Infection Prevention and Management after Transplant

Transcription:

Moderator: Welcome to the workshop Infection Prevention and Management after Transplant.

My name is Michaela O'Brien and I will be your moderator for this workshop.

It's my pleasure to introduce our speaker, Dr. Nicolas Issa.

Dr. Issa is an assistant professor of medicine at Harvard Medical School. He's also an associate physician and an attending infectious disease specialist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute.

His research focuses on immune response to common vaccines in immunocompromised patients, and he conducts clinical trials of candidate vaccines in transplant recipients and patients with hematologic malignancies.

Please join me in welcoming Dr. Issa.

[00:58] Dr. Issa: Thank you, Michaela, for the introduction. Welcome, everyone.

What I'm hoping to do with this session is go over some risk factors for developing infection after transplant.

Also, we'll talk about the types of infection that may occur post-transplant in the short and the long term.

We'll also talk about what you can do to minimize the risk of developing infections.

We'll talk about vaccination, especially revaccination after transplant, and we'll focus more on the COVID, flu, shingles, and RSV vaccines.

[01:46] Let's talk first about the major risk factors for infection after transplant, and the foremost, the most important is the neutrophil counts. Neutrophils are the subset of the white count that are really important in preventing bacterial and fungal infections. We usually say someone has neutropenia if the neutrophil count is below 500 because that puts them at risk for severe infection.

[02:17] Also, it's also a function of the duration of neutropenia. A duration of more than three weeks and a low neutrophil count is a major risk factor for infections.

The second would be any immunosuppression and immunosuppression could be received of steroids or for those who received allogeneic stem cell transplant if they're on graft-versus-host disease, prophylaxis, they're on immunosuppression to prevent graft-versus-host and therefore might be at risk for severe infection.

Also any disruption in the mucosal barrier, either by radiation or chemotherapy, because these are the first line of defense against bacteria. For example, people who have mucositis and neutropenia, they might have translocation of bacteria from the GI tract to the bloodstream and they can become septic. Any disruption in the barrier can lead to severe infection.

[03:25] Also, if you have any hardware or plastics or catheters, and this is also a breach of the skin, which is another important barrier and might lead to infection.

Others would be something like hypogammaglobulinemia or low immunoglobulin level. These are important to prevent infection, and therefore, if they're low, then the risk of infection goes higher.

Also, if you're a recipient of cells from a donor who is not fully matched, this would require more immunosuppression to prevent GVHD and therefore put you at risk for severe infection.

Any of these factors can lead to severe infection and it's really important to know because e any modification in lifestyle or risks are dependent on those factors. As long as someone has one of those factors, they're considered a high risk for infection.

[04:33] What are the important periods after transplant for severe infection? The good news is the relative risk of infection improves or gets lower from the time of transplant.

The highest risk of infection is usually in the pre-engraftment period. This is from day zero to around day 30, day zero being the day you receive your cells. This is before engraftment, that means before the count recovery and this period, you would expect that the neutrophils, which we talked about previously are very low. So there are intense, a lot of catheters and side effects from the conditioning regimen. So this would be the highest risk for infection.

[05:30] This goes down with the engraftment that means when counts recover. However, if you're an allogeneic stem cell transplant recipient, you're still on immunosuppression to prevent GVHD. That opens up another period of risk where opportunistic infection or infection that takes advantage of weakened immune system can happen.

The post-engraftment period has the lowest risk. This is what we typically say after day 100. This is when hopefully the risk of GVHD is the minimum and not a lot of immunosuppression.

[06:14] However, it's a little bit different between autologous and allogeneic transplant. Autologous is when you receive your own cells after transplant versus allogeneic when you receive cells from donors.

Again, you can see that you have pre-engraftment, which is the highest risk, higher in allogeneic versus the autologous, But the risks go down over time.

You can see that the risk is really higher in allogeneic and the reason is because of prolonged immune dysfunction in allogeneic stem cell transplant, but also because of the immunosuppression that's needed for prevention of graft-versus-host disease.

In autologous transplant, the neutropenia is very short lived and there's no immunosuppression, therefore the risk of infection is not as high.

[07:14] What are the types of infection that we expect or can happen within these timeframes? From day zero to day 30, it's usually bacterial and fungal pathogens, also herpes virus, and this is again, because of the neutropenia. Like I mentioned before, neutrophils are really important in preventing bacterial and fungal infection. So this is pre-engraftment before the counts recover.

From day 30 to day 100, this is more opportunistic infections such as the cytomegalovirus, Pneumocystis, aspergillus and candida. These would take advantage of a weakened immune system and can happen within this timeframe. Shingles and Pneumocystis continue to be the predominant one until day 180, but after day 180, things get better relatively. So the more predominant one would be the common respiratory viral infections.

Certain encapsulated organisms, such as pneumococcus and Haemophilus, especially in those who have chronic graft-versus-host disease. And everything is dependent on if you're on immunosuppression or not, or if your immune system is totally reconstituted. So we expect more of infection for those who receive T-cell depletions or if they received post-transplant cyclophosphamide.

[08:52] What type of pathogen we usually expect after transplant? In the pre-engraftment, this is the period of neutropenia and intense immunosuppression. Usually bacterial infections are the most predominant followed by fungal. This decreases with engraftment. However, viral infections become the predominant ones in this period because of the immunosuppression that's usually used to treat or prevent GVHD.

[09:25] In the post-engraftment period, viruses remain the most predominant ones you can see less and less of bacterial and fungal infection. Hopefully this is because your immune system has recovered or reconstituted and your risk of infection becomes much lower.

One of the important signs of infection is fever. So it's really important that you let your provider know if you develop any fever, especially for those allogeneic stem cell transplant recipients who are on immunosuppressive medications for GVHD.

Any temperature above 101 should prompt a call regardless of time from transplant, because again, this is the first sign of infection and in infectious disease, treating an infection early and with the most appropriate treatment improves outcome. We really need to know if you have a fever or not.

Also, if you are a mismatch, that's the highest risk for infection and therefore any fever should be called in to initiate a workup for that.

[10:48] What are the strategies to prevent infection after transplant? We have several that we can use. First, the most important is also the pre-transplant evaluation.

 This is when we ask you about what exposures you had in the past, if you had exposure, for example, to TB, what type of occupation you do, if you have exposures to animals through occupation, if you do gardening, if you do farming, any of those will help us mitigate the risk of reactivation after transplant.

Also, we'll check for evidence of prior infection that you might have had in the past, so we can give you appropriate prophylaxis for that.

[11:35] The second would be prophylaxis. Since I mentioned we can predict what type of infection and what type of pathogen we expect during each period after transplant, we can employ or deploy prophylactic regimens to help prevent and decrease the risks.

For example, might be on acyclovir to prevent herpes simplex virus and shingles, or Bactrim to prevent Pneumocystis, or sometimes being an antifungal medication to prevent fungal infection.

It's really important to be fully adherent to the prophylaxis after transplant because that makes the physicians or the provider who's seeing you for any fever narrow down the differential diagnosis.

Most of these are highly effective. So if you're taking the medication, it's highly unlikely that you have a breakthrough with herpes simplex or shingles or Pneumocystis or CMV if you're on a prophylactic regimen.

It's really important also to be fully adherent because you don't want to get resistant to any of the medication that you're on.

[12:51] Also, there are drug-drug interaction, especially if you're on an antifungal medication, it's really important that you don't miss doses because it has effect on tacrolimus and other drugs that you might be taking for GVHD prophylaxis. So really important to be fully adhering to the prophylaxis regimen.

[13:15] We'll talk also about lifestyle modification and vaccination, which would be another strategy to prevent infections.

In lifestyle modification, we'll talk more about food safety. If you have pets, how to handle that. Also, what kind of outdoor activities and hobbies you can do about social life. When can you go back and go have a meal at a restaurant or visit people? And also, if you would like to travel, what would be the precautions?

[13:46] So let's start with food safety. Hand hygiene is really important. This is how most of the infections are transmitted. So it's really important to wash hands or carry alcohol sanitizer with you.

This would be really important because most of the infections are transmitted via contact with surfaces that are contaminated and therefore touching eyes or mouth, and this is how you end up with an infection.

Always wash fruit and vegetables. It's a really good idea to have separate cutting boards for meats and vegetables. It's really important to avoid undercooked, rare or raw meat, also raw seafood and raw eggs. Everything should be well cooked.

Also avoid unpasteurized dairy products.

No well water, probably good idea to have bottled water until your immune system has reconstituted, and also avoid certain types of foods such as soft cheeses and deli because of the risk of listeria, which could be a really severe infection after transplant.

[15:04] How about the dietary restrictions? So in general, like I mentioned, no raw seafood or shellfish and no deli for at least one year after transplant.

After three months, you may resume eating well-washed salad at home, fruits, and do takeouts. But after a year, you can go back to restaurant, but also avoid undercooked meat or no raw seafood for sure.

[15:36] Let's talk about pets. It's important to avoid getting a new pet for the first 12 months after the transplant.

Also make sure if you have pets that they're up to date on their vaccines, avoid cleaning litter boxes because there is a pathogen in there called toxoplasma that you can get from cleaning litter box and can cause severe infection.

Bird cages and the droppings of the birds, there are fungi that you can inhale and cause severe infection.

[16:09] Avoid cleaning fish tanks because of mycobacteria that can be present in the water and can cause a severe infection. Avoid exotic pets such as reptiles. There are a lot of outbreaks of Salmonella from reptiles, so no exotic pets.

If you get bitten or scratched by a pet, please seek immediate attention because your immune system might not be strong enough to fight this infection and you would need to take antibiotics or something else to prevent this from becoming a severe infection.

[16:51] How about outdoor activities? In general, limit exposure to anything that stirs up dirt or dust because there are a lot of bacteria and fungi in the soil that you can inhale and it could lead to severe pneumonias or other infections.

Also, if you like gardening or yard work, please avoid that at least until a year after transplant. If you want to garden or do yard work, please make sure you wear gloves and wear a mask so to try to minimize this risk.

[17:29] Also avoid swimming in lakes or going barefoot. If you live in area where there are ticks, please check, make sure there's no ticks attached. Areas where you have a lot of mosquitoes try to prevent mosquito bites. There are certain activities that are associated with higher risk for infections.

For example, if you work in a childcare or being a parent of children in childcare, children can have a lot of respiratory viral infection and therefore can transmit that. So it could be really severe after transplant.

[18:11] Also jobs that involve close contact with animals such as farms, pet stores, or veterinary work. These are considered higher risk and should be avoided if possible until at least a year after transplant.

Again, working with soil and gardening and mowing the lawn, all of those put you at high risk for infection.

Also, any activities that involve bird droppings, such as cleaning chicken coops or disturbing soil where birds roost or exploring caves. These are considered very high risk.

[18:57] The way to reduce the risk of infection is, again, washing hands carefully, especially if you have young kids and you're changing diapers, please make sure you sanitize with alcohol or wash your hands really well.

If you're gardening, wear gloves and masks. So to avoid stirring up soil and inhaling things that are in the soil that can cause bad infections. Also wash hands after any outdoor activities.

Again, avoid activities that have high exposure to infection. You can resume social activities after autologous transplant fairly quickly. This is mainly because autologous transplant doesn't require immunosuppression to prevent GVHD, so the risk is lower.

[19:54] But you still have to at least wear a mask when it's a crowded area, when you go to clinic or shopping, avoid also restaurants or movie theater where there's a lot of crowding within at least 12 months. Also working at school where you have exposure to kids who might have a lot of viral infection.

[20:24] You may exercise or meet people outdoors. It's safer always to be in open space versus closed spaces.

[20:34] For allogeneic transplant, this is again because of the risk of the immunosuppression. Avoid crowded areas, wear masks whenever possible, especially during the respiratory viral season and especially in closed spacess.

You may return to work or school in 12 months, and this also depends on if you're still on immunosuppression to prevent GVHD or not.

Always good idea to avoid crowded area, especially during the flu season and the respiratory viral season and outdoors would be okay.

[21:15] Now there are special considerations if you are employed and one of those occupations because of the increased risk for exposure to tuberculosis. If you're volunteering or working in the healthcare facilities or shelters for the homeless or in other settings that have high risk, they have to take precautions for that.

[21:44] Now, how about travel? So this is really important, especially if you're traveling to developing countries. Some things, please use common sense.

For example, don't go to remote areas such as the Amazon rainforest or any remote places where you don't have access to good health care. It's always good to check the CDC website.

You can type in your destination and it will give you a series of recommendations about what precautions to take, how to avoid mosquito bites, and what vaccinations you need.

[22:26] Also, taking a cruise is not really a good idea because it's confined to a place where a lot of people might have illness and outbreaks can happen, mainly norovirus and respiratory viral infections. And you don't have access to sophisticated and well-equipped healthcare, you might be stranded.

Not a good idea to take a cruise ship after transplant, at least until you're many years after transplantation. So some precautions before traveling.

Please discuss your travel plan well ahead with your transplant team.

[23:09] Sometimes you would need to visit a travel clinic to go over what vaccines you need and what other precautions you need to take to prevent infection. It's always a good idea to have a summary of your medical history and a list of medications that you're taking and make sure you're up to date on your vaccinations.

It's a really good idea to get some antibiotics such as azitromycin or ciprofloxacin for travelers diarrhea. However, any concerning signs or symptoms such as fevers or bloody diarrhea or any, you need to seek medical attention.

[23:52] How to avoid diarrhea if you're traveling? First, avoid eating raw fruits and vegetables that you did not wash or peel. Again, avoiding undercooked meat or seafood. Also no tap water or ice made from tap water. Always use bottled water.Also avoid unpasteurized milk or dairy products. Also avoid buying food from street vendors.

The safest choice would be foods that are steaming hot or fruits that you can peel yourself. Always use bottled beverages, especially carbonated ones. Hot coffee and tea are fine, and especially if you boil the water for at least one minute.

And again, please seek medical attention if you're developing severe diarrhea or if your stools have blood or you're having fevers or shaking chills, this is more than the usual traveler's diarrhea, and you need to see a medical provider for that.

[25:11] So let's talk about vaccination after transplant. These are really important.

We assume that after transplant, you lose all your previous immunity to previous vaccinations that you might have received in the past. You will be getting vaccines basically following the kids' vaccination schedule. We think that you'll be able to mount an immune response anytime between three to six months after transplant.

It's really important when it's the season for flu and COVID to get your flu shot and your COVID booster. Also, RSV vaccine is really important because we don't have any antiviral therapy for RSV.

[25:59] So any immunity that you can get against RSV is really important in preventing severe viral infections.

You will get, starting from six months, all your childhood vaccinations again, including diphtheria, tetanus, pneumococcal, Hib, hepatitis A and B. You can also receive the shingle vaccine.

[26:21] The new shingle vaccine is not a live virus vaccine and it's really important to get. We fortunately have only one remaining live virus vaccine in this post-transplant vaccination, and this is the MMR.

MMR is the only live vaccine where we have some concern if you're still on immunosuppression. And usually it's indicated 24 months after transplant.  This is when we think your immune system can handle viral live virus vaccinations.

Now, in some cases, when you have outbreaks, you can get the MMR vaccine as soon as 12 months after transplant provided no GVHD and you're not on any immunosuppression. Especially nowadays when you hear about outbreaks of MMR, you can get the MMR early, but provided you're not on immunosuppression.

[27:20] Now, just a reminder for the COVID vaccination, we assume even if you got COVID before, After transplant, you start from scratch.

We give you the series, which is usually three shots followed by a booster at six months. 

This is an important section, an important question that I typically have. One is vaccinations of household contacts.

If you have kids that need live virus vaccines or grandkids who need live virus vaccines, what precautions you need to take. The good news is your kids and grandkids can get most of the live virus vaccinations with no risk to you, except for a couple things that you need some precautions for.

[28:11] For example, the flu mist or the nasal flu vaccine is a live virus vaccine.

If your kid or grandkid gets that, you should avoid contact within for seven days, but also they can get the injectable ones, which have no risk because it's not a live virus vaccine. There's no precautions for MMR. Kids and grandkids can get the MMR vaccine. There's nothing you need to do or avoid.

Fortunately, we don't have oral polio vaccine in the United States, so they're not a risk if they get the polio vaccine because all the vaccinations for polio here in the United States are inactivated.

[28:55] Now, one caution about rotavirus vaccine. If the child gets rotavirus vaccination, you need to avoid changing diapers for two to four weeks after transplant.

[29:09] How about chickenpox? It's okay to get the chickenpox. There is about 3% chance of getting a rash after chickenpox for the child.

But there's two things you can do. One, you're probably on acyclovir, which should help prevent chickenpox, but also you can avoid contact only if they have a rash. But the good news is kids can get their vaccination.

There is no need to avoid or postpone vaccination. And it's really important for them to get their vaccinations on time.

The take home points, infections are common complications after transplant, but we have many strategies that we can deploy to avoid infection.

[30:03] The risk decreases over time after transplant and you will be able to resume good, normal, and quality of life the farther you are from transplantation.

Prevention includes prophylaxis and lifestyle modifications, and vaccinations are really an important component of the prevention strategies and can save lives. So it's really important to get your vaccinations after a transplant.

This is all I have. Thank you for your attention, and I'm happy to take questions.

Q&A

[30:41] Moderator: Thank you, Dr. Issa, for this informative presentation.

If you have a question for Dr. Issa, please use the question box on the lower left side of the screen. We'll answer as many questions as possible.

Our first question, do you recommend revaccination for post-BMT patients whose titers show full immunity six months after an allogeneic transplant?

[31:08] Dr. Issa: That's a good question.

I mean, typically we don't check titers before giving vaccination after six months after transplant because we assume that most of the previous immunity is lost with the conditioning regimen.

I'm not aware of, or at least at our centers, we don't check titers before vaccination. We just follow our protocol, which is everyone gets the vaccine that I mentioned before starting six months after transplant.

Three months for RSV, flu, and COVID, just because of the severity of these illnesses. So even at three months, you can get these vaccines. But everything else is after six months.

[32:01] Moderator: This person is asking, they've had active CMV multiple times since transplant. Fortunately, it resolves on its own.

Is there anything I can do myself to prevent future problems with CMV virus?

[32:17] Dr. Issa: So usually the highest risk for CMV is if you're previously exposed to CMV. So, I mean, we call it CMV recipient positive, and we usually now have a prophylactic medication called letermovir that you can take until day 100.

Now, the risk after that is really dependent on immune reconstitution. Usually people who continue to have problems with CMV is because their immune system has not fully recovered, either because of ongoing GVHD or immunosuppression from GVHD.

But this usually should resolve as long as these are under control and you're on lower rates of immunosuppression. So, it gets better with time after transplant.

[33:11] Moderator: Okay, we have a couple questions with regards to risk.

The first one is, I'm 210 days since my bone marrow transplant. I stopped tacrolimus on day 180, so six months stopping on tacrolimus. What's my risk of infection at that point? What caution should I continue?

[33:34] Dr. Issa: That's good news. Usually, we think if you're off tacrolimus for a month, that's usually your immune system would not have the effect of the immunosuppression anymore.

Your T cells that are usually the target of the tacrolimus should be functioning and therefore your risk of infection should be lower. So again, it all depends on immune reconstitution.

There are some markers that your provider can check, such as CD4 count and immunoglobulin level to further assess how strong is your immune system. So after those, if you're off immunosuppression, your risk should be really low.

[34:23] Moderator: Okay. This is another person who's had an allogeneic transplant.

They're five months post-allo, and they're asking about your slide on post-engraftment risk under 100 days is minimal. Does this continue to go down after 180 days? And if or when would this risk level off?

[34:46] Dr. Issa: Yes.  So, the risk continues to go down as long as there's no GVHD or you're not on any immunosuppression.

Usually we think that after a year, after transplant, if you're not on any immunosuppression, your risk probably would be very close to the normal population prevented that your immunoglobulin levels are fine and your CD4 count are fine because these are the two markers of how strong is your immune system.

But the infectious risk really continues to go down the farther away you are from transplant and provided no GVHD or no immunosuppression for GVHD.

[35:31] Moderator: Is there any way to measure post-Shingrix antibodies or is revaccination an option?

[35:40] Dr. Issa: So, the Shingrix vaccine and the immune response to Shingrix vaccine, we think it's mostly cell-mediated.

That means it's a function of your T cells, not an antibody function. Measuring antibody would not tell you if you're protected or not, because most of the lab work that we check for the shingles is antibody, but just it would show that you're previously been exposed.

It's not what we call a marker for immunity. It's more of cell immunity, meaning a function of your T cell. So as long as you're not on any immunosuppression, we think that your immune response to the shingles vaccine is adequate. But again, everyone has a little bit different rate of immune reconstitution.

Sometimes we check CD4 counts to make sure you're fully reconstituted. But again, it's not an antibody-mediated immunity. It's more of a T-cell-mediated immunity.

[36:55] Moderator: Okay, now we have a couple questions about the COVID-19 vaccination. Do you recommend the currently available COVID-19 vaccination? Or should they wait until there's a newer version approved?

[37:08] Dr. Issa: Well, I mean, you want to get what's currently available. And I know it's hard to keep up with the different strains of COVID. So, the good news is there is cross-reactivity.

Even if it's not fully matched, you will get some immunity from getting a COVID booster. I would say don't wait for a new strain or a new vaccine formulation, whatever the vaccine that's available to you.

Please go ahead and get that because we know that vaccinated people do better even if they get COVID infection. At least you avoid being in ICU or on a ventilator if you got vaccines. So really important.

[38:00] Moderator: Okay, another vaccine question regarding RSV and pneumonia.

If you're in the five to 10 years post-transplant range, how often should you be receiving the RSV and pneumonia vaccination?

[38:16] Dr. Issa: The RSV vaccination is now currently approved only for one dose. So that would be one time. That might change, but for now, it's only a one-time shot.

[38:33] Moderator: Do you have a guideline for the minimum value of CD4 lymphocyte before I receive the shingles or hepatitis B, DPT vaccines? Is there a minimum guideline?

[38:46] Dr. Issa: Usually we say anything above 200 for CD4 count is good. I'm not sure if this is checked all the time in different centers to say it's okay to get vaccination.

We typically don't check it before vaccine. We just go ahead and give the vaccinations.

But if you want to cut off, usually what we use is a 200, the cutoff.

[39:10] Moderator: Are you aware of any research showing that the COVID vaccine would cause cancer in some patients?

[39:18] Dr. Issa: I know that if you look at the Google and internet you will see association, but this is not really been validated in any data analysis.

It's just two things that can happen and it's more of coincidence rather than cause and effect.

[39:43] Moderator: Let's see, here's another question.

Can you talk a little bit about the use of antibody titers post revaccination to ascertain my immunity status?

[40:01] Dr. Issa: This depends on the centers. In a place where I practice, we don't check antibodies after vaccinations.

You can do that if you, for example, know that you have a recurrent infection, for example, with pneumococcus or other stuff to see if you're vaccinated.

But in the majority of the cases, we don't check antibodies after vaccination to measure immunity.

[40:39] Moderator: How long do you recommend acyclovir after an autologous stem cell transplant?

[40:46] Dr. Issa: That's a good question. I mean, different centers do it differently.

For example, in Europe, they stop after three months. In our practice here, we stop at 12 months. So, it depends.

But usually for autologous stem cell transplant, the risk is not that high for reactivation. We do it at 12 months because acyclovir is fairly well tolerated.

We have cases of recurrence if you stop early. That's why at least at our center, we do it for 12 months.

[41:25] Moderator: And a follow-up, is there a target dose for acyclovir?

[41:30] Dr. Issa: There are two different doses that you can use. The most common one would be 400 milligram twice a day.

In our center for allogeneic transplant, we do 400 milligram three times a day just because of the degree of the immunosuppression.  And because we don't want to break through on the lower dose acyclovir because that's a setup for resistance. But the other ones are fine.

[42:03] Moderator: This person is wondering about, they had reactions to the revaccination process. And after getting this first tranche of shots, they're developing some respiratory viruses, which led to pneumonia. And then the second and third shot sequence led to another case of pneumonia.

Three years have passed since then, and they've had some respiratory and some other issues, but no further cases of pneumonia. Do you have any thoughts on the risk of revaccination versus the risk of being unvaccinated in this particular case?

[42:44] Dr. Issa: We always recommend vaccinations. I'm not aware of any cases of getting a vaccine and you get an infection. It's really important to distinguish pneumonia.

When you say pneumonia, it could be bacterial and could be not related to the vaccine that you might have gotten. Also, there is no 100% effective vaccine.

You can get the flu vaccine and still get flu, but in that case, the flu severity is much less and your risk of getting an ICU on the ventilator is much less if you're vaccinated. So, we always recommend vaccinations.

I don't typically associate getting pneumonia or other things because of vaccines. But again, there are no 100% effective vaccines, but any vaccination is better than no vaccine.

[43:44] Moderator: Okay, there's a couple people in our audience today that are cruising fans.

One of them is six years post-transplant, and the other one is 12 years post-transplant. Is that an okay time to cruise?

[43:59] Dr. Issa: Yeah, six years and 12 years, if you're doing well, you can resume. Your immune system is as good as anyone in the general population. That's safe.

I was talking more about the immediate year or two after transplant. That's a little bit different.

But six years and 12 years, we presume that you reconstituted your immune system and your immune system as good as anyone on this cruise ship. So that should be fine.

[44:34] Moderator: Do you recommend to your patients tap water versus filtered water?

Is there a difference?

[44:42] Dr. Issa: So not really. Usually, I mean, it's not bottled water, so the still filtered versus tap is, I think, pretty much the same in terms of risk. 

Usually, it depends on the immune reconstitution and what's the risk for infection and how far you are out of transplant. These would be the most important factors. And whether it's well water tested or city water tested, that's a whole different type of risk.

If your immune system is not fully reconstituted, probably still a good idea to use bottled water rather than tap or filtered.

[45:40] Moderator: Okay, this question is with regards to the development of the CMV vaccination.

Can you tell us where it's at in development?

[45:49] Dr. Issa: Yeah, and actually, we have this study ongoing now. For now, it's too early to say it's still in phase two, which means it's a proof of concept. We had to demonstrate that you get an immune response. And I think this was presented at ID Week this year showing that you can respond to the vaccine.

It's still an early phase, so we don't have the outcome, which is does it prevent CMV or not? So, this is still ongoing for now.

[46:27] Moderator: Okay. There's a couple questions to follow up on the COVID vaccinations.

Could you repeat your recommendations around COVID vaccination?

[46:39] Dr. Issa: Yes. After stem cell transplant, even if you got COVID vaccines before, we assume that you lost all previous immunity to COVID and therefore need to be treated as you're not vaccinated. You never got any COVID vaccine before.

So, the recommendation for immunocompromised patients is three shots as the initial series. And usually we start three months after transplant. You get three shots followed by a booster at six months. This would be the full series of the COVID vaccines.

[47:19] Moderator: Okay, and what about boosters?

[47:23] Dr. Issa: Yeah, that booster then after that is every fall, same as the same time you get your flu, you will get the booster shot.

[47:34] Moderator: Do you have a guideline for the minimum value of CD4 lymphocyte before I received the shingles vaccine?

[47:42] Dr. Issa: I think I mentioned earlier, anything more than 200 is good. But we typically don't wait for, we don't measure CD4 count. But if you want a number, usually the cutoff is 200.

[48:00] Moderator: Here's another question.

Viral infections and treating those, There's some talk about the Hantavirus. Do you have any thoughts on that?

[48:12] Dr. Issa: Yeah, I mean, most of the respiratory viral illness, except for flu and COVID, we don't have an antiviral for them.

For example, RSV, parainfluenza, rhinovirus, we don't have an antiviral for those. This would rely more on symptomatic treatment and waiting for your immune system to get rid of the infection.

Except for flu and COVID, we really don't have good antivirals for respiratory viral illness. We have a cyclovir for herpes simplex and shingles. We don't have any antivirals for the Hanta virus. So, this would be only supportive care.

[49:07] Moderator: Okay, this is a question.

After an allogeneic transplant, how long will prophylactic antibiotics be taken, such as acyclovir or doxycycline?

[49:21] Dr. Issa: Yeah, so we typically continue Bactrim and acyclovir until one year after transplant. And then depending on some centers, they will check a CD4 count.

If it's more than 200, then they can stop. If it's less than 200, they can continue. And this is also provided that there's no chronic GVHD or immunosuppression.

If you're still on immunosuppression, then the prophylactic regimen would continue until you're off immunosuppression.

[49:57] Moderator: What's your experience with multiple myeloma one year post-transplant? Is there any risk, increased risk for infection from having cancer itself ongoing, or is your immunity similar to the general population one year post-transplant?

[50:12] Dr. Issa: Well, it really depends. Multiple myeloma are a little bit different because they have problems with the immunoglobulin. It really depends if they're in complete remission after stem cell transplant and they recovered their IgG level and therefore they can respond to vaccine.

If you're not hypogammaglobulinemic, you're not requiring IVIG, you have a better chance of fighting infection. But if you're still hypogammaglobulinemic, your response to the vaccine would not be as good as other non-myeloma patients.

So, it really depends on if you can mount an immune response or not, depending on IgG level and stuff.

[51:11] Moderator: What are your thoughts about getting vaccinated before CAR T-cell treatment?

[51:16] Dr. Issa: So usually, we don't do vaccination prior to CAR T because with the CAR T, you're going to get lymphodepletion. That means you're going to deplete all your immune cells.

We usually do re-vaccinate after CAR T starting from three months for flu and COVID or the other vaccines will be at six months, depending on if you are hypogammaglobulinemic or not, because that also determines if you're going to respond to the vaccination or not after CAR T.

[51:55] Moderator: Okay. My understanding is it's better, this patient's understanding, to wait for almost a year for immunization post-allo transplant.

What are your thoughts?

[52:05] Dr. Issa: We do think that the farther out you are from transplant, the better your response to the vaccine, but also you're weighing that against the risk of getting an infection if you don't get vaccination. So, it's really pros and cons.

We usually recommend vaccinations for flu, RSV, and COVID as early as three months after transplant because they're high risk for bad outcome if you're not vaccinated.

For the rest is like six months, but you're going to get a series of these vaccinations.

Although you're correct that waiting longer will get you a better response, but also the risk is what if you got a pneumococcal infection prior to you getting the vaccine, are you better off having immunity, although not full immunity is better than nothing.

From theoretical standpoint, yes, waiting longer will get you a better immune response, but you have to weigh that against what's your risk of getting an infection if you did not get vaccination.

And my recommendation would be six months after transplant, go ahead and get your vaccines. If you are three months, get your flu shot, your COVID booster, and RSV.

[53:45] Moderator: This is from a participant who joined a little bit late.

They're wondering about what your thoughts are on if they get septa after an allogeneic transplant.

What do you suggest for treatment?

[54:09] Moderator: Let's go with sepsis. We'll go with sepsis after transplant, after an allogeneic transplant.

The treatment, what would you suggest for treatment of that after?

[54:23] Dr. Issa: For sepsis, it's usually, we call it sepsis if this is a bacterial infection. And it really depends on what type of bacteria, what the bacteria are susceptible to, what were the risk factors of why you got septic after transplant.

Is it because of line infection? Is it because you have some disruption of the gastrointestinal mucosa? If there's any other risks? So, it really depends on what caused the sepsis and what type of bacteria caused the sepsis.

[54:57] Moderator: Okay, this will have to be our last question.

It is getting warmer outside and people are wanting to go outside. The question is, can people go barefoot three years post-transplant when they're outside?

[55:10] Dr. Issa: Yeah, I mean, three years post-transplant is not on immunosuppression. Again, your risk is the same as any other person not transplanted. It's really, you want to also avoid any puncture or anything, but going barefoot.

Also, if you're in a tropical area, there are other things, even if you have immune reconstitution that you'll be at risk of, such as strongyloidiasis and other stuff. So, it's usually not a good idea to be barefoot, but if you're three years out, your risk is minimal.

[55:52] Moderator: Thank you, Dr. Issa, for this informative presentation.

[55:56] Dr. Issa: Thank you.

[55:56] Moderator: On behalf of BMT InfoNet and our partners, we appreciate your attendance.

Thank you to the audience for your excellent questions and have a great day.