Jennifer Saullo, MD, PharmD 
Duke University 
Interview Date: February 26, 2020

The leading cause of death for multiple myeloma patients is infection. In this important show Infectious Disease and transplant expert Dr. Jennifer Saullo helps us better understand how to take necessary precautions to prevent infection, especially following autologous stem cell transplant. Dr. Saullo shares the types of protective medications we can take during transplant (viral, bacterial and fungal). She describes dos and don’ts of transplant for travel, crowd, masks and food. She also clarifies how to become revaccinated after transplant for maximum protection. We’re grateful to hear from her deep experience about a topic that is so practical and relevant to all myeloma patients.

 
Thanks to our episode sponsor 

 

Jenny: Welcome to today's episode of Myeloma Crowd Radio, a show that connects patients with myeloma researchers. I'm your host, Jenny Ahlstrom. We'd like to thank our episode sponsor, GlaxoSmithKline (GSK) for their support of Myeloma Crowd Radio and this program.

Now, before we get started, we'd like to share an update on the tool we created called HealthTree. We created HealthTree because it's what I wanted as a patient when I was diagnosed and we wanted to help you as a myeloma patient better navigate your disease. So you can track everything about your myeloma in a single place, like your labs or your MRD status or your myeloma genetics. You can see personally relevant treatment options. You can find clinical trials you're eligible to join. You can do all of those things even if no one else had joined HealthTree.

Now that we have over 5,000 registered myeloma patients in HealthTree, it is very exciting to be able to offer more benefits with our anonymous and aggregated myeloma stories. We've created a section called HealthTree Reports, and we have over 55 reports you can now view of the aggregated information. Of course, when it's shared, all the data shown is anonymous, but it's really interesting to see how many patients had bone fractures or the percentage of patients who have family members with myeloma or other such types of things. And we're adding new reports every week. If you've joined HealthTree already, make sure you've completed your Full Health Profile and you'll want to watch the report numbers grow when you add your answers as they are dynamic and real time.

Now on today's show, I think many of us are thinking about infections lately, especially with news of the coronavirus and while we won't talk about that too much on this show, many myeloma patients and especially those undergoing stem cell transplant can be really prone to infection due to this disease itself or to myeloma treatment. I'm very excited to have Dr. Jennifer Saullo with us today to share her research on infection prevention especially in multiple myeloma.

So Dr. Saullo, welcome to the program.

Dr. Saullo: Thanks so much for having me.

Jenny: Now, before we get started, let me introduce you just for a minute. Dr. Saullo is Assistant Professor of the Division of Infectious Diseases at Duke University. She serves on editorial boards of the Open Forum Infectious Diseases and reviews journals, including Medical Mycology, BMJ Case Reports and Clinical Infectious Diseases. She received the Meritorious Service Award at Duke and several teaching and resident awards from Columbia University. She performs both basic and applied research on topics like mass spectrometry, B cell immune deficiencies after transplant, transplant infectious disease management, and vaccination for transplant recipients.

I really think we have no one better than you to be on our show today. I'm just so excited. We're super happy to have you.

Maybe we want to get started with our questions, and the most basic question is the question that you proposed - why do I need an infectious disease doctor in the first place?

Dr. Saullo: Well, thank you for including that in the list because I get that a lot. I think when patients come in to see me, especially in speaking specifically about myeloma patients that are going through the transplant process and especially an amazing multidisciplinary team that they see, but amongst that, that means that there are many providers that they're seeing and they're always kind of asking sometimes I'm in the loop in the beginning or sometimes I'm in the loop at the end after transplant when infections result. But when they see me before transplant where they practice no infectious history, I think they're always a bit curious about why am I seeing an infectious disease doctor?

I always kind of like to explain to them that we really like to be involved both in the pre and post-transplant period. Every patient comes to transplant with their own unique risks for infections, whether it be related to their disease and their therapy or kind of their epidemiologic exposures before they get to transplant, infections that they've had, all sorts of things. We really like to be involved before transplant so that we can do everything possible to prevent infections, and then know that patients really well along the road so that if infections do happen in the post-transplant period, we're kind of there, we know them well already, and we're mindful of kind of what we think might be major issues for them as they go through that process. I think oftentimes, they feel like we get involved in this only after an infection happens, but we really like to think of ourselves as important and truly preventing infections in these patients.

Jenny: Oh, that's great. Well, you'll want to know who that person is that your facility before you get started with that process, I think.

Dr. Saullo: Absolutely.

Jenny: I know we'll be talking a lot about infection as a result of transplant or as part of transplant. But I think myeloma patients, just because one of these immunoglobulins is growing out of control and crowding out the other ways of fighting infection, myeloma patients deal with infection even before they get started with treatment.

Dr. Saullo: Absolutely, 

Jenny: So generally, can you share the likelihood of infection for the average autologous myeloma stem cell transplant patient?

Dr. Saullo: Well, it's hard to say in terms of percentage. We know that again every patient is unique, and their risk of infection at the time of transplantation is dependent upon a lot of things. One is the status of their disease, how heavily pretreated they are coming into transplant itself. Two are infections that they've had while on therapy headed into transplant. And then the third is really what their post-transplant course is going to be just in terms of their disease itself. But we know, generally speaking, there are certainly at higher risk than any average patients. They're at a little bit lower risk than our average allogeneic transplant recipient, which is, as you know, a patient that gets cells from a donor not from themselves where there's risks of things like graft versus host disease that necessitate kind of augmented immune suppression and things of this nature.

But generally speaking, we think of them as being at a quite high-risk risk for viral, bacterial, and even sometimes fungal infections and the other atypical kind of pathogens heading through transplant - more so during certain periods of transplant, which I suspect we'll get to, on the whole, infectious complications are a major component of the morbidity and even mortality that we see in autologous stem cell transplant recipients.

Jenny: And not just for transplant patients, but I think many myeloma patients die of infections. It might be even the leading cause of death for myeloma patients, not the myeloma itself, but the fact that either the myeloma has increased or grown and that's not transplant related necessarily, but it's a big issue.

Dr. Saullo: It is and, in fact, I think stepping away from the transplant realm, multiple myeloma patients, especially in those first several months after diagnosis or after a time of diagnosis, are probably at one of their highest risk periods for infection. So we're not even talking about post-treatment and coming into the kind of a consolidated phase with transplant. They absolutely have ebbs and flows of infectious risk with along the path even before transplant, most definitely.

Jenny: So you mentioned viral, bacterial, and fungal types of infections. What do you find as the most common infections that occur either prior to or following transplant?

Dr. Saullo: Thinking about the transplant itself, maybe just focusing for this moment in time on transplant, I think we generally think in terms of most common infections in a timeline type fashion just to kind of generalize that. In an autologous transplant, I think about them in a pre-engraftment phase, meaning at the time of their consolidation when they received their therapy for the transplant before they received their cells until their white count recovers, which we consider are their white count engraftment and really through that first 30 days.

And then there's a second time period that we just call the post-engraftment phase. The risks and the different types of infections really vary based on that period. So around the time of the transplant itself when patients are most heavily immune-suppressed in the sense that they are neutropenic, there's breakdown of mucosal barriers, either from mucositis related to the chemotherapy that they're receiving or the presence of central lines, essentially every patient coming to transplant will have a central line in place, and they don't have those key innate immune cells, the neutrophils, to combat infection. It's at that point that they're at most risk for bacterial infections. So certainly Gram-positive staph aureus, strep viridans coagulase-negative staph. They're also at risk for Gram-negative pathogens and coliform bacteria. Think about E coli and Klebsiella, but also kind of more formidable pathogens like Pseudomonas.

During that time period, they're also at risk for some types of fungal infections, a little different than allogeneic transplant patients, but we do worry about candida, which is the type of yeast that lives in the intestines as part of our normal flora. But when the flora gets disrupted and patients are neutropenic, it can be very severe. It can cause severe infections in these patients. And then in that early period, in terms of viral infections, the one we worry about most is probably herpes simplex virus, which we oftentimes think about oral or genital herpes, which is probably the most common manifestation, but it can be much more severe than that with disseminated disease involving organs, the brain, the lungs, the liver.

So those are probably the biggest and most common pathogens that we worry about during that period. And then community risk for viral infections, influenza, they have no time period. They're always lingering. There's always that risk. And then in the post-engraftment period, we begin to worry about things that are more related to delayed immune reconstitution both of the humoral and also your cell-mediated immunity. So we worry about more atypical stuff. Sometimes CMV (cytomegalovirus) occurs. It is common in autologous but we do see it in autologous stem cell transplant patients. Zoster or shingles is a biggie that we worry about during that period. And then things like pneumocystis jirovecii zero is a type of atypical, essentially fungal pathogen or type of pneumonia that we can see in that patient population in varying degrees of risk, kind of depends upon the patient and what their pre and post-transplant myeloma therapy will consist of.

Jenny: Okay, wow. It makes me nervous just hearing about all those.

Dr. Saullo: Just to say, around all of those, we have wonderful prophylactic therapy.

Jenny: We're going to talk about that!

Dr. Saullo: Yes, let's go to that.

Jenny: So those are the most common things. During that 30-day window when patients have to be super careful and their neutrophils are at an all-time low and they're re-growing and everything, that's interesting to hear about this. Let's talk about what you do to prevent those in both of those stages. I like how you've broken it out into two stages.

Dr. Saullo: And just to clarify and to make you feel less nervous, in an autologous transplant recipient as opposed to an allogeneic, the white cell count recovery is quicker. So really, the engraftment is anywhere from eight to 14 or 15 days after the stem cells are reinfused. Whereas in allogeneic transplant, depending upon the source, it may be much, much longer. It may be 20, it may be 30 days after that. So there is a clear difference there. Hence, the risk is lower for infections.

So around the time of the transplant, again, I'll tell you our practice pattern. Certainly, every patient knows this. The center you go to and the people that manage you may do it a little bit differently. The guidelines of the data that is there is certainly open for interpretation at our own institution for prevention in that early period, that first 30 days. We typically have patients on an antiviral therapy and that's either acyclovir or valacyclovir to help prevent that herpes virus and does an excellent job in doing that. We give that orally. We can give that intravenously. We can modify that as needed.

In our myeloma population, we do provide bacterial prophylaxis in the form of levofloxacin, which is a fluoroquinolone antibiotic which has broad spectrum coverage for Gram-positive as well as Gram-negative organisms. Now, not all centers do that. These patients are intermediate risk, and some choose to do that during the period while the white cell counts are down and other centers don't. There's lots of reasons to do it or not to do it. The reasons that people may refrain are things like affecting your microbial flora, the risk for C. difficile infection, which is also ever present during this period, and other side effects from these medications as well as the emergence of resistance. But in our center, we do that when patients are neutropenic and through engraftment.

We also apply fungal prophylaxis for the medication called Tucanozol to prevent the candidal type infections. Again, the fungal and the bacterial we only do during that highest rest period when those patients' white counts have not yet recovered. And once they recover, we take that away.

Jenny: Okay, that's great. I had sent you a question before about levofloxacin. I have read some studies that it actually could help delay progression-free survival in some patients, and I don't know if that's just because it’s infection related or if it has some other impact. Do you want to just share the data that you've heard around that use and I guess the rationale behind why you're using it?

Dr. Saullo: Yes. I think there are two different time periods. So there is data that I think is currently being discussed quite a bit, certainly among individuals and our center and across the world and in terms of the myeloma population. One of them is not related to specifically transplant but patients at the time of initial diagnosis. There was data that was presented at ASH in 2017 and was just recently published, actually. I think it was just in 2019, in Lancet Oncology. It was called the TEAM study. It looked at levofloxacin prophylaxis and this very patient population, initially diagnosed myeloma patients. And during that first 12 weeks of therapy, with the rationale kind of as you alluded to at the beginning of the show that these patients, when they come into care and are diagnosed, they are profoundly immune suppressed because they have a disease that causes multimodal immunodeficiency, and hence are at very high risk at the time of diagnosis for infections. And then you throw therapy into the mix, which in and of itself is immunosuppressive.

That study, it was a randomized controlled trial where they administered levofloxacin to patients during that initial 12-week period, and they found that there was a reduced incidence in both febrile neutropenia as well as in death. This is one of the first studies to show, the survival benefits. It has not been shown in other studies in this population during this time period.

This study has generated obviously a lot of discussion and changes, frankly, in the way people are practicing in terms of their application to the early myeloma therapy group. I think kind of stepping back as a patient and wondering why in the world would my provider not do this? I'm not going to have febrile or I'm going to have reduced febrile neutropenia. There'll be a reduction potentially in mortality here. Why would we not do that? But it's to realize that every center has its own epidemiology, and each hospital has their own what we call antibiogram. So we know that a certain percentage of the most common Gram-positive or Gram-negative bacteria at our institution are resistant to Levaquin or maybe sensitive to Levaquin. And if it's above a certain rate, that drug may not actually have that benefit in you so that you have to think about the individual institution in the community surrounding that. Will that drug truly be effective for that patient?

And there are issues with giving patients just broad spectrum antibiotics for extended periods of time, alteration in their microbiome, their flora, their bacterial flora and their antibiotic-associated diarrhea. The fluoroquinolones, the Levaquin that was used in this study can be associated with tendon toxicities. There are all sorts of things and the questions and concerns for emergence of resistance, the emergence of C. difficile infections. So all of those things come into play when people make a decision, but that is data that's out there that's important for the Myeloma Crowd to know about. I think it's changing the way some people are practicing.

Around the time of transplant itself, there is data surrounding that. There are NCCN guidelines that we follow. Levofloxacin is considered in these patients for all the reasons we discussed, because we know that they're neutropenic and they're at high risk for invasive bacterial infections during that period. And that is the reason that we typically would apply it in that situation.

Jenny: And I remember seeing research that it extended progression-free survival, I think, even after transplant. So it was very transplant related, but that's so interesting. I didn't know about the newly diagnosed myeloma as well.

Dr. Saullo: Yes, that data was presented in 2017 but it just recently got published not too many months ago. It is definitely a good and very important read.

Jenny: Well, during that pre-engraftment to engraftment stage, that 30-day window, what specifically can patients do besides taking the antivirals and the antibacterials and the antifungals that you talked about to help prevent infection? Because that's a really sensitive window of time, I think.

Dr. Saullo: It is. I think that's probably the most sensitive window in the transplant realm. There's obviously other periods where we want them to be very careful and timeline set for them, but that is so important. And it's so hard I think because at some point in that 30 days, you're definitely going to start feeling better and wanting to do more and more and just needing to be careful in terms of what we do. So we really talk with the patients a lot about the importance of having a single or one or two caregivers, ensuring that they optimize their nutrition. We give them very specific instructions on what to eat and how to prepare those meals. We really ask that during that period of time that they eat in the home and avoid going to crowded restaurants and certainly avoiding things like buffets or things where there are certain risks for foodborne pathogens and infections.

We also really ask that they minimize their exposure to crowded areas. Really, most of their life in that 30 days is really coming to clinic and going home and really trying to minimize the time that they're spending in crowded places - not going to Walmart in the middle of the day and not going to a busy gym and things like this. So just being mindful of their surroundings and trying to avoid crowded places. And focusing on optimizing nutrition, exercising as feasible, getting good sleep, and just focusing on getting better and getting to the transplant and being compliant with medications, being compliant with this type of thing.

Jenny: Right. Do you give patients a specific diet to eat? I know that it's just kind of helpful to be given the recipes or just ideas, because you can still eat really healthy during that transplant process and get good nutrition, but you might have to cook things.

Dr. Saullo: Yes. In every center they give a little bit different instruction on diet and this kind of things. But certainly, there are things, I think, that the most important thing is telling patients what to avoid. Obviously, you want to give them all the great things that they can eat but making sure that you're very clear on what they should not eat. Part of that is, as I discussed, going out and eating the foods that are not prepared by them and buffets and things like that. You just absolutely don't want them doing that. Unpasteurized milk, cheeses, things of this nature, we want them to avoid. Making sure that their meats, their eggs, all of these raw foods are fully cooked and with fruits and vegetables, making sure that these are cleaned, well cleaned, that any sort of bruised fruit or vegetable (if there’s a bruise or break in the skin) is not eaten. And making sure that all of these things are washed.

We talk about other things, certain vegetables and things that they should not be like sprouts and things like this, herbs that they are getting from various and sundry places that we want them to stay away from. We often talk about water and the water supply. Usually, they're closer to the transplant center, and they're using the municipal water supply. But certainly, there are situations where they're in an area where they only have well water, then they should not to be drinking that. They're only supposed to be using bottled water. If they're going to be using well water for any reason, we go through the process of boiling the water and things like this.

We also make sure that we're very clear about other environments that they should avoid, especially in these first 30 days, like recreational activities. They should not be going to swimming pools to hot tubs and all of these things that we're making sure that they stay away from because there are very clear infectious risks related to those water sources.

Jenny: Yes, that's a great review. I'd be happy to share that on our website as well because they are handy lists.

Dr. Saullo: Yes, there's a document from the US Department of Agriculture and the FDA that we share with our patients. It's like a "food safety for transplant recipients". It just so nicely details kind of even just the preparation of food in terms of making sure the raw, the eggs and the chicken and the things and how you should prepare that, how you should separate that. It really goes into very nice detail in a way that that makes sense, that just seems logical. I think our patients really appreciate that and they refer to that often.

Jenny: Yeah, that sounds like a great resource. Amazing. Okay, do you want to also talk about the post 30-day time period or the post-engraftment time period, what you do to prevent infection?

Dr. Saullo: Sure. So in that post-transplant, in that post-30 day, as I said, the community acquired viral infections, that risk is kind of always there. We tell patients again that they should avoid crowded areas and maintain a good social distance when they're with people that they don't know well. Or if anyone certainly around them is sick, that they should even try to avoid that person or if they have to be in close proximity, again social distancing, wearing a mask. And then in terms of pharmacologic interventions, we continue them on the antiviral, the acyclovir or the valacyclovir. Only at that period, once they’ve engrafted, we really are transitioning our concerns and our focus mainly on herpes zoster or shingles, essentially, and shingles prevention because that too is a very significant pathogen in these patients. They're at high risk for that and that drug does quite a good job in preventing that.

In some patients, not all, we apply Bactrim. If a patient has a sulfa allergy, we use alternative drugs, pentamidine, etc. These are the alternatives to prevent pneumocystis, which is again the type of atypical fungal pneumonia that we can see in this patient population as well. And typically, we continue the pneumocystis anywhere from three to six months following transplant, although that risk is reassessed at that three or six-month mark and depending on what their kind of maintenance they are doing and what's happened in that early post-transplant period, we make a decision whether we'll stop that or continue that. And with antiviral therapy, that's a little bit the valacyclovir or acyclovir. That's a bit of a moving target because the introduction of the Shingrix vaccine has changed the way we think about that.

But by and large, at least at our center, we continue that for six to 12 months. The NCCN guidelines are six to 12 months. At our own center, we continue at least until 12 months. And then we reassess that risk again at that 12-month mark and it really depends upon the net state of immune suppression of that recipient and kind of what is happening in terms of ongoing therapy for their myeloma and the status of their disease.

Jenny: So the acyclovir is what you do for six to 12 months additionally or something else?

Dr. Saullo: We do acyclovir or valacyclovir for six to 12 months for the viral prophylaxis, primarily focusing on shingles, yes. We also vaccinate them, our autologous transplant recipients with myeloma. We vaccinate them with the Shingrix, with the recombinant inactivated shingles vaccine.

Jenny: Let's talk about vaccinations as a whole and really kind of go into depth, because I think it's pretty confusing for patients. Should I get revaccinated? When? How should I get revaccinated? Do I need multiple shots? So anyway, if you want to just walk us through what you typically do for patients, that would be fantastic.

Dr. Saullo: Sure. And just to say, it's not just the patients that get confused. I think the providers as well, so you're not alone. It is a complex task. I care for a solid organ transplant and hematopoietic cell transplant. Certainly, the solid organ transplant revaccination guidelines are a whole lot easier than the stem cell transplantation. So the one thing I'll say is just to put a plug in. Patients that are really interested and want to read this in detail is Paul Carpenter and Janet Englund had published in Blood one of the How I Treat series, and it's How I Vaccinate Blood and Marrow Transplant Recipients. I think it's one of the most excellent "frequently asked questions." It's in a question and answer format, and it really nicely delineates many of the questions. Sometimes the medical literature can get a little bit daunting in the context of too much detail, but I think the scope of the paper and the way that it's written that patients would enjoy reading it. It brings up a lot of the questions that the patients directly ask me about.

So the way we tackle vaccinations in our autologous stem cell transplant patients is we vaccinate essentially everyone with the idea that we know that people may have received their childhood vaccinations, but the immunity to that wanes - and it wanes substantially after an autologous transplant. We don't rely on the fact that they had childhood vaccinations as being something that will afford them protection as they go through the post-transplant period. We know that these patients are at very high risk for many of the pathogens that these vaccines are set up to prevent. So we really feel like it's important to vaccinate these patients. So we kind of forget that they ever have those, and we start anew.

We typically don't start vaccinating patients until the least six months mark in the post-transplant period. The exceptions to that are two-fold. One is the Shingrix thing. That is the inactivated recombinant single vaccine. The only one that is FDA approved is the GSK vaccine (brand name for that as Shingrix). And we start that in our autologous stem cell transplants for any patient that is 18 years or older. Typically, it's a good 50-70 days post-autologous stem cell transplant (never sooner than 50 days). And then we repeat that with the second vaccine one to two months later. And the other vaccine that we sometimes do before six months is the influenza vaccine. We do an annual influenza vaccine. We like to ideally do it at the six-month mark, but if the six-month mark doesn't fall right, meaning there is lots of flu happening in the community before that, we will vaccinate them earlier and then we have schemata setup where we'll revaccinate them. Sometimes we'll do a double vaccination to optimize their immunity in that setting.

And then at the six-month mark, we reassess and see where the patient is at. At that time, we may or may not start vaccines, it really depends on their net state of immune suppression, what sorts of therapies they're receiving. And for most autologous transplant patients, we can start vaccinating them at that point. If we don't, we typically push that then to 12 months and start everything then. But at the six-month mark, if we do proceed, we typically do the protein conjugated vaccine, so that stuff like your pneumococcal, which prevents streptococcus pneumoniae, and we do the Haemophilus influenza B vaccinations and the meningococcal vaccinations. And then starting at the 12th month mark, we do many of the other vaccinations, so the tetanus inactivated polio vaccine, hepatitis B, hepatitis A. We begin to think also in cases where it may be relevant in terms of human papillomavirus, so we'll do the vaccination for that as well.

So that's the general schemata. All of the vaccines I have just mentioned to you now are all the dead or inactivated vaccines. The other group of vaccines will be live attenuated. And obviously, we don't want to give those to transplant patients while they're still immune suppressed with that theoretical risk that you could actually give them the infection that you're trying to prevent. We typically apply a rule that they have to be two years out from transplant, and a year off of immunosuppressant therapy and not actively receiving a type of supplement called immune globulin, intravenous immunoglobulin (IVIG).

With measles, mumps, rubella, which is probably the primary live attenuated vaccine that we talk about, we have kind of lightened up that criteria in some patients because, obviously, that we're having issues with the non-vaccinators in the world in the United States and our loss of herd immunity. We are trying to protect these patients maybe sooner than that two-year mark. And so there are certain criteria that if people meet those criteria and many of our autologous stem cell transplant patients do, we may vaccinate them before that two-year mark if there's a perceived increase risk either based on their travel or where they're living geographically within the United States.

Jenny: Is there a way to test if a patient has vaccinations still active in their body? I think there's a test. I just don't know the name of it.

Dr. Saullo: Yes, there absolutely is. For example, hepatitis B, we check a hep B surface antibody, which is an indicator of immunity. So if it's above 10, that's considered a positive titer. We can do this for hepatitis A. We can do this for tetanus. We can do it for many of them, measles and mumps. The reason we don't just do before we vaccinate is that we don't feel there's any utility in doing that because even if they have some level, at least serologically of immunity, we don't rely on that. We know that we need to fuse that immunity. So let's just say, you tested someone for hepatitis B immunity and they had it, I don't really care. I'm still going to want to vaccinate them with the hepatitis B vaccine.

What I think is more important is actually after you provide those vaccines following transplantation, that then you reassess to see if they've had a response to the vaccine. Are they truly able to mount an immunologic response to the vaccine? So that you can feel more confident that these vaccines are working. We know that these vaccines are not as immunogenic. They're not as effective in this population as a normal immune competent host, but we do think there is clear benefit and over time that benefit increases in terms of their immune reconstitution following transplantation. So we're just trying to build up that immunity as they go.

Jenny: It's so interesting, because I know that's the case with the flu vaccine that sometimes you'll give the flu vaccine, but in this patient population, you really need to give a second dose or a third dose and then a follow-up dose. So that's interesting. And "titer testing" is the phrase I was thinking of. That's so interesting that you just go ahead and do that regardless. That's really fascinating.

Dr. Saullo: Yes we do. The point you mentioned about the flu is an excellent point because I get this question all the time. Is just me getting the standard quadrivalent or trivalent flu vaccine enough? My stance on that is it is so much more important that patients are vaccinated than not. The most important thing to me is that I get the flu vaccine, whether it's the trivalent, which has the three different strains or the quadrivalent or the double dose or doing a booster dose. I just want them to get the vaccine because we have data now to support that just getting a simple trivalent influenza vaccine reduces overall incidence of influenza in these patients, their hospitalization and related morbidity with influenza. So just getting vaccinated is important. And also making sure that their family members are vaccinated, the herd immunity of the crowd that they are with, getting them vaccinated is so important.

But then there are some data and it's really interesting data and a lot is being published. There are really smart people doing a lot of great work looking at this. Is there a benefit of giving these patients the high dose? There's a high dose trivalent vaccine that's been FDA approved for patients that are over 65, that instead of having just 15 micrograms of this hemagglutinin, it has four times that amount. And is there some benefit to giving it to the patients that we know already are going to have a reduced immunologic response? Can we boost that immunity and thereby do a better job at preventing the influenza? And there are groups within the solid organ transplant community as well as in the hematopoietic cell transplant that have shown benefit? If it is more immunologically robust, the other concern is, are there more untoward effects by giving patients the higher dose?

So there is data that has emerged to suggest that. The efficacy data is lacking, but there's definitely safety and immunogenicity data that is there. I think more centers are moving towards using the high dose. Or what we sometimes do in patients when it's before the six-month mark and they get transplanted, and at the four-month mark, they're right smack-dabbed in December, and there's lots of flu happening. We'll give them a standard dose vaccine and then four to six weeks later, we'll give them a second as a booster to optimize that immunologic response. But again, I think the most important thing is just getting them vaccinated.

Jenny: That's so interesting. Well, I actually need to have a conversation with my doctor now. When you talk about the pneumococcal vaccine, I guess there are different valences -- can you explain what that means and the differences between these two. And do you have a preference or a suggestion on the pneumococcal vaccine?

Dr. Saullo: Yes. That's a great question. So there are two pneumococcal vaccinations that we do, and we do both. We recommend both in our patient population. There's the 23-valent which is a polysaccharide-based vaccine, and there's the 13-valent which is a protein conjugate vaccine. When we say valent, it's covering 23 different types of pneumococcal infections, whereas the 13-valent is more narrow spectrum, so it doesn't cover as many types, but it covers some of the most common that are associated with invasive pneumococcal disease.

But when we revaccinate patients, what we know is early on post-transplant when we start this in the three or we typically do six-month mark that we start this vaccine, they're much more likely to elicit a better immunologic response to the protein conjugated which is the T cell dependent vaccine. So we give them the Prevnar 13 - the narrower focused vaccine first. We do that as a series of three, and we separate those doses by at least a month. So they get three of these doses. And then after they've had all three of those, they are further on post-transplant and maybe six to 12 months later, we will give them the 23-valent as giving him the whole gamut to boost the types that are included in both of the vaccines, but also to add in these additional types that were not covered by the 13-valent. We hope that at that later points in transplant, they'll respond better to that polysaccharide-based vaccination.

Jenny: Let's say you're quite far out from transplant, you're not within these six or 12-month windows, would you just get the Prevnar in addition or just do the 23-valent if you haven't been revaccinated?

Dr. Saullo: I probably would still do that same series. I was still just start there and give you all four, give you the three and then and one. The important thing is that if you've gotten the 23-valent already, and sometimes people, if they haven't gotten the 13th, someone somehow has slipped in a 23-valent because in normal adults, when we're doing boosters, in certain populations, when we do a booster, it's the 23-valent that we do. If a patient somehow didn't get their 13-valent (the three doses) but did get a 23-valent, we usually then request that you wait a year before you give the 13. There are some nuances in terms of the timing of it. But I probably, if they hadn't had any of them, I would still administer the full series to give them the very best chance of kind of immunologic response.

Jenny: Right. And then once you're done with that series, you do it annually again or that's it?

Dr. Saullo: No. At some centers, they assess the response, the pre and post-response the pneumococcal vaccine to see if the patient demonstrated response to the vaccine. Although there are not really clear accepted criteria in that population, many centers do do that and have their own criteria by which they do that. But there's the question of when to revaccinate. So we typically will just do the three of the 13-valent and then the 23-valent. And then when patients turn 65, they usually get a booster of the 23-valent. But before that time, some centers will every five years just do the 23-valent where some don't.

I think it really depends upon your patient and kind of what their next set of immunosuppression is at that five-year mark after you've done that or after you've completed this series, whether you might consider doing another booster. You would never repeat that whole 13-valent.

Jenny: Okay, great. A question, kind of jumping back to what you were talking about before in terms of wearing masks, staying out of crowds, for stem cell transplant patients, how long does that stage really last? Like for how long do you really need to do that or be careful on planes or things like that?

Dr. Saullo: Well, again, it really depends a little bit on the patient, I think, and what their post-transplant course is like because some patients certainly are more immunosuppressed following transplant than others. But in general, certainly, we ask that patients in that first 30 days and actually I'd say in the first three months, we really ask that they try to avoid crowded spaces and really limit the number of people that they are visiting with and making sure that being very cognizant of the individuals around them, that people coming to visit them are feeling well. After that first three-month period, we lessen the restrictions.

At the six-month mark, we start talking about if they want to travel, although we prefer to push off any sort of international travel until they're at least a year out from transplant so that we can get the process of immunizations and all these things started. In terms of international travel, it depends on where they're wanting to go if we really want them to do that. But I'd say the closest restrictions are in that first three months.

Jenny: For those who can travel internationally like you're saying (none for a year, hopefully), are there any other additional vaccinations that people should consider like measles or yellow fever? I know the coronavirus is a crazy thing right now, but you can't really vaccinate for that.

Dr. Saullo: No, you can't. I'm glad you bring this up because I think that first and foremost thing I would say to any transplant patient before you consider international travel, you want to go to either a travel clinic or to see one of your transplant infectious diseases providers that is comfortable with the management of travel-related vaccination and guidance and advice and can give you kind of a solid plan about where you want to go or what you need to do depending on where you want to go. I think the risks and the additional vaccines that you need depend upon the time of year you're traveling, where you're traveling to.

Certainly right now with coronavirus, for example, I've had a couple patients that have approached me about cruises to Asia or that area. We are strongly advising patients not to do that. There are certain restrictions now and the CDC web pages updated daily on the restrictions, certainly traveled to mainland China. And there are several new sites now, South Korea and other places, where the travel has become restricted. I'd refer the patients and people to the CDC website for those almost daily updates in terms of the travel alerts.

But kind of stepping away from coronavirus, there are definitely other vaccines outside of our standard vaccines that we think about depending on where patients are traveling. So yellow fever is one that you mentioned. That is a mosquito-borne viral hemorrhagic fever that have associated morbidity and mortality, typically associated with South America and other tropical and subtropical areas. And it is something that we like to obviously do everything we can to prevent patients from becoming victims at home - mosquito repellent and mosquito avoidance and all the things that they need to do is do that - but in addition to that, we can vaccinate them.

The problem with that is that that is a live attenuated vaccine. It's a live vaccine and I certainly am not feeling comfortable giving them a vaccine with the potential for ill consequences for someone whose immune system is not fully intact. Depending on what they're wanting to do and why they're going there, I might even advise against it because it's a vaccine that we can't give to them at that time and maybe think about going somewhere else where that risk is not so high - or where the activities (if you're going running through the Amazon) is not as is high.

And then there are other things like typhoid fever. There are some vaccinations that we can give for patients going to areas where typhoid is erndemic, or salmonella, something that is an oral foodborne pathogen that can make patients quite sick. The preventative measures include an oral live type of vaccine and then an inactivated vaccine. And so we always want to make sure that if patients are going to be traveling to those areas, we vaccinate them with the appropriate vaccine, whether that be a live attenuated or inactivated or a dead vaccine. And then also we spend a lot of time talking about what you eat, what you don't eat, where you go, what you don't do, all of these things in terms of important travel advice for places that they're going.

But there's other things when people travel internationally. There may be things with their job or what they're doing in terms of rabies, malaria, meningococcal disease. I mean, there's all sorts of important things to discuss with them depending upon their choice of travel. All of these things are things that we have to think about. But again, it depends upon the place that they're going to and the time of year. It's why it's so important that they think about seeing a travel specialist, at the very least a month in advance, although we prefer that they come at least three months in advance so we can really kind of get their plan put into motion before they travel.

Jenny: Right, because you might have to get some good shots to protect yourself.

Dr. Saullo: Right.

Jenny: I have a question about facemasks because you're seeing a lot of them out there nowadays. There are different kinds, as we know. What do you recommend for myeloma patients post-transplant in that really critical 30-day time period and type? They're hard to wear. They make you feel like you can't breathe very well. So not an easy thing to do, to wear those, but what do you suggest?

Dr. Saullo: I think you ask 10 people in the room, and you're going to get a different answer on this one. But I think in terms of the mask, so there's the surgical mask or the other common mask that might see as the N95, the particulate mask. And that one of the two is certainly even more uncomfortable and I think restrictive. Most of our patients don just a surgical mask. What I recommend to patients is if they're at home and with their loved ones and with their healthcare provider, certainly in their home, they do not need to be wearing a mask. When they're in crowded situations not intending to be but let's say they're at the hospital and they're getting a test done and they're in a waiting room, I do recommend that they wear it. But I don't want to give them a sense of false security. I am not saying that if you wear a surgical mask you're 100% protected against infections. By no means am I saying that. That's not been proven. But what it does do is it reminds people of social distancing, - if people are thinking about their own self-preservation and they see someone with a mask, they might step back a little bit and not get up so close to you.

So in that sense, I think it's just a gentle reminder to people to take a step back, to not get into your personal space, and in that way indirectly afford some protection. I do recommend that they do that when they are in a crowded waiting room or in a crowded situation for those reasons. But the understanding that it's not a perfect solution and that the most important thing is hand hygiene, personal hygiene and in terms of either washing the hands or using the alcohol-based washes, not putting your hands on your face or touching, you know, being very cognizant of that because I think that is probably the most important thing. And that mask is just kind of secondary but does maybe potentially offer an additional benefit. If patients are having a really hard time wearing the mask, then I don't think it's the end of the world, and I don’t tell them, listen, if it's making them uncomfortable, I don't think it's like the end all, be all in terms of them wearing that mask. And so I don't force that upon them by any means. I don’t typically recommend the N95 mask, just for those things that I mentioned. I think a surgical mask is sufficient.

Jenny: That's great to know. I know there's been a lot of discussion lately about kinds of masks. I think N95 masks might be a little hard to get right now.

Dr. Saullo: Yes. Certainly I'm talking about this in the context of not being a healthcare professional. I'm talking about patients and this outside of coronavirus because obviously in the healthcare setting right now, there are different recommendations in terms of N95 and these kind of things. So that's a separate discussion.

Jenny: Right, right. Well, gosh, our friend Paul Kleughten helped me connect with you for the support in the show, and you’ve been perfect. I've taken up so much time. We're going to do some caller questions, if you don't mind. Go ahead with your question.

Caller: Perfect. Thank you. I just have a quick question for you. Do you recommend that family members get live vaccines?

Dr. Saullo: This is a fantastic question. I'm so glad you asked this one. I love this question. Let me step back a little bit. So I think the most important thing, of the equal importance to our transplant patients getting vaccinated, is their loved ones, their family members, the people in closest proximity to them being vaccinated, whether that be for the flu or whatever age-relevant vaccines they need, and that includes live vaccines. I think there are some caveats with certain live vaccines. One is for influenza. There is a live attenuated nasal vaccine. We recommend that if the caregivers are going to get the influenza vaccine, well, one, we're recommending absolutely get it. But two, we're saying ideally to get an inactivated vaccine. There's really no reason to get the live attenuated. They should get the inactivated vaccine in that scenario. But for things like measles, mumps, rubella, primary varicella vaccine, so the chicken pox, these types of live attenuated vaccines that if they need those, they should absolutely get them. And there is nothing that says that they need to be away from the patient when they get those live vaccines.

There are a few vaccines where there are concerns for transmission from the caregiver to the patient. One is, as I mentioned, this influenza vaccine. The other is the oral polio vaccine, which is not commercially available in the United States anymore. And then the other one that we do have some concern about is rotavirus, which is a vaccine that is given to babies, to infants, for gastrointestinal diarrhea related to the virus. In that scenario, we do say that if there's a baby in the home that is receiving that vaccine, that that individual should not be changing the diaper for at least four to six weeks. Typically, we usually try to have them have someone else doing that job anyhow in the time of transplant.

But for most live attenuated vaccines, it is fine for the family member to get that and it doesn't mean that they have to be furloughed for some extended period of time. Whenever there's a question about that, we prefer that they do to ask their provider about it but certainly not postpone those vaccines just on the basis of them being live attenuated without some discussion with their provider about whether or not some sort of interaction needs to take place in terms of furloughing them. In most situations, there isn't a need to do that.

Caller: Okay, awesome. Thank you so, so much for that response. That's great.

Dr. Saullo: Thank you. It's been wonderful.

Jenny: Great, thank you so much. Great question. Caller, go ahead with your question.

Caller: Hello, yes. I'm due to have a transplant in two weeks, on the 24th of March. What about pets when you come home from hospital?

Dr. Saullo: That's also a great question. The dogs and cats, we know our transplant patients love their pets and we want you to continue to enjoy your pets and that's part of your quality of life around and after the time of transplantation. There are some certain guidelines that we give you. Each transplant center will give you their own specific guidance. In terms of dogs, we ask that you are sure that you're keeping the dogs up to date in terms of their veterinary care and their vaccinations and that they're being fed appropriate commercial-based foods, that you not sleep with the pets and that you wash your hands any time you pet, before and after, most importantly after, petting your animal and that you not let the animal lick or touch your face or come in contact with you in that way. Just obviously using good sense in terms of hygiene with that animal.

For cats, most of that is the same and then there are the issues surrounding their litter box. We really say that the transplant patient should not be changing the litter or doing anything where they'd be in contact with the litter box or the feces of the cat or the dog for that matter, but we specifically worry in the context of the cat because of this risk for pathogens in their stool, the most notable being toxoplasmosis which is a parasite that can be transmitted to contact with that. Other pets, we talk patients about reptiles, chickens, birds - we do not want the type of animals in the home. If they are in the home, they should be in a room that is completely separate from where the transplant recipient is, that they do not go into. They should never be involved in any component of cleaning the cage, feeding those animals or being any sort of direct contact. Those animals should not be out of their environment and around the house in a situation where you could be in contact with any places they have been. We're very, very stringent about less typical animals. Those are kind of the general guidelines that we give. There are always other specific questions that come up about certain vaccines and things like this.

Caller: Right. Okay. That's great. One more question. What about washcloths and towels and basically having your own set that nobody else uses? And do they have to be washed separate from other laundry?

Dr. Saullo: You definitely should have your own. I typically tell my patients too, I prefer when they're using soaps, particularly with soaps in the shower, that they do more of the pump than the bar soap. There is always the potential that with bar soap you are putting on your body. If there's some sort of contamination, it stays on that soap bar, or there's a potential that someone in the family would then use that same soap bar, whereas with a pump that’s less of that issue. I do prefer that my patients use the pump soaps as opposed to the bar soaps. And most definitely, you should have your own wash rag. You should have your own towel. I would definitely watch those on a regular occasion. They don't necessarily have to be separate from other family members' towels and wash rags in terms of the washing, just making sure that you're doing the normal standard cycle. In your washing machine you're using, the washing detergent and then you're drying those adequately in the dryer.

Caller: Okay, great. Thank you very much.

Dr. Saullo: Same thing also, just along those lines of thinking and being smart about this, in the bathroom at your home, oftentimes a lot of us will have the towel that hangs to the left of the sink that everybody dries their hands on. I really discourage that especially with transplant patients, having paper towels there or some single-use napkin or something that you use your own that you can discard after each time to avoid that issue of kind of cross-contamination with people.

Caller: Thank you. That's great. Thanks.

Jenny: Great answers and great questions. Thanks. Caller, go ahead with your question.

Caller: Hi. I just have a follow-up question to the pet question. So how long after your transplant then would you be able to pick up after, say, your dog? Are we talking 60 days? Or when you take your dog for a walk, like how long can you not pick up after your pet?

Dr. Saullo: Well, definitely in that early period, the first 30 days to three months, if you can find someone else to do it. I mean, it's an opportunity for you to get out of something J. Even in that period, sometimes, especially after that first 30 days, we have people that are feeling great and they're out and they're walking their dog and maybe their caregiver is not there or someone there to help them. We would just say in those scenarios if that is going to happen and you do have to do that, you wear gloves when you do that, you discard the gloves and then you wash your hands with soap and water after you do that.

I'm not saying you can never do that and even after that first 30 days if it's something that you have to do. You just have to be mindful of it and wear gloves and wash your hands. Be careful when you're doing that. I'd say certainly after the six-month mark, you're not going to be able to talk anybody in your family into doing that anymore. You're going to do that on your own. But in that shorter period after that, first 30 days in that three to six-month period, as long as you're being smart about your hygiene and doing these things, as I mentioned, then that certainly is acceptable.

Caller: Okay, thank you.

Jenny: Okay, great. Thank you. Okay. I know we're a little overtime, but we'll have one more question. Caller, go ahead with your question.

Caller: Hi, Jenny. It's Dana Holmes. Thanks so much for having this topic today. Dr. Saullo, this has been such an eye-opening discussion. You have shared a tremendous amount of information for the myeloma patient community, and I thank you for that. Does every myeloma center have an infectious disease specialists on board that you know of? I'm specifically meaning like the big research centers, the academic centers, not the community centers, because it's just fascinating to me. I think we should if we don't.

Dr. Saullo: Transplant infectious disease is an evolving field, but I think most -- and I can't speak for every center, but most large transplant centers do. They do have a transplant -- in fact, some have ones that are really specialized to hematopoietic cell transplant itself, and others such as myself, we really kind of cross the lines of a solid organ and stem cell or hematopoietic cell transplant. Those larger academic centers, I would say, do. They do have one to many involved in this patient population.

Caller: I think that's an important aspect for patients to consider once they're planning a stem cell transplant to really inquire about this member of their team because I really think it's critical after listening to your discussion. I say this because recently, in one of our online groups, a patient had asymptomatic flu before receiving their high dose of melphalan. And unfortunately, he wasn't pre-tested for it. And he passed away a few days into the stem cell transplant process because of the flu. It was really, you know, that's sad to hear and maybe that could have been avoided, maybe not. But it's certainly something for patients to be aware of, to inquire about these types of things.

Regarding the flu, Doctor, can either of the drugs that are out there, Tamiflu or Xofluza, be used to prevent the flu, or are they really specifically meant to be used once you've contracted it?

Dr. Saullo: Well, we certainly in situations where there's been an exposure, we'll use it as a component of post-exposure prophylaxis, the oseltamivir that you mentioned. So we will, if we have a transplant or other immune compromised host that's been exposed to flu, we will use it in kind of preventative mode. There is certainly data to support that, and there are guidelines to do that, and so we will use that. But just across the board, while there is some data in what settings that's appropriate, we don't do that as a primary preventative therapy. We don’t apply it broadly because we worry about the risks of resistance emergence, which is something we've already seen with these drugs and certainly don't want to add to that problem. But if there's been a clear exposure, typically we'll get involved and consider post-exposure prophylaxis in the form of one of these therapies.

Caller: Do you personally have a preference using the one that has been around for a long time, the Tamiflu, oseltamivir, I guess you call it, versus the new one that's out now, the Xofluza?

Dr. Saullo: I think it's a multi-pronged question. It really depends upon the scenario, I think, for a post-exposure prophylaxis. Most notably, I'm probably using more oseltamivir, but it depends upon the scenario that you're using it, I guess. They both have roles.

Caller: Okay. And you also mentioned about getting a booster of the flu vaccine. Is that a routine thing that you do, or is it really something per patient? Because you really seem to be modifying all of your approaches by patient as opposed to just broadly saying this, this or the other, which is really terrific.

Dr. Saullo: Well, for the booster, I think every institution is different. Just a caveat, this is what we are doing here. Right now at our center actually, because of logistics of trying to get insurance coverage for a high-dose vaccine for people under 65 where it's not covered by insurance, oftentimes what we end up doing is just a standard dose flu vaccine for most patients if they're less than 65. If they get that vaccine before the six-month mark because the flu season is now then I do booster them. I give them a second vaccine four to six weeks later. And that's also supported by the Infectious Disease Society of America guidelines because you're just worried that you're giving it to them at the four-month mark, let's say, their immunologic response may not be as robust and so you just kind of optimize that further.

So we don't do it in all patients, but that's one scenario where we definitely do that. But just to say there are some centers that are doing that kind of across the board, and there are some centers that are applying the high-dose vaccine across the board for the reasons I mentioned, that there is the safety and immunogenicity data that's evolving both in the solid organ transplant population and in the hematopoietic cell transplant population. It's interesting to see that evolving.

Caller: Well, thank you so much for your time. You've really shared so much incredible information for us. I appreciate it very much.

Dr. Saullo: Oh, thank you.

Jenny: Thanks, Dana. Great questions. And thank you for your answers. Amazing. Dr. Saullo, we are so grateful for you to join. It's such a practical thing that I think we don't feel like we get enough instruction on, I think, sometimes when we're going through the process. So this is just truly amazing to have you go in this much detail for us. Now I have reasons to go talk to my doctor about revaccination. Thank you so much for participating.

Dr. Saullo: Sure. Thank you so much for having me. I'll send you those links that I mentioned.

Jenny: Great. And I'll include them in our full transcripts when we conclude the show. Thank you so much. And thank you to our listeners for listening to Myeloma Crowd Radio. We invite you to join us next time to learn more about how myeloma research can help you.