Episode 33
33: Troll of Transplantation Part 1
Drs. Kevin He and Joseph Sassine tackle the “troll of transplantation”, CMV!
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Transcript
Hi everyone.
Sara Dong:Welcome to Febrile -- a cultured podcast about all things infectious disease.
Sara Dong:We use consult questions that dive into ID clinical reasoning, diagnostics, and anti-microbial management.
Sara Dong:I'm Sara Dong, your host and a Med-Peds ID fellow.
Sara Dong:Here on Febrile, we use patient cases to learn about high yield ID topics.
Sara Dong:We'll present pieces of the story of a patient's case, and then pause along the way to hear from our guest consultant.
Sara Dong:My co-host today is Dr.
Sara Dong:Kevin He.
Sara Dong:He is an Internal Medicine resident at Beth Israel Deaconess Medical Center in Boston.
Sara Dong:And if you haven't heard it already, I would definitely recommend checking out Kevin's previous episode on Cryptococcus, which is episode 17, also known as Yeastie Boys.
Sara Dong:Next I will introduce our guest today, Joseph Sassine is an Assistant Professor of Medicine and a Transplant ID physician at the University of Oklahoma Health Sciences Center.
Sara Dong:He previously completed his Internal Medicine residency at the Icahn School of Medicine at Mount Sinai and St.
Sara Dong:Luke's Roosevelt Hospital Center in New York City.
Sara Dong:This was followed by his ID fellowship at the University of Texas Health Sciences Center and MD Anderson Cancer Center in Houston.
Sara Dong:Today is part one of the Troll of Transplantation, where we're going to talk a little bit about CMV and solid organ transplant recipients.
Sara Dong:Stay tuned for part two was Dr.
Sara Dong:Camille Kotton that'll be coming out two weeks from this episode, thinking more about resistant and refractory CMV disease.
Sara Dong:All right, let's get started.
Sara Dong:Welcome to the show guys.
Joseph Sassine:Thank you.
Sara Dong:Before we dive into the case, we like to start off because as everyone's favorite cultured podcast, uh, we ask our guests, if there's a little piece of culture or something you have enjoyed recently that you would like to share with the listeners.
Joseph Sassine:Sure.
Joseph Sassine:So first, thank you for having me and I look forward to our discussion today.
Joseph Sassine:In terms of culture.
Joseph Sassine:I'm a big opera fan and I have a soft spot for the works of Bizet and Verdi.
Joseph Sassine:During the earlier stages of the pandemic, uh, the Met Opera from New York City was streaming some of its greatest works online for free, and that was a great wellness resource at least for me.
Joseph Sassine:I think now you can access them on demand for a subscription.
Sara Dong:Well I know nothing about opera, so I'll have to use your recommendations.
Sara Dong:And so today's consult question is about a seventy year old male who has had a renal transplant and comes in with abdominal pain and diarrhea.
Sara Dong:And so they would like us to help them evaluate for infection.
Sara Dong:Um, so I will throw it over to Kevin.
Kevin He:I'll get started with our case.
Kevin He:This is a 70 year old male with end stage renal disease, secondary to hypertensive nephropathy, who is status post a deceased donor renal transplant in October of 2020.
Kevin He:The serologies are CMV donor positive, recipient negative as well as EBV donor indeterminate, recipient negative who is presenting with one month fatigue, abdominal pain and diarrhea.
Kevin He:His PMH is also notable for a large B cell lymphoma, s/p splenectomy and gastric wedge resection seven years ago, for which he received six cycles of chemotherapy.
Kevin He:It has been in remission since, as well as coronary artery disease.
Kevin He:Regarding his transplant history, he underwent a deceased donor renal transplant in October 2020 with serologies pre-transplant being hepatitis B negative/ non-immune, Hepatitis A negative, Hepatitis C negative, CMV serology negative, donor CMV antibody positive, EBV negative, donor EBV indeterminate, and Toxoplasma negative, donor Toxo negative.
Kevin He:He was induced with basiliximab and was maintained on a regimen of tacrolimus, mycophenolate and prednisone.
Kevin He:His postoperative course was complicated by delayed graft function, which eventually improved.
Kevin He:His prednisone had been tapered off prior to discharge from his transplant admission, and his DSA has remained below the median range.
Kevin He:He was initially given prophylaxis against PCP with Bactrim [trimethoprim-sulfamethaxazole] and CMV with valganciclovir with the anticipated duration of the latter being six months, given his high risk CMV status.
Kevin He:Now, before we get back to the case, Dr.
Kevin He:Sassine, we wanted to pause here to discuss this last point.
Kevin He:There are two major strategies for CMV disease prevention after solid organ transplant -- antiviral prophylaxis and preemptive therapy.
Kevin He:Would you be able to give us a brief overview of the difference between these approaches and how we utilize the serostatus of the donor and the recipient to help stratify the risk of infection?
Joseph Sassine:Sure.
Joseph Sassine:So first let's, uh, remember that CMV is probably the most common infection after transplant and one of the most significant complications of transplant.
Joseph Sassine:CMV can affect the transplant recipient through it's direct lytic effects, which manifest with end organ disease directly caused by CMV, such as pneumonitis, colitis, gastritis, hepatitis, retinitis.
Joseph Sassine:As well as through its indirect effects, CMV is an immunomodulatory virus and CMV reactivations have been associated with graft rejection, graft versus host disease, and worsening immunosuppression by virtue of the virus or some of its therapies.
Joseph Sassine:Thus leading to a higher incidence of bacterial and fungal infections.
Joseph Sassine:For these reasons, it's very important to be proactive when it comes to CMV issues in this patient population.
Joseph Sassine:As you mentioned, there are two strategies that can be used and that actually are not mutually exclusive.
Joseph Sassine:The first one is prophylaxis, which is the administration of an antiviral drug to all patients who are at risk for a determined period of time after the transplant, and that duration is usually based on their risk level.
Joseph Sassine:Prophylaxis is an effective strategy in preventing direct and indirect CMV effects.
Joseph Sassine:It was proven effective in large randomized controlled trials.
Joseph Sassine:It is easy to coordinate and apply since you are following an algorithm and it has a positive impact on the indirect outcomes, such as graft loss and mortality.
Joseph Sassine:Nevertheless, with prophylaxis, you will be exposing all of your patients to the antiviral, whereas some of these patients might never develop the CMV infection or disease.
Joseph Sassine:Uh, so there's always the risk of over-treatment.
Joseph Sassine:And with that comes the risk of unnecessary toxicities and higher drug cost.
Joseph Sassine:Prophylaxis might also delay CMV specific immune reconstitution, and lastly, one should be aware of the risk of post-prophylaxis delayed-onset CMV disease, particularly in the highest risk patients.
Joseph Sassine:And the drugs currently use for prophylaxis in solid organ transplant recipients are oral valganciclovir, like your patient here, or IV ganciclovir.
Joseph Sassine:Letermovir was approved for prophylactic use and hematopoietic cell transplant recipients, but it's not yet approved for using solid organ transplantations.
Joseph Sassine:One of the trials looking into prophylaxis with letermovir in kidney transplant recipients is estimated to be completed in April 2022, so stay tuned for news on that front.
Joseph Sassine:On the other hand, preemptive therapy is based on the concept of surveillance of viremia after transplant and the administration of antiviral therapy to patients who reach a certain threshold of viremia or what we call CMV infection.
Joseph Sassine:To halt the progression of viremia and end-organ disease.
Joseph Sassine:This strategy essentially tampers down many of the disadvantages of prophylaxis by targeting therapy to the patients who are at highest risk of disease, minimizing over treatment, minimizing toxicities, and minimizing the drug costs.
Joseph Sassine:However, a strategy that's purely based on preemptive therapy would miss some cases of CMV end organ disease that are not preceded by viremia.
Joseph Sassine:And most notably here, you're talking about GI disease, so colitis and gastritis, which can be seen with undetectable viremia in the peripheral blood.
Joseph Sassine:This strategy, the preemptive strategy, also relies on the availability of sensitive CMV testing.
Joseph Sassine:Uh, currently we rely on quantitative nucleic acid amplification testing, as opposed to pp65 antigenemia detection in, in older days.
Joseph Sassine:And that used to rely on the number of lymphocytes present in the peripheral blood.
Joseph Sassine:You also want your CMV test to have a quick turn around time to allow for a quick and rapid response.
Joseph Sassine:So you would want 24, 48 hours at most in terms of, uh, turnaround time.
Joseph Sassine:In real life, we actually use a mix of both, uh, prophylaxis and preemptive therapy.
Joseph Sassine:This is why I said earlier they're not necessarily mutually exclusive.
Joseph Sassine:What proportions of each strategy, uh, are used, depends on the individual patient risks.
Joseph Sassine:As a general principle, the major risk factor for CMV disease after solid organ transplant is a qualitative or quantitative deficiency in global immunity and / or in CMV specific immunity.
Joseph Sassine:To estimate the patient's risk, we usually measure pre-transplant serologies for both the donor and the recipient.
Joseph Sassine:There are certain assays that measure CMV specific cell-mediated immunity.
Joseph Sassine:The use of those assays in the pre-transplant stage is still investigational, we will come back to those a little later.
Joseph Sassine:The highest risk group when you measure serologies, is going to be the recipients who are seronegative but to receive an organ from a seropositive donor.
Joseph Sassine:And this is what we refer to as D+R-.
Joseph Sassine:The moderate risk group would be seropositive recipients, so R+.
Joseph Sassine:Within that group, those who receive an organ from a seropositive donor, so D+R+ are at higher risk compared to those who have a seronegative donor, so D-R+.
Joseph Sassine:The lowest risk group are the recipients who are seronegative and who receive an organ from a seronegative donors.
Joseph Sassine:So this is D-R-.
Joseph Sassine:Just a side note, in hematopoietic stem cell transplant, it's different.
Joseph Sassine:It's usually a recipient seropositive that's the major determinant.
Joseph Sassine:Beyond seropositivity for both the donor and the recipient, there are additional risk factors for CMV reactivation.
Joseph Sassine:These include lymphodepleting agents, such as antithymocyte globulin, alemtuzumab, quite high doses of maintenance immunosuppression, allograft rejection, especially that this is after accompanied by another round of lymphodepleting therapy, and the type of organ being transplanted.
Joseph Sassine:So lungs and small intestines are higher risk than other organs.
Joseph Sassine:The use of mTOR inhibitors, such as sirolimus and everolimus, is actually associated with a lower risk of a CMV.
Joseph Sassine:There's an interesting concept called the net state of immunosuppression, uh, which is kind of important to estimate each individual patient's risk of impact.
Joseph Sassine:There's a nice paper that addresses it in CID in 2020 by Dr.
Joseph Sassine:Jay Fishman, so I can refer to that.
Joseph Sassine:With this in mind, the AST ID COP Guidelines of 2019 recommend antiviral prophylaxis with valganciclovir, uh, usually administered at 900 mg once a day or ganciclovir as five mg/kg, ideally once a day.
Joseph Sassine:And these are doses for normal renal function, and this regimen, or one of these two agents, are recommended for high-risk D+R- patients, as well as for moderate-risk R+ patients.
Joseph Sassine:The duration of prophylaxis that is recommended varies between 3 and 12 months, depending on the level of risk of the patient, whether they high-risk versus moderate risk.
Joseph Sassine:And depending on the organ being transplanted.
Joseph Sassine:So lung and heart-lung transplants have the longest durations, and these are the ones that will reach the 12 month.
Joseph Sassine:The guidelines also provide recommendations regarding the preemptive therapy as an option.
Joseph Sassine:If logistic support is available, they also provide instructions on monitoring intervals.
Joseph Sassine:They do not provide a specific viral load threshold to initiate therapy, but they rather recommend this threshold be assay specific, center specific, and risk specific.
Joseph Sassine:Some patients might require longer prophylaxis and/or monitoring than the recommended duration.
Joseph Sassine:So we have to keep an open mind with those numbers, but particularly if they receive further lymphodepleting therapy for the treatment of rejection.
Kevin He:Thank you, that was a very helpful outline.
Kevin He:Looking at the specifics relevant to our patient, and just for some additional context, he completed his valganciclovir after the six month duration of prophylaxis in April when he was transplanted in October of the preceding year.
Kevin He:And in June, about two months afterwards, he began to have this constant generalized abdominal pain, fatigue, and for the last month, persistent, non bloody watery diarrhea.
Kevin He:Now this constellation of symptoms prompted him to present to the ER.
Kevin He:In the ED, he was noted to have creatinine elevated to 1.5 from baseline of 0.9 to 1.1.
Kevin He:Leukocytosis to 13.8 with a total neutrophil count of around 13,000, and a total lymphocyte count of 740.
Kevin He:Bicarb was 11, anion gap of 19, as well as LFTs notable for a mild transaminitis, ALT of 73 and AST of 101 and alk phos 123, and a T-bili 0.6.
Kevin He:His LDH was 345 and he was a little hypoalbuminemic to 3.4 and his lactate was elevated at 2.6.
Kevin He:His tacrolimus trough was drawn and it turned out to be 4.4.
Kevin He:His UA was not pyuric and they did get some blood and urine cultures that are pending.
Kevin He:A little bit of additional history for this patient.
Kevin He:He was born and raised in Massachusetts and now lives in Boston.
Kevin He:He never traveled outside North America, but has roamed around the United States, west coast, Midwest as well as Canada.
Kevin He:He hasn't traveled at all since this transplant last year and is currently retired, but used to work at an office desk job.
Kevin He:Previously did have a pet cat, but the cat's now staying at his children's since his transplant and he's been being diligent and avoiding raw foods.
Kevin He:He's never used tobacco.
Kevin He:Doesn't drink alcohol and uses no recreational drugs.
Kevin He:And when you go and talk to him, he's not in distress, but a little uncomfortable when his abdomen is palpated.
Kevin He:He's a little bit tender non-specifically without any signs of guarding or rebound.
Kevin He:He's not fluid overloaded.
Kevin He:In fact, he appears a little bit dry and a RUQ ultrasound obtained in the ED illustrates some cholelithiasis, but no hepatobiliary ductal dilatation and no signs of cholecystitis.
Kevin He:Now with all of these details together, we just wanted to see what you're thinking about so far and while we certainly suspect that CMV is probably the issue here, we do want to keep an open mind about what should be on the infectious diseases differential for diarrhea in a solid organ transplant recipient.
Joseph Sassine:Great.
Joseph Sassine:So certainly here CMV remains a concern, particularly with the entity I mentioned earlier, post-prophylaxis delayed onset CMV.
Joseph Sassine:And this usually occurs in D+R- patients in the first three to six months after completion of prophylaxis, which is in contrast with a truly late onset CMV disease that can occur years after transplantation.
Joseph Sassine:There are various efforts that can be done to prevent this, including close clinical follow up, and early treatment when symptoms occur like here, uh, or routine viral surveys after completion of prophylaxis, further prolongation of antiviral prophylaxis, but that usually comes at the expense of, uh, significant myelotoxicity, and/or immunologic monitoring at the end of prophylaxis and thereafter, usually with things like lymphocyte count, CD4 count, or CMV specific cell-mediated immunity.
Joseph Sassine:To get back to your original question, the differential diagnosis of diarrhea and solid organ transplant recipients, as you can imagine, it's very broad.
Joseph Sassine:To follow the classical scheme of infectious versus non-infectious, infections include bacteria.
Joseph Sassine:C diff is a big one.
Joseph Sassine:Campylobacter, Salmonella, Aeromonas, E.coli, bacterial overgrowth.
Joseph Sassine:Viruses, obviously such as CMV, but also the GI viruses, Norovirus, Adenovirus, and the others.
Joseph Sassine:And parasites.
Joseph Sassine:The classic Giardia and Entamoeba, but also the traditional GI opportunistic parasites.
Joseph Sassine:So Cryptosporidium, Microsporidium, Cystisospora, and Cyclospora.
Joseph Sassine:Keep in mind that these patients can have noninfectious causes of diarrhea.
Joseph Sassine:Uh, mostly medication-related.
Joseph Sassine:Immunosuppressives such as mycophenolate, tacrolimus, sirolimus, cyclosporine, and just plain other non immunosuppressive medications.
Joseph Sassine:Diarrhea can also be a manifestation of graft versus host disease or post-transplant lymphoproliferative disease.
Joseph Sassine:For the sake of time, I will not go into the timeline of infections after organ transplantation, but there's a nice comprehensive figure in again, Dr.
Joseph Sassine:Fishman's review of infections and organ transplant recipients in NEJM back in 2007, and I think that still holds up to this day.
Kevin He:Thank you for that excellent differential.
Kevin He:Now diving into the diagnosis for our patient.
Kevin He:The CMV viral load was obtained and did return at 6.25 log or about 1.7 million copies/ml.
Kevin He:Would you be able to give us a quick overview about CMV disease and its distinction from infection, and how do we put this case together?
Kevin He:And what, if any, additional workup would you suggest at this point now that we have this information?
Joseph Sassine:Sure.
Joseph Sassine:So I think it's always important to define the disease entities you are dealing with.
Joseph Sassine:While most of these definitions are actually designed for clinical trials, to agree on standardized definitions that would allow studies to be comparable, I think they are very useful for our daily clinical practice, uh, particularly to guide us in our diagnostic approach.
Joseph Sassine:For CMV and transplant patients, there's a landmark definitions paper that was published in CID in 2017.
Joseph Sassine:In this paper, CMV infection is defined as virus isolation, or detection of viral proteins or nucleic acids in any body fluid or tissue specimen.
Joseph Sassine:When this specimen is the blood, then the assays can measure virus in the plasma, serum, or whole blood-- we talk about viraemia, which is culturing virus from the blood.
Joseph Sassine:Antigenemia, which is detecting the pp65 antigen that's specific for CMV.
Joseph Sassine:Or DNAemia, which is detection of CMV DNA, which is the most common technique nowadays.
Joseph Sassine:CMV disease includes end organ disease caused by CMV, such as pneumonia, GI disease, hepatitis, retinitis, et cetera, as well as CMV syndrome, which is an entity that is only described in solid organ transplant.
Joseph Sassine:And that includes detection of CMV in the blood with at least two of the following-- a fever, new or increased malaise or fatigue, leukopenia and neutropenia, atypical lymphocytes (more than 5%), thrombocytopenia, elevated AST or ALT to twice the upper limit of normal.
Joseph Sassine:The AST ID Guidelines summarize those definitions, including the ones for proven and probable end organ disease in their first table in the guidelines.
Joseph Sassine:To use those definitions would make it easier to determine what diagnostic workup is needed.
Joseph Sassine:With our case here, we do suspect CMV GI disease.
Joseph Sassine:The approach would be endoscopic examination would be necessary.
Joseph Sassine:We rely on the presence of symptoms, the presence of macroscopic mucosal lesions, documentation of CMV in the tissue either by histopathology, immunohistochemistry, culture, or DNA hybridization techniques to determine a proven or definite GI CMV disease.
Joseph Sassine:If you just have symptoms with documented CMV in the tissue, but without microscopic mucosal lesions, that would make it a probable GI CMV disease.
Joseph Sassine:Now that distinction might be more important for clinical trials rather than the clinical practice, but the definitions help you know what tests to order and that to diagnose GI CMV disease, you do need an endoscopic evaluation, both microscopic and tissue.
Joseph Sassine:Documenting CMV in the blood alone is not sufficient to diagnose the CMV GI disease.
Kevin He:I see.
Kevin He:So the patient ultimately actually after discussion between the primary team and some of the consultants did not undergo a colonoscopy or endoscopic evaluation given the degree of his viraemia and the symptoms that he was having, as well as, his CMV D+R- status prior to transplantation.
Kevin He:He was initiated on induction therapy due to the high clinical suspicion for end organ disease due to the constellation of symptoms he was coming in with.
Kevin He:Would you be able to teach us a little bit about these CMV treatment regimens, especially the differences between induction and maintenance therapy.
Kevin He:When do you make the transition and when do you stop maintenance after that?
Joseph Sassine:So first let's talk quickly about the available agents.
Joseph Sassine:The first line agents are ganciclovir and that would be dosed at 5 mg/kg IV every 12 hours or valganciclovir, which has 900 mg PO every 12 hours for patients with normal renal function.
Joseph Sassine:It is recommended to preferentially use IV ganciclovir for patients with severe life-threatening disease, for those with a very high viral load, and those with a questionable GI absorption.
Joseph Sassine:For mild to moderate disease, oral valganciclovir and IV ganciclovir are considered equally effective.
Joseph Sassine:There was a randomized trial establishing this non-inferiority back in 2007.
Joseph Sassine:For the patients who can not tolerate ganciclovir or valganciclovir, and that's usually because of cytopenias, or for those patients who fail to respond to these agents, and here we would be going into their refractory resistant CMV chapter, second line agents include foscarnet or cidofovir.
Joseph Sassine:These agents are reserved for the second line due to their significant nephrotoxicity.
Joseph Sassine:And just to get an idea of the nephrotoxicity with foscarnet, there's a study out of Johns Hopkins in 2016, showed that 50% of the patients who received foscarnet for refractory resistant CMV developed renal dysfunction by the end of treatment and 28% after 6 months.
Joseph Sassine:Now for these folks who failed to respond to ganciclovir or valganciclovir, a new agent maribavir was recently approved by the FDA in November 2021 with a much better safety profile.
Joseph Sassine:So that's an exciting development.
Joseph Sassine:There have been case reports using letermovir as a second line agent off-label.
Joseph Sassine:I personally would not use it in the setting of active, viral replication due to the high risk of resistance development.
Joseph Sassine:As you mentioned, there are two stages of therapy.
Joseph Sassine:They call them induction and maintenance.
Joseph Sassine:You can think of induction as the full dose therapy stage.
Joseph Sassine:Here, you administer antivirals at the full therapeutic dose, which I just mentioned.
Joseph Sassine:Maintenance is essentially a secondary prophylaxis phase to prevent early recurrence of CMV.
Joseph Sassine:There is no preset duration or blanket duration for induction therapy.
Joseph Sassine:In the valganciclovir trial I mentioned earlier, they limited therapy for three weeks and a significant proportion of patients still had viremia by three weeks, suggesting that these patients probably needed longer durations of antiviral therapy.
Joseph Sassine:This is why the AST ID Guidelines list three criteria that you need to meet before ending induction therapy.
Joseph Sassine:The first one is resolution of clinical symptoms.
Joseph Sassine:The second is virologic clearance below a threshold negative value, and this value is a test specific, based on weekly lab monitoring either with a quantitative nucleic acid amplification assay, or if you still use pp65 antigenemia.
Joseph Sassine:And they defined that as needing two consecutive results or a single negative, if you're using a highly sensitive assay.
Joseph Sassine:The third condition you have to meet is a minimum of two weeks of antiviral treatment.
Joseph Sassine:So once you meet those three conditions and you come, you complete full dose antiviral treatment, the guidelines state that secondary prophylaxis may be considered in certain high-risk patients.
Joseph Sassine:And here you would be using the prophylaxis doses as compared to the treatment doses, so once a day instead of twice a day for a normal renal function.
Joseph Sassine:The duration of antivirals and the stages are defined by the guidelines.
Joseph Sassine:Different centers use different approaches.
Joseph Sassine:Most of them will use something between one and three months.
Joseph Sassine:It also depends on the individual patient's situation, particularly in regards to lymphopenia.
Joseph Sassine:Some centers are starting to CMV specific cell-mediated immunity assays to guide that decision.
Joseph Sassine:There was a retrospective study published in CID in 2017, looking at secondary prophylaxis with valganciclovir.
Joseph Sassine:It showed the reduction and relapse with a hazard ratio of 0.19.
Joseph Sassine:So it was a significant reduction.
Joseph Sassine:Uh, but this was only in the first six weeks following treatment completion.
Joseph Sassine:The benefit did not extend beyond six weeks of secondary prophylaxis.
Joseph Sassine:I think this is still an area that deserves more investigations to determine the optimal approach and how to incorporate the use of CMV specific cell-mediated immunity and allow for CMV specific T-cell immune reconstitution.
Joseph Sassine:Before concluding the treatment chapter, there are a few more interventions to mention.
Joseph Sassine:A cautious reduction in immunosuppression should be considered, especially in moderate to severe disease.
Joseph Sassine:And usually that comes in collaboration with our transplant colleagues, because you want to weigh this against the risk of rejection.
Joseph Sassine:You can switch from IV ganciclovir to oral valganciclovir once there is clinical and virologic improvement, even if you have not competed, uh, full dose therapy yet.
Joseph Sassine:And as long as you don't have concerns for GI malabsorption.
Joseph Sassine:You should dose adjust ganciclovir and valganciclovir based on renal function, but you should not adjust them down if your patient develops neutropenia or leukopenia or cytopenias.
Joseph Sassine:Under dosing is actually a risk factor for resistance.
Joseph Sassine:So if you still would like to use those agents, you can support with growth factors or a switch to a second line agent.
Joseph Sassine:Intravenous immunoglobulins, uh, or CMV specific immunoglobulins may be considered for patients with life-threatening disease, for patients with CMV pneumonitis, or those who have hypogammaglobulinemia.
Kevin He:Thank you.
Kevin He:So as you've discussed, the patient was induced with intravenous ganciclovir, excuse me.
Kevin He:And his diarrhea did improve within one week of ganciclovir initiation.
Kevin He:His viral loads fell from 6.25 log at the outset, to 6.2, 5.3, and then 3.9.
Kevin He:Eventually falling to undetectable levels by about six weeks after initiation of induction therapy.
Kevin He:He was ultimately discharged home from the hospital with a peripherally inserted central catheter to continue his IV ganciclovir.
Kevin He:And after his CMV viral loads were undetectable two times in a row, uh, after the seven total weeks of induction, he was eventually transitioned to maintenance valganciclovir.
Kevin He:He continued the maintenance valganciclovir for about another 10 weeks.
Kevin He:As you said, he eventually discontinued it.
Kevin He:And since then bi-weekly monitoring for CMV did not show any recurrent viremia.
Kevin He:His monitoring was then discontinued after two months.
Kevin He:So overall a good outcome.
Kevin He:To end the episode, there is always some exciting news in the transplant ID world, and you alluded to a little bit of this earlier.
Kevin He:Would you be able to tell us about the latest in CMV care or new therapies available for our patients?
Joseph Sassine:There are some recent exciting developments in the CMV world and I think a great potential for more exciting news in the future.
Joseph Sassine:The most recent update is, as I mentioned earlier, the approval of maribavir for refractory or resistant post-transplant CMV.
Joseph Sassine:And that as a welcome option, especially in regards to its overall favorable safety profile.
Joseph Sassine:Some areas where we might hear news in the near future or where we need to better develop our understanding-- the use of letermovir in organ transplant recipients.
Joseph Sassine:I mentioned the ongoing primary prophylaxis trial.
Joseph Sassine:We also need to better understand the place of letermovir in secondary prophylaxis in, both in organ transplant and hematopoietic cell transplant.
Joseph Sassine:Uh, we also need to find the best way to incorporate the use of CMV cell-mediated immunity assays in our daily clinical practice.
Joseph Sassine:The use of adoptive immunotherapy for treatment, particularly using CMV specific cytotoxic T lymphocytes.
Joseph Sassine:This is mostly a field of investigation in hematopoietic cell transplant recipients.
Joseph Sassine:Finally, I recently came across a very interesting paper published earlier this year.
Joseph Sassine:It's more a hematopoietic cell transplant paper.
Joseph Sassine:They actually looked at circulating cell-free DNA profiling in those patients and how this can be used to inform all the major complications of a hematopoietic cell transplant, including GVHD, disease relapse, but also infections by plasma virome screening.
Joseph Sassine:So I just found this to be very cool.
Joseph Sassine:At the end, I want to have a special mention and recognition to my mentor, Dr.
Joseph Sassine:Roy Chemaly, who has taught me everything I know about CMV and, uh, and has accompanied me in developing that the interest of mine.
Sara Dong:I've loved these, uh, shout outs to people's mentors.
Sara Dong:A big thank you to Kevin and Joseph for joining me today.
Sara Dong:We'll have also a second CMV episode that's going to come out in two weeks.
Sara Dong:Like the past couple of episodes, I just want to do a quick plug for our Febrile survey, which we're conducting to better understand how you use Febrile to teach and learn, but also to help us understand what to do to improve for future episodes.
Sara Dong:The survey is voluntary, anonymous, it should only take about 5 to 10 minutes.
Sara Dong:You can find the link to the survey on our Twitter page, on the website or in the description link for the episode.
Sara Dong:I'll just mention our usual disclaimer.
Sara Dong:All presented patients on this podcast are inspired by patient experiences, but cases are constructed or significantly altered and de-identified for learning purposes.
Sara Dong:Please don't forget to check out the website, febrilepodcast.com, to find "Consult Notes", which are written complements to the show with links to references as well as our library of ID infographics.
Sara Dong:Please reach out if you have any suggestions for future shows or want to be more involved with Febrile
Sara Dong:Thanks for listening.
