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Forest W. Arnold, DO, MSc: Hello. I'm Dr Forest Arnold. Welcome to Medscape's InDiscussion series on respiratory syncytial virus (RSV) in adults. Today we'll be discussing RSV and immunosuppressed patients who have had a bone marrow transplant or are receiving CAR T-cell therapy. Dr Melody Smith is currently an assistant professor of medicine in the Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University School of Medicine. Welcome to InDiscussion.
Melody Smith, MD, MS: Hi, Dr Arnold. Thank you for having me. I look forward to discussing infectious complications following bone marrow transplant and CAR T-cell therapy, specifically focusing on RSV. Thanks for having me here.
Arnold: Great to have you. Dr Smith, we're familiar with RSV in pediatrics, but it is relevant in adults, too. Every year, approximately 17 0- to 4-year-olds are hospitalized per 100,000 population. Adults are only about 3 per 100,000 population. But for adults older than 85, the rate is more like 9. And this past year it peaked at 17, which is the baseline rate of those 0- to 4-year-olds. The elderly are vulnerable because their immune systems are down, and another vulnerable population is the group undergoing bone marrow transplantation. Who is a typical patient that you see in your practice?
Smith: In my practice, I focus on patients who have received bone marrow transplants, both allogeneic and autologous bone marrow transplants (allogeneic being bone marrow transplants from donors, and autologous being bone marrow transplants from the patients themselves). I also take care of patients who received CAR T-cell therapy. In my outpatient practice, though, my focus is on autologous transplants and CAR T-cell therapy.
Arnold: How do you make the diagnosis of RSV?
Smith: An RSV diagnosis can be made with polymerase chain reaction (PCR), where we can do a swab of the patient's nasopharynx or their nostril. From that we can see if we're able to amplify the virus. This is something that's really important to evaluate in our patients who have either type — allogeneic or autologous bone marrow transplant — or CAR T-cell therapy, because these are patients who are immune suppressed due to the treatment they've gotten for their blood cancers. But in addition to that, after going through autologous or allogeneic bone marrow transplant, as well as CAR T-cell therapy, they're given additional types of chemotherapy as a part of this treatment that suppresses their immune system. They're more at risk for upper respiratory viral infections, including RSV.
Arnold: I see. And you're using nasopharyngeal swabs, correct?
Arnold: We're all familiar with that from COVID-19. I assume you're also using bronchoscopy samples as well.
Smith: Right, for patients who have more lung involvement, when we see findings on our chest x-rays that are concerning for RSV and patients are having more difficulty breathing. Or when we really want to make an accurate diagnosis we use bronchoscopy, with bronchial washings, to be able to identify the virus. That is important as well for the treatment process.
Arnold: What morbidity do you see with RSV, and do you see mortality attributed to RSV in your patients?
Smith: I would say that mortality in our patients due to RSV is not as common in the adults that I treat as in some of my pediatric transplant or cell therapy colleagues. It's not something that I see often, that patients die because of complications of RSV. But if it goes untreated or if the treatment is delayed, that can definitely increase the potential that a patient may have complications leading to mortality.
Arnold: Could you give us an example of somebody you see?
Smith: I would give an example of a patient who had received an allogeneic or a donor bone marrow transplant — for example, a leukemia indication. They had received conditioning chemotherapy and got the bone marrow transplant. They're discharged because they've recovered from the bone marrow transplant. But on routine follow-up, we noticed that they're having increased difficulty breathing; some stridor, perhaps; and also may have decreased oxygen levels. We get a chest x-ray, which shows concern for RSV or viral pneumonia. This is the type of patient that we would bring back into the hospital to evaluate further. Oftentimes, we do a nasal swab to evaluate for RSV, but we would also very promptly consult our pulmonary colleagues to plan for a bronchoscopy where we'd get those washings. I would say that most often if the patient is clinically stable, we would plan to not initiate treatment unless the respiratory swab was positive. If it were positive, we would start ribavirin. We try to get the bronchoscopy as soon as possible related to the initiation of ribavirin so that that bronchoscopy yield is not diminished by the patient starting on treatment.
Arnold: The immunocompromised state of these patients certainly justifies treatment. It's just that there's no FDA-approved treatment for RSV. Ribavirin, you mentioned, is FDA approved for hepatitis C, which is not so relevant here. How do you administer the ribavirin?
Smith: Generally, it's not inhaled. It's an oral pill.
Arnold: And tolerated.
Smith: And tolerated. Yes.
Arnold: And much easier to give than the hoods you have to get with the inhaled. That's kind of a nightmare.
Smith: In the pediatric population, they seem to do a lot more of the tents. From my understanding, it's the inhaled ribavirin.
Arnold: I think you're right. Just the frequency of it makes everybody more comfortable with that administration. So for adults, there are four pharmaceutical companies working on an adult RSV vaccine, and one was just approved on May 3. Is there a role for the RSV vaccine in your pretransplant preparations?
Smith: I think that's something that we would need to evaluate. We don't routinely give vaccines as prophylaxis against potential infections that patients may experience in the pretransplant setting. Those vaccines are often given — not only the standard vaccines but vaccines for infections that the patients may be more at risk for — they're generally given a year post-transplant. A study would need to be done to look at whether a pretransplant vaccination would be beneficial, reducing morbidity and mortality in the transplant or cellular therapy population. But routinely, I would say, the vaccines are most often given a year post-transplant, once patients' immune systems have recovered such that they can mount a vaccine response. The reason I say that is if we were to give a vaccine in the pretransplant setting, would we give conditioning chemotherapy or radiation to prepare the patient for the transplant that would wipe out that immune response and they would need it again later? The pretransplant window would be not a long-lasting response in terms of immunity in the transplant population.
Arnold: Do you already have a policy for your influenza vaccine that might be similar to what we'll see for RSV in the future?
Smith: We give those at a year post. We don't give them in that first year post-transplant.
Arnold: Then not pre-, or if they get it pre-, it just happens to be with their usual standard of care.
Smith: Right. By their usual standard of care.
Arnold: So far we've heard that RSV causes significant morbidity and even mortality in the bone marrow transplant population. There's no treatment available, but sometimes — rarely — ribavirin is used off-label. And prevention is important. And now with an adult RSV vaccine available, we'll have to figure out how to integrate it into this population.
Arnold: So if a patient is scheduled to get a transplant and it's just a couple of days before they're going to get hospitalized and they get RSV, how does that interfere with the transplant schedule?
Smith: That's a difficult position that we're sometimes placed in with RSV or other respiratory viruses. What we do most often is delay the transplant until the patient has clinical and symptomatic recovery, because we know that the patients coming in, even just days before the transplant, if they're positive for one of these viruses, that in the setting of further immune compromised status — that a viral infection which in a healthy individual could resolve, maybe even just be treated symptomatically — in our patient population it could even increase the potential mortality of the transplant. We would certainly delay until the patient has clinical recovery. Most often we look for clinical recovery. Sometimes with these viruses, the test can show positive for a while, even when the patient is clinically improved. The clinical symptoms are the thing we most monitor for.
Arnold: Okay. And some unfortunate people get their transplant and then it's followed by RSV. How does that affect their course?
Smith: We would work very closely with folks like you, our infectious disease colleagues, to do everything we could to treat. We would talk about giving the therapy that is available, such as ribavirin, and including optimizing symptomatic treatment for the patients, hopefully without decompensation that would require ICU care. It would definitely require closer monitoring of the patients and working very closely with our infectious disease colleagues.
Arnold: What if the transplant had been 6 months, a year, a year and a half ago? How would that affect their course?
Smith: If it's a year or a year and a half post-, that's where we could start thinking about therapy and then also incorporating potential vaccines for patients who are at high risk. The options for treatment would be still available but not as concerning. The patient population is not as, let's say, delicate as an early time point post-transplant or with the delay that would be incurred in the pretransplant state.
Arnold: Okay. And I know that some of these late posttransplant patients go on to get graft-vs-host disease (GVHD).
Smith: Yes, and that's a good point. I was just about to bring that up.
Arnold: If they go on to get RSV, then tell us about how that might affect their course.
Smith: One thing I was going to mention is, unfortunately, one of the potential complications after an allogeneic bone marrow transplant is the development of GVHD, where T cells from the donor bone marrow can see aspects of the host or recipient's immune system as foreign and can attack various organs. The most common organs that are involved are the skin, the liver, and the GI tract. These patients who develop GVHD, either in the acute setting or chronic complications related to GVHD, are on immunosuppressive medications. This would also be another population of patients where if they were to develop RSV, then I would probably recommend treating that patient as opposed to just symptomatically managing them because, again, they're immune suppressed. Compared with a patient who is a year post- and has GVHD, I would probably advocate for treating them even with ribavirin off-label as compared to a patient who is 1 year post-transplant and doesn't have GVHD. Their immune system is more robust. You could probably try symptomatic management or still treat. So, definitely, a patient with GVHD is more immune compromised and has to be taken care of in that regard.
Arnold: How does having or planning to receive CAR T-cell therapy affect the course of RSV?
Smith: For our patients who are planning to receive CAR T-cell therapy, they get conditioning chemotherapy, which we touched on a little bit. And this conditioning chemotherapy is milder and not as prolonged as the therapy that's given prior to a allogeneic or autologous bone marrow transplant. The reason why we have to give these patients chemotherapy is to deplete the number of T cells in their body so that when they get the CAR T cells, the CAR T cells can expand and proliferate, proliferate and persist. What's really important to note is that we're starting to see more prolonged cytopenias; various groups have published on this. Following CAR T-cell therapy, we know that the patients are going to be lymphodepleted, so their T cells are going to be low. Those cytopenias are characterized by low neutrophil counts, which increases the risk for infections. Most commonly we're seeing that those are viral infections, including RSV. So to answer your question, essentially for a patient who is post–CAR T-cell therapy, if they were to develop RSV, I would also — particularly in a patient who's lymphopenic or neutropenic — advocate that they should have treatment and not just be managed symptomatically. Particularly if the patient has clinical symptoms that are concerning for RSV and not just a positive test.
Arnold: Is there an area of RSV — knowledge about it, or the treatment of it, or the vaccine — that you feel is really needed in the hospital with your patients?
Smith: I'm sure none of the initial studies have been done on immunocompromised patients because it makes sense that they would probably first evaluate a healthier cohort of patients when they're assessing for this vaccine. It may be of interest to understand how the long-term memory of these vaccines works in both healthy and potentially immunocompromised patients. That would help benefit not only transplanters but oncologists and those who work with other immunocompromised patients to understand how they can incorporate this vaccine. How often would patients need to receive the vaccine? How does the use of the vaccine impact hospitalizations, need for ICU care, and morbidity and mortality in patients who are immunocompromised and not in otherwise healthy patients?
Arnold: The onset of this vaccine will answer some questions — but also generate a lot.
Arnold: Regarding the isolation precautions, the CDC says to place patients in the hospital in contact isolation. I'm curious to know what they do at your institution.
Smith: All of our patients, at least at my institution, who receive a transplant are in private rooms. When they develop respiratory viruses, we put them on droplet precautions as well. If the CDC recommends contact isolation, we would do that too. But generally, for the upper respiratory infections, we do have patients on droplet precautions as well.
Arnold: It's important to call infection control because as closely as they follow the CDC recommendations, each hospital seems to be different.
Smith: I think your point about infection control is really important. There are so many different upper respiratory viral infections that patients may have, and we keep infection control very closely involved in our patients. Whatever virus they may have, as we know, sometimes these guidelines change. Not only can they be different from one institution to the other, but there may be new recommendations to come forth and the guidelines change. We generally just reach out to them when one of our patients has a respiratory virus — RSV or otherwise — so that we can make sure that we're following the most up-to-date guidelines in terms of their management.
Arnold: Right. And I think people do follow the contact isolation, and probably a lot like your place and mine, we add droplet isolation on top of it. The other variable is how long do you keep them in isolation? It's another call to infection control. How long do they want them in?
Smith: I go with what infection control says because generally they have very clear guidelines in terms of that. And the other thing that's really important about keeping the patients in isolation for an adequate amount of time, and for that requisite amount of time that's recommended, is that we want to make sure that the patients recover and they're safe and healthy, but that all the patients around them, if they were to be walking in the hall, etc., don't contract RSV or a virus like that. That could be really complicating to other patients' care. For that reason, I really do defer to our infection control in their guidance.
Arnold: Very good. Today we've had Dr Smith discussing RSV in patients who have had either a bone marrow transplant or CAR T-cell therapy. RSV may postpone therapy or prolong the course if patients have already had a bone marrow transplant. If treatment with ribavirin is used, it is off-label. And finally, isolation is contact isolation, plus whatever your specific hospital requires. Thank you so much for joining us. This is Dr Forest Arnold for InDiscussion.
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Cite this: RSV Infections in Patients Receiving Bone Marrow Transplant - Medscape - Jun 14, 2023.