USA. Parasites are very uncommon in the USA. However, if you're traveling around the world, you can definitely get it. They are not unheard of over here, but these things as an ID physician, we could test for and figure out. When you're traveling outside the country, stick to bottled water and hot foods. Never use ice from the street. Unfortunately, people will go to a cafe and order a juice or a soda and get ice and unfortunately, they'll become ill. And I've seen many, many infections because of this.

(18:08): People should minimize contact with pets during the first six months after transplant. Pets, animals and children. So our pets and other animals, our pets are very dependent. We all love our dogs and cats, and they're very dependent on us. The first six months after transplant is very, very important to have a social network to help... People to help you out with the animal that you have. You should not be cleaning up their feces or urine as I discussed before. And if you have any exotic animals, now by exotic animals, birds, reptiles, even snakes, things like that, you could develop some infections that are very bad. They can be parasitic, fungal, things like that. I would avoid them completely. The biggest thing is get help and try not to take care of them on your own, of course. Definitely, do not need to get rid of them completely, but it's very important to make sure that you're clean and you aren't taking care of their fecal matter on your own.

(19:15): Caution around children should be practiced including masking and isolation where feasible. Children. If you have children, young children, and you need to get a bone marrow transplant, just before a transplant happens, there should be a plan within the household. Kids, they will get many illnesses, especially viral illnesses at school, hanging around other kids. They go to Chuck E. Cheese, they'll pick up something. They will not always present with symptoms. They're very mild symptoms, they might just get a runny nose one day or one time fever. I'm not saying to avoid our children, of course, but you should consider masking and other precautions, somewhat isolating if you need to, especially within the first six months. Like I discussed, first six months are very crucial. Consider distancing during those times if you want your mask off and then, hand washing for everyone in the household, not just yourself, a big must.

(20:12): Routine care. What you do after a transplant, what is routine care to help avoid certain infections?

(20:18): Maintaining good oral health and regular dental exams can prevent many infections. So oral health, big major player. I get a lot of consults in the hospital regarding mucositis or ulcers in the mouth and things like that. After a transplant, the mucosa can become extremely dry. This is called xerostomia, you'll hear us talk about that. It's because of low saliva flow. When you have low saliva flow, the moisture's gone and oral bacterial flora can sneak into bad areas of the teeth, inside the teeth to look for that flora. They'll die out otherwise, if it's too dry in your mouth. You'll get cavities. You'll get dental accesses. And in a patient with transplant, these can be very, very indolent or very slow growing so that it won't present till a while, and people can miss it.

(21:05): And then, it can get to the point where it infects the upper bone and it may require surgery. So we want to prevent all that. The best way of doing that is undergoing an evaluation with your dentist that you have or developing a rapport with the dentist. Typically, we say 6 months to 12 months, going to them to making sure everything's okay, just routine care. If you have any mucositis or ulcers in the mouth or pain, we prescribe salt and baking soda rinse, which is essentially like a magic mouthwash as well. And it'll help relieve those symptoms and it'll help develop some moisture in the mouth as well.

(21:44): Good foot care is important to avoid fungal diseases. Foot care. So feet, unfortunately, are one of the most ignored parts of the body. People can miss it. People do not like... Do not want the doc... They always wear socks. They don't want the doctor to look at their feet. However, feet can develop a lot of cuts and cracks, which can lead to infections. Transplant patients are more prone to fungal diseases, especially fungal infections of the feet. It's commonly known as athlete's foot, but there are other types of fungus that we can see on the feet, especially in the nail bed. It is our job as infectious disease physicians to make sure we monitor your feet too. When you come in, if you develop fever, first thing I do is look at the feet. Other areas too that we see indolent infections, feet, mouth, and even the rectal area, the buttocks area. So you'll see an infectious disease doctor, make sure he is looking through all those, at least the initial round, whenever we see you for a fever or such.

(22:42): If these aren't taken care of early on, they can develop into systemic infections. And I've seen a foot infection cause an infection of the eye because the fungus traveled from the foot to the bloodstream. And if we catch it early on, we can take care of it early on and make sure everything's okay. So it's very important for patients and their families to make sure they're looking at their feet and nothing new is popping up. They're not having pain. Try not to ignore it. Also, make sure you go see a podiatrist.

(23:15): COVID is an ongoing concern and numbers may be creeping up again. And the last part, we'll briefly talk about COVID-19. There is another seminar for this, I'm aware, but this will be just a short talk about it. So past two years, this was an image that we took off of Google, it just had their account in the US. So we are heading into May now and you know, luckily the numbers are down right now. However, they are starting to creep back up, so it's something we need to stay vigilant about.

(23:48): What do you know about COVID-19? Or what do I know about COVID-19? We know it's highly contagious. Vaccines, do they help? And if we get it, how we could treat it? So these are things that we're going to discuss.

(23:59): Early strains of COVID were less contagious; newer strains are much more contagious. COVID-19. So we use a term called R naught. So that R zero that you see down there, it's called R naught. It's a value that we give to see how contagious it is. Now, this isn't fully up to date, but I'll talk about the newer variants while we go over this graph. The original strain, as you can see, it's one person can infect three people. The 1918 flu or Ebola, it's one person can infect two people. Now, as we progressed forward, we started seeing the delta strain. It started getting a little more contagious. So one would infect seven people. Going over towards the complete right side, we see measles, which is regarded as an infectious disease as one of the most contagious viruses out there, and it can be very deadly. And as you could see, it infects many people, one infects 18 people.

(24:56): What we're seeing, the Omicron variant was, between that time, it was between 12 and 18 people. So Omicron was extremely, extremely contagious. We were seeing patients filling up our hospitals during the time of the initial Omicron and infected a wide variety of people. Unfortunately, transplant people ended up becoming a little sicker when I was seeing them, but we had some treatments which I will go over next, but it's very important to know that we could still develop another variant that can be just as contagious and may invade our natural immunity we have or vaccinated immunity.

(25:40): Stem cell recipients have had good responses to the Pfizer vaccine and boosters. The vaccines for COVID. This is just a study that was early on. We showed that there was a higher response rate for stem cell transplant patients and a good response by those who got the two doses of the Pfizer mRNA. Now, we're in this position of multiple boosters. The third booster showed positive effect, and the fourth booster, there are studies that showed that it's beneficial as well, especially just in our immunocompromised.

(26:08): Myocarditis has been a concern but the vaccine actually lowers the risk of myocarditis when compared to unvaccinated patients. We have to weigh the risk and benefits of the side effects. And I'll briefly go over some of the side effects that people have been worried about right now. So the number one, one that I've seen and heard about is myocarditis. People get very scared about this. What we do know about this myocarditis, it was found in the very young population, the teens in fact. And what we do know, as well, is myocarditis was actually found more in patients who developed COVID-19 or who got COVID-19 versus the patients who got the vaccine. So the vaccines actually lowered the risk of myocarditis versus increasing it.

(26:48): Clots are another concern but are more likely to arise from COVID itself than from the vaccine. Clots were another thing that people have been scared about, but we do know after many patients, that clots form likely from the inflammatory reaction of the COVID virus and not the vaccine. We saw that less clots were found in the vaccinated population. So that was very important to know, and it calms the nerves of many people, many patients that I had.

(27:19): There are several medications for stem cell patients who develop COVID but it is crucial to discuss potential side effects and drug interactions before starting them. Treatments for our stem cell patients who develop COVID. So this is ever ongoing changing. I have to get an update every week regarding this. So currently, we've developed new oral medications - the paxlovid, molnupiravir. And paxlovid just became a little more available. Paxlovid is also one of the medications that has a lot of side effects or drug-drug interactions. It is highly important you discuss this with your primary doctor or your transplant doctor, or even your infectious disease doctor, to make sure it's not interacting with your medications. If you're on immunosuppressive medications for GVHD, or things like that, it can interact with them and cause toxicity of those medications. So very important to discuss it. Do not take it without consulting with your physician first. They work pretty effectively for preventing progression. However, patients who get COVID-19 that are still in the pre-engraftment period or highly immunosuppressed on steroids or GVHD medication, they can develop longer COVID shedding and it may not help out with that.

(28:36): Monoclonal antibodies are highly recommended for transplant patients with COVID. The monoclonal antibodies, we've gotten pretty much a new one for every variant because the old ones don't work for the current variant, so we have to continue with newer and newer ones. They are a one-time infusion. They work pretty effectively in preventing severe progression of COVID. Many hospitals, at our hospital too, we see this happening. We see that we can give it pretty easily outpatient, preventing the patient from having to be admitted to the hospital. So it's something that your local hospital should have, and you should be able to get referred to, especially being a stem cell transplant patient. There're certain qualifications, age, obesity, but being a stem cell patient is one of the qualifications to receive it, and I definitely recommend that as one of the first lines for our transplant individuals.

(29:31): Remdesivir is an effective antiviral medication. Remdesivir is our IV formulation of the antiviral that we have. We use it in the hospital. There was a new study that was done showing three days of it for mild COVID should be enough. However, it's very difficult to know if we need a longer duration in our stem cell transplant patients who develop COVID, there is no prophylaxis with it unfortunately. It's usually just for treatment. So we want to make sure that if you develop worsening COVID, that's something you should receive and it should help out with it.

(30:09): Other medications that I didn't really show on here right now; steroids is one if you develop severe COVID. However, many of our stem cell patients develop GVHD and they're already on steroids, so we may need to increase those steroids if they're developing pneumonia from COVID.

(30:29): Hydroxychloroquine and Ivermectin are not effective against COVID. Some older medications I've been studying that do now work; hydroxychloroquine, it's been very studied now. A lot of clinical trials have actually been done now shows that there's no benefit.

(30:42): Ivermectin l is another one. I know there's been a lot of news about it, but it just does not show any benefit. Azithromycin as an antibiotic did not show any benefit as well. And convalescent plasma, initially there was some benefit to it, but the monoclonal antibodies work much better.

(30:58): Even the effective medications against COVID can have side effects so consult with your physician with any concerns or questions. What I do want to convey is, all these medications will have side effects and even ivermectin and hydroxychloroquine, they have their side effects. They can cause heart arrhythmias. Ivermectin could cause a lot of diarrhea and neurotoxicity. So be careful whenever you take. Consult with your physicians, transplant team, and your infectious disease physician if you have any questions about this.

(31:24): COVID will continue to evolve as will appropriate precautions and treatments. The future of COVID. Just a brief slide. It's going to take a lot of changes, still, to help out with it. Still trying to get the vaccine out, coming out with a newer vaccine that covers all the COVID variants, so we don't need to continue with many different boosters and such. Adaptive immunity SARS COVID virus, which we're in the phase of getting to, its turning into this herd immunity/we're understanding that we may be out of the pandemic phase of COVID and into an endemic phase, we may get seasonal variations of this. Strict policy changes, not to say, it needs to be quarantined all the time, but maybe some early pandemic responses for future pandemics, because just as a warning, this will not be the last pandemic in your lifetime. Likely we'll see more in the future, unfortunately. So that is the end of my presentation right now. We'll start the question.

Question and Answer Session

(32:27) [Marla O'Keefe] Thank you, Dr. Shah, for that excellent presentation. We will now take some questions. First question regarding the bacterial infections: Do the recommendations regarding cooked foods primarily apply to the first six months post-transplant, first year or permanently?

(32:55): [Dr. Shivan Shah] Good question. So what I will say is the highest risk you have is within that first year. I recommend at least in that first six months cook hot foods. However, if you want to eat some cold foods like cold salads and things like that after the six-month mark, that is fine. It also depends on the type of transplant you got as well and how long you were engrafted, how long it took you doing graft. Permanently, usually things aren't that permanent. However, just as a caveat to that, anytime you eat raw foods, so raw oysters, beef tartare, things like that, even if you're not immunosuppressed, you have a risk of catching infection, but if you are immunosuppressed, it is a higher risk. Again, if you're traveling outside the country, it's better safe than sorry. If you know it's a reputable restaurant or you're cooking at home and you wanted something like that, then it's a little safer, of course, but you have to be a little careful. And even for myself, I'm not immunosuppress, but I tend to, if I'm traveling around, I make sure I stick to hot foods more than the cold foods.

(34:10): [Marla O'Keefe] Thank you. Next question. I have had both an auto and an allo transplant. In the past five years, I've had four blood infections, pneumonia twice, lung infections, and a brain infection of listeria. Is it possible that my immune system was suppressed too much in an effort to manage my chronic GVHD?

(34:35): [Dr. Shivan Shah] Yeah. Good question. Basically, because of your chronic GVHD, the risk is, and since you've had both types of transplants in the past year, listeria is a known pathogen to cause these types of infections, and it is very difficult to diagnose a lot of times. It takes a little bit of effort, imaging, and Lumbar punctures to get done. If your GVHD wasn't suppressed using immunosuppressives, then you would have other problems going on too. You could have gotten a lot of issues regarding your gut, your liver, even respiratory GVHD that could lead to other problems. It's a seesaw unfortunately, so we have to balance your risk of infection versus your risk of getting GVHD complications. What we consider in this, if it's listeria or some other bacteria, sometimes we just put you on prophylaxis for life, with an antibiotic to make sure it doesn't break through on there, but again, you can always develop another type of infection.

(35:48): [Marla O'Keefe] Thank you. If you are more than two years post-transplant, but still on low dose tacrolimus 1.5 mg, can you get the live vaccines? Second part of the question is also, do you still need the antibiotic and antivirals?

(36:07): [Dr. Shivan Shah] Good question. The live vaccine, it just depends on which live vaccine. This is going to be something to discuss. Typically, if you're on tacrolimus and you're on for GVHD, we usually try to avoid the live vaccines. Now, we're getting a lot more of the inactive vaccines that we can use and like for shingles vaccines, the Shingrix, we can use that now to prevent shingles. But there are certain ones that we have to avoid, because the risk is you can actually develop the infection itself when you get it. Now, if you're not very immunosuppressed, if it's a very low dose, there's a risk and benefit situation, but most of the times we try to avoid that.

(36:51): And the second part of the question with the antivirals and the antibiotics, this depends also on your history of infection. Now, if you're a high-risk individual with CMV or things like that, we may need to continue your antiviral; or if you have a history of herpes, you may need the other antiviral, the Valtrex. A history of recurrent infections with bacteria, then you need to be on the antibiotics, still. Typically, after one year, we avoid the antibiotic, but with an antiviral, and if you're on tacrolimus, we will continue your antiviral. There are some antibiotics we use to prevent fungal infections, but like PJP, which you're on Bactrim for usually, but we usually give that to prevent that infection now. Again, it's the best choices to discuss with your physician and regarding these questions, because they'll know your case and every case will be individualized.

(37:56): [Marla O'Keefe] Thank you. This is a question about bottled water. Should people look for distilled, spring, or something else, or does it matter?

(38:06): [Dr. Shivan Shah] Typically, that doesn't matter as long as it's bottled. You got to be careful in certain countries and actually around the world, you can find bottled water that's not really bottled. So you got to make sure it's a truly bottled water that was packaged and not packaged by them. They can reseal and recycle water bottles all the time. So just be careful with that, but it doesn't matter which type of water it is.

(38:29): [Marla O'Keefe] Okay. If two shingle vaccines were given while on immunosuppressants, are they effective on tacrolimus and Jakafi?

(38:41): [Dr. Shivan Shah] Yes, they can be effective. However, there is a risk that it's less effective. Now the benefit of re-dosing again, there may not be, especially if you're still on your tacrolimus and Jakafi, but there is effectiveness. Any vaccine will still have effectiveness. It just may not be as high as a person who is immunocompetent or less immunosuppressed.

(39:12): [Marla O'Keefe] Thank you. I am 100 days post auto transplant. Do you recommend avoiding air travel until I am six months post-transplant? I am 65 years old.

(39:26): [Dr. Shivan Shah] If it's air travel... So there was a study done. If it's air travel domestically, you may not need to avoid as much if it's important. Now, if you can delay this to six months, it'll be better. Also judging on the creeping of the COVID infections that we're seeing, the creeping up of it and also the mask mandates off in the planes, so many people aren't wearing it. So it is a higher risk. Luckily, the planes have a high HEPA filter recycling, and they found that it was a lot better for filtering out infections in these planes. However, if you could wait past six months, it might be better just to avoid current types of infections that are going on, viral infections and such

 (40:19): [Marla O'Keefe] Thank you. What is considered immunosuppressed or immunocompromised as it relates to vaccines? I'm four years post auto transplant and take no immunosuppressants.

(40:33): [Dr. Shivan Shah] So typically after two years after a transplant and you're not on any immunosuppressants or high dose steroids, you would be considered a history of immunosuppression. Because you're a transplant patient, we would still consider you somewhat immunosuppressed because of that history. We'd always have to look out for it. However, you would be placed in another category when it comes to infections. In my mind, I would not be concerned about you obtaining any fungal infections or things like that. It's a good question. It's always again everyone's individual. So if somehow you were put on high dose steroids, you would be considered immunosuppressed. But if you're not on steroids or anything, you're more functioning like an immunocompetent person than you are as an immunosuppressed person.

(41:21): [Marla O'Keefe] The MMR vaccine is generally not given till two years after transplant, but I see several papers showing no problems at one year. What is your opinion and experience? I want to go overseas.

(41:36): [Dr. Shivan Shah] Yeah, yeah. Briefly, I think I touched on this in the presentation. During times of pandemics or epidemics of measles, there has been an okay to give it after one year, and there are papers showing that it's okay to do that. This is definitely a risk-benefit talk to have with your transplant team and an infectious disease doctor. Personally, I would be okay after one year to give it, especially if you're going to an area that may have an outbreak going on, if it's absolutely necessary to go to. Again, we would always say, "Try to avoid it. Measles is very contagious, but if you have to go then it's okay."

(42:16): [Marla O'Keefe] Thank you. I am on hydrocortisone for adrenal replacement as a result of metastasis. Would this make me immunosuppressed? I am two and a half years post auto transplant

(42:34): [Dr. Shivan Shah] Good question. So hydrocortisone interestingly enough is a steroid that is not considered a corticosteroid. It's a mineral corticosteroid. It doesn't have the same properties to cause severe immunosuppression. However, because of metastasis and things like that, you need medication to bring it up, your body may not produce steroids efficiently. We would still put you under the immunosuppressed category while you're taking that. But again, you wouldn't be at risk of certain infections compared to other people. So you would still be a little more immunosuppressed than I would hope and I'd still look out for things and I would watch out. But again, hydrocortisone is not as immunosuppressive as other like prednisone and things like that.

(43:26): [Marla O'Keefe] Thank you. Is there ever a time when my immune system will go back to where it was before the transplant, which I had an auto, taking into consideration that I have followed all the instructions from my transplant doctor?

(43:43): [Dr. Shivan Shah] Yeah. Again, it's individualized. Yes, there could be, but again, you're always at risk that this... This is just with the genetics and things like that. We're hoping after an auto transplant, things improve and you're completely different genetics at that point. It got rid of the cancer, but again, once you have cancer, there's always a risk of getting it again. So you could again unfortunately relapse, which we don't hope for, but that's always why you got to look for it. Now, if you're not any immunosuppressives, like I said before, no immunosuppressives, no steroids, nothing like that, you're closer to your immunocompetency than you were during transplant. You're much, much closer. I'd say even like 99... Not 99, but 95% close enough. So there's always a risk. You'll probably have a little more risk compared to someone without any history of stem cell, but you're close enough that it'd be okay.

(44:46): [Marla O'Keefe] You have a couple food related questions. I think you answered some in the beginning. I'll combine these. How soon after the transplant, can I go back to eating salads or soft cheeses? And what about fresh fruit that I wash myself?

(45:03): [Dr. Shivan Shah] So salads... Well, soft cheeses always be careful with. Again, soft cheeses, in general, one of the big things is listeria. In general, it's a risk. If you're on GVHD medications and such, it's very hard for you to go back to that. But if you're not on any GVHD medications, if it's an auto after two years, perfectly fine probably to go back to all that. Salads, after, I'd say, usually a year, I would give it. It's just one of those things that you have to be a little careful about.

(45:42): And then, fresh fruit washing yourself, always good. Typically, it's tricky sometimes. I don't want to refrain people from eating fruit, but again, I usually give it like six months to a year. Things that you wash yourself or you grow yourself, make sure... It's fine. Again, there's outbreaks all the time in these things. If you go to the CDC, you can find local outbreaks going on. So there was E. coli outbreak in salad packages the other month. So we were seeing that happen. Unfortunately, it's hard to navigate through it. Typically, you want to avoid it within the first year, but then after that, it's a little easier to do.

(46:28): [Marla O'Keefe] Thank you. I am 50 years old and eight years post-transplant. I had the pneumovax 24 back in my first year, but not since. Do I need to get anymore as I get older?

(46:52): [Dr. Shivan Shah] Yeah, you will need to get it again. There are actually newer guidelines out. Your primary care physician will be able to determine the time you get it. Usually, we give it after the age of 60 to 65. It all depends on what we see also immunosuppressant wise. So I would definitely go back and discuss with them. You will need it again though.

(47:18): [Marla O'Keefe] Thank you. What do you do when a patient who should be on antibiotics for life ends up with C diff from being on antibiotics? Is the C diff more dire?

(47:31): [Dr. Shivan Shah ] (Great question. Yes. And I didn't really touch on this, but all types of antibiotics will have the risk of catching C diff, which is an infection that you get from taking antibiotics. It's spores in your gut and when you suppress your gut from antibiotics, these spores come out and cause havoc and diarrhea. So C diff, basically, it depends on how bad of a C diff infection you have. I've placed patients on prophylactic C diff medication, especially if they need suppressive antibiotics for other things. So patients who have joint infections and they needed suppressive antibiotics, we've given prophylactic PO vancomycin to prevent C diff from coming back for life.

(48:16): Other things that you can eventually lead into are fecal transplants, which are... You take healthy fecal matter from a patient and you transplant it into someone's gut, meaning you do a colonoscopy, a sigmoidoscopy, and you give them good feces, but that is ways we've helped treat these patients. But typically, because most of these patients are in acute phase and they're going to be on immunosuppressives or antibiotics for life, I'll give them prophylactic PO vancomycin after they're treated for their C diff and eventually try to follow up with them for maybe a fecal transplant in the future.

(48:57): [Marla O'Keefe] I am one year post-transplant. I am not on immunosuppression. I do have mild GVHD in the liver, skin, mouth, joints, and eyes. As I consider visiting friends with kids, if I mask, is staying over their house for a weekend, considered high risk behavior?

(49:19): [Dr. Shivan Shah] Now it's one year post and you have mild GVHD, high risk, yes, if you're very close with the children, I'd say. And again, viruses could spread very easily throughout children and the family members there, so it could be considered somewhat high risk. If you're able to wear an N95... So the surgical masks are better for preventing spreading, but it won't prevent you from inhaling it. The N95 masks are better for filtering it out, so if you're able to do that, maintain some social distancing, it's okay. But again, it is still a little risky, especially with school in session and things like that. It also depends on the age of the child, of course.

(50:14): [Marla O'Keefe] Thank you. My platelet count always reads between 140 and 143. How can I get it to go higher? Let's say, 155 or higher. I am 51 months post-transplant.

(50:28): [Dr. Shivan Shah] Okay. So the platelet count, I'd say the platelet count unfortunately deals more with the hematology team rather than the infectious team, so unfortunately I won't be able to properly answer this question, but it's something... Platelets usually take the longest time to come back from my experience in this, and this is something that I would definitely discuss with your oncology team and your transplant team regarding this. They might need to see if there're other reasons for that, but typically platelets are usually the last thing to come back after a transplant.

(51:09): [Marla O'Keefe] Thank you. At what month can a transplant patient do yard work and what sort of infection can I get from the plants and the soil?

(51:17): [Dr. Shivan Shah] Great question. So typically, I would wait after one year, 100%. If you're doing yard work, gloves and a mask are highly important, even after that one year. Typical infections you could get from yards are... There are fungal infections that we look for, fusarium, aspergillus, things like that. They're mold infections. You'll initially be on mold prophylaxis after your transplant usually, if you're especially an allo. They give it to you at least for six months, if not one year, depending on how immunosuppress you're going to be. But there are so many more other infections you can also get from it that it may be hard to prevent it, especially within that one year mark.

(52:06): After one year, it's okay to go back to it. But again, if you're on steroids or GVHD medications, you may need to discuss with your primary care physician or your transplant physician regarding the risk and benefits, also the infectious disease doctor. But usually you wear mask, gloves. The last thing you want is to get an infection as a mold infection. I tell my patients usually after one year is okay.

(52:37): [Marla O'Keefe] Thank you. All right. This is a multi-part question. I'll try to do it in pieces here. If you have an allo transplant, is it true that all your childhood immunities get wiped out?

2:51): [Dr. Shivan Shah] (Yes, it's pretty much when you have an allo... It's a donor cell, so yes, you essentially... They give you a medication beforehand to wipe out your immune system essentially and then you get the donor cells. And that's why you need to be re-vaccinated.

(53:08): [Marla O'Keefe] Okay. And then, she asked, but why doesn't CMV or EBV get wiped out? And is there any benefit of having your titers checked?

(53:21): [Dr. Shivan Shah] Okay. Yeah. Great. So CMV and EBV, so those are viruses that live inside body. The moment we wipe out whatever suppression you had of those viruses, because of your own immunity, the viruses can come out and cause destruction. So that's why you're put on prophylactic medication. EBV unfortunately does not have any prophylactic medication. So for an infectious disease doctor, there's no real treatment we can give. It's just something we have to monitor. But CMV, we have prophylactic medication to give them. They will usually give it to you if you have it. So when you wipe out your system, you're unfortunately causing the CMV to come out, that's why we give you an antiviral prophylaxis. CMV, HSV are the same way. Chickenpox and EBV is the same way as well. So when you get chicken pox and it turns in shingles, it always lives in your body. You can never get rid of it and you have to just suppress it. So that's why you have to make sure you take those prophylactic medications. And what was the second part of the question?

(54:25): Titers. Instead of titers actually, what you want to do is check a PCR level, it's called CMV PCR or HSV PCR, in case you do have an outbreak of herpes. But CMV, they'll check you every two weeks or week for it to make sure that you're not getting a CMV infection in the blood. Typically, anybody that comes in for a fever and is post-transplant, I will check them, especially if they have a history of CMV, I'll check their CMV PCR, because you can always break through your prophylactic medication too, or if you're not on prophylaxis, it may come out and it may have a new infection with it.

(55:04): [Marla O'Keefe] Okay. Thank you. Where are some of these infections coming from that are not food related, for example, vaginal candida, bladder, or kidney infections?

5:19): [Dr. Shivan Shah] So yeah. Good question. So Candida is actually in your body. Everyone has it. Everyone will always have it. Candida is actually normally found in the vaginal canal or already, but, however, when you take antibiotics, you're on prophylactic antibiotics, you suppress the bacteria, they're keeping the fungus at bay and then you end up... The Candida decides, "Okay, there's enough room for me to grow, so it'll start growing out."

(55:48): Bladder and kidney infections, basically it depends. Being female and older, you can always develop bladder infections because of just unfortunately drier skin down there and things like that. A lot of times it can come from post-coital, so after having sex, people can develop it. But it's just one of the things, unfortunately, that will continue happen. And it comes from other parts of the body a lot of times too. So your body has bacteria and fungus in it, and eventually, it can sneak into bad spots, if not controlled and such. And especially when you're immunosuppressed, it does that more often.

(56:30): [Marla O'Keefe] Closing. All right. Thank you, Dr. Shah. I think that's going to have to be our last question of the day. On behalf of BMT InfoNet and our partners, I'd like to thank you, Dr. Shah, for your very helpful remarks. And thank you the audience for your excellent questions.

 

 

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