← Blood, Sweat and Smears - A Machaon Diagnostics Podcast
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- [00:06]
A
Hello and welcome to Blood, Sweat and Smears, a podcast produced by Macheon Diagnostics. In this podcast series, we will be discussing thrombosis and hemostasis from the perspective of our host benign hematologist and medical director of Macheon Diagnostics, Dr. Brad Lewis. Please remember to subscribe and leave a review. With that. I'll turn it over to Dr. Lewis. Brad, take it away. Hi, my name is Bjorn and I'm sitting in for Dr. Lewis for our series five questions, where we pose five questions to physicians in and around the disease areas we work in. We hope you find these short interviews riveting or at the very least, vaguely of interest. Today I'm joined by Dr. Sara Caviani, Assistant professor of Pediatrics, clinical director of pediatrics Stem Cell and cellular Therapy Program, the clinical director of the Comprehensive Immune Deficiency and Dysregulation Clinic at the University of Chicago's Comer Children's Hospital. Thank you for Joining us today, Dr. Caviani.
- [01:07]
B
Thank you for having me. Sorry for the loud situation in the back. I'm in clinic and there's a traditional bell ringing that happens at the end of chemotherapy. And so the cowbell that you're hearing, we are not in fact herding cows here at University of Chicago who are hear.
- [01:25]
A
That's fantastic.
- [01:26]
B
Yeah.
- [01:27]
A
I mean, what a wonderful sound. All right, so our first question, and maybe this is very relevant to the ringing of the bell, but what is the best part of being pediatric BMT er?
- [01:40]
B
The constant state of fear? No, I'm just kidding. I think the best part, honestly, is getting to play an immunologist on tb. I am not an immunologist by training at all. I took an immunology course during my pediatric hematology oncology fellowship when I knew I had fallen in love with transplant. My mentor was a non malignant transplanter and I kind of knew what that was, but I was like, what is that? And just for, you know, full transparency sake, it means I take care of patients who go to transplant for non malignant disorder. So that can be anything from inborn areas of immunity, metabolic disorders, hemoglobinopathies. Like, that's what I love. I do all transplants, but that's where my heart is. So I think the best part is knowing I had to learn immunology as an oncologist, which I still don't think I know immunology, but somehow I find myself taking the most complex immune disorders to transplant. I think the respect you have to have for the immune system, the respect that you have to have for your patient's disease state in the true understanding of how those are going to come into play at any given moment. That's what I love about transplant. I never can tell what's coming next. I mean, when I think that things are going to go smoothly, they go terribly. When I think things are just going to go, like, catastrophically, the kids are flying, and so I've given up. And I think that's just pediatrics in general. It's just because they're so amazing and they're rock stars, and they can take anything you throw at them for the most part. But doing what I do in the transplant realm, it's this. This healthy respect for the role of the immune system in every aspect of how we take patients to transplant. I think that's the best part. It really is amazing. And the field only continues to grow, and our understanding only continues to grow, and it's still such poor understanding, but it's way, way better than even, like, 10 years ago when we're doing this. This.
- [03:41]
A
Okay, question number two. It seems like there is a metamorphosis that happens to hematologists, oncologists when they move into bone marrow transplant, where that becomes how they define themselves. They are BM tears. What is it about bone marrow transplanters that explains this shift?
- [03:58]
B
I have to think about this one. You're gonna get me in trouble. I feel like this podcast is gonna be released into the realm of the world, and then I'm gonna get, like, hate mail. I'm only kidding. I think he's nodding his head, by the way. I think that the unknown, and I describe it to my fellows who think I'm absolutely insane, which I definitely am, for those of you who don't know me. But it's this ability to live in the gray zone. And the art of transplant really comes down to saying, we don't know. Here's a couple tests that we can try to run on every single patient and then pick our favorite pathway and go down that realm and try to rationalize. You know, what our oncology colleagues have done so well is collaborate in numbers. So the children's oncology group is such a huge force, and the numbers, the large kind of breadth of institutions that are part of the cog, their protocols, are perfection at this point, compared to the adult world. We're nowhere near where you're going to get in terms of N and P value and all that. But COG has really changed the landscape in pediatric oncology. In transplant, it's even more complex because there's different parts of the country that do things a certain way. There's certain providers that do things a certain way. Some of us do more non malignant transplants, some of us are malignant transplant centers, some of us are cord transplant centers. You can't pick one thing. And we like to be difficult as transplanters, for sure, but I think that picking from the gray zone, the best of the gray, the darkest shade of gray, you know, to make it more black, I guess, or would you want it more white? I don't know. But kind of picking the most rational pathway that you can, you know, put together in that moment for your patient. That's what it comes down to, to do transplant. In terms of what I do in the non malignant realm, you know, a lot of the disorders that we have quite unquote the most experience with, they're still relatively new. You know, when you're looking at the huge IUIs categorization of all the immune disorders, that list grows every year. You know, every second year that they put it out, you're adding all those genes, like, where do you think those disorders? They were still there 10 years ago. And we were probably doing something to them with transplant. We just didn't have a label. And now we're coming together with different consortiums, different leadership groups, different transplant consortia. We have a little bit more data, we have more n, but it's still. These numbers are so, so small and really leaning in on each other. There's this whole like secret transplant community, right? Not everything's published, but you best believe that I will know if there's a transplanter in the world that has transplanted X disease. And I will find them and hunt them down via email and get their experience and kind of hear how things went for them. So I think it comes down to what I said earlier. There's kind of this art to being a transplanter and being okay with data extrapolation and kind of navigating the unknown to the best of your ability. I think the short answer though really is the transplanters are all so incredibly type A. And that's the bottom line, period. End of sentence. Next question.
- [07:14]
A
It's not one of the official questions, but is there a handshake?
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B
You know, maybe we should come up with one. I feel like that's, that's our task, that the next time we meet up is you and I come up with one and maybe we can post like a YouTube tutorial.
- [07:29]
A
Yeah, no, I think this is a good idea. Okay, question number three. I Once heard a hematologist describe the post BMT environment as being akin to hitting a brick with a hammer. A light tap doesn't break a brick, but a heavy swing. And that's the conditioning for bmt finds the places where the brick isn't as strong and breaks can happen along those lines. In what way does that ring true or not?
- [07:53]
B
It's interesting. There's definitely truth to the overarching principles of that statement. So I had a mentor who taught me well. He taught me everything I know, really. But he taught me that the best kind of way to feel comfortable and confident in transplanting patients with rare disorders that can be applied really across the board is to personalize your treatment. Mind you, we have like five to 10 drugs max that we can choose from in the transplant realm. But regardless, he made me, and as a fellow, literally my first year fellowship, where I don't even think I could tell you mechanism of action for most drugs, he had me sit down and go through each patient that we were taking to transplant and say, you know, what is the disease? What are kind of the conditions that you're up against? That is, what organ involvement do they have? What toxicities are you worried about in them? What are you willing to tolerate in terms of toxicity? What is the most impactful in terms of morbidity and mortality in your patient? And use that kind of backbone. And he literally made me write them down in columns. This is the disease state. These are potential organs that might be involved. This is what I'm worried about long term and kind of work back from that and say, you know what, how much damage are you wanting to do with your prep? And when I describe prep or conditioning to families, I say, you know, the point is twofold. One is to create a stem cell niche physical space, and that's kind of where you're like hammering away at those cracks and kind of pushing things away. That's creating an environment where those stem cells can go and nestle and then find their home and start to build new cells. And the second piece of conditioning, and I think this is where it can get a little challenging, is how are you going to calm your IMM to make space for those new cells? How are you going to calm your immune environment so that you can prevent graft rejection and you can prevent gbhd? Because if you don't have one or the other, if you don't have space, those cells won't have anywhere to go and they won't grow and you won't engraft. And if you're not immune suppressed enough, you're going to have a lot of the toxicities and mortality associated with transplant. So I think more than just the weaknesses in the brick, you want to make sure that you provide enough force to get in and make those cracks with the new cells. But you don't really want to demolish the building in the process, so to speak. You don't want to leave your patient with so much toxicity on the back end that it defeats the purpose. Especially in non magnet world, we really have no room for raph versus host disease. It's not a high risk leukemia patient that you're taking a transplant where you actually want those immune environments revved up against each other. You want those donor cells to really kind of like pack a punch against the leukemia in the non malignant. Most of these patients are going in without evidence of malignancy and so there's no point in having that component of revved up immune systems. So it's even more important to kind of focus on that immunosuppressive component of the prep. So I think tap cautiously I guess, and then thoughtfully in the brick building just to make sure the whole thing doesn't collapse while you're doing it.
- [11:03]
A
Question number four. How does your work touch on the other subspecialties around you as a BMT or how do you interact or cooperate with your peers?
- [11:11]
B
On any given case, I would not be able to do what I do without my colleagues. I mean within the institution as well as globally. I think that the network that we have amongst the transplant community, passing secrets, so to speak, knowledge, experience is so important and I think even more so outside the transplant world, I rely on all of my colleagues to really provide their expertise in thinking through these patients. What I mentioned earlier in terms of what is your patient in front of you doing before you even transplant them? You know, all of our patients here get consult with our immunocompromised ID doctor to the point where my nurse practitioners sometimes make fun of me because I'm so adamant about it. But you never know, you know who had a pet lizard that they were housing in their mouths for years before transplant? And you're laughing, but I'm not even joking. Our ID guy here, infectious disease guy here, he's one of my good friends, very funny. And he used to ask this question, we would go in the rooms and he would say, what pets do you have at home and what is your relationship with the pets like, what is your interaction with them? I never what I stop at what pets do you have? And I'm like, why do you ask it that way? And he's like, I kid you not, I had a patient and it's always the lizards, the like bearded dragons and stuff that we worry about with salmonella, those bad things. He would put the lizard in his mouth and the lizard would just hang out there. I mean beyond the fact that that sounds disgusting and the parent standing there and like heard that this was happening, is that's, that aside, I have now completely catered how I ask these questions. But I think that, you know, even though that's a funny story, that's kind of gross at the same time it just shows that every one of the subspecialties is thinking about a different angle of the patient and has their own experience to chime in. Our multidisciplinary clinic here at Comer for immune disorders is myself infectious disease. We have our immunology colleagues that we love, obviously rheumatology. We have a huge relationship with our GI colleagues. So many early onset IBD patients that we're sending back and forth. But also they play a big role in my transplant and post transplant life in terms of absorption, GVHD worries, all those things. So I think we all take care of these patients with a mutual respect that each of us provides kind of a different angle and different expertise and can lean in and tap into their own network of people. So at any given time, who knows how many emails are going back and forth about our patients and kind of making sure that we're all doing the right thing and thinking outside the box, which often we have to do so entirely rely on these networks of amazing people that I have around me and within the community.
- [14:06]
A
Question number five, since I'm from the laboratory, what's your biggest diagnostic challenge when it comes to pediatric bmt?
- [14:14]
B
It's a great question. I think the, the challenge often lies within the conditioning and the prep that, that we provide patients. This is kind of where my answer is going to get kind of multiple layers, so bear with me. But the conditioning and the prep that we provide, we know causes endothelial dysfunction, that endothelial dysfunction, we can label it like six different things because we're transplanters and I just told you, quote, there's an art to transplant. So we like to like sound fancy, but engraftment syndrome, veno occlusive disease, transplant associated microangiopathy, early gvhd, an inflammatory cascade from effector T cells or graft rejection, all of those things have a degree of endothelial dysfunction and they're all within a spectrum. You know, when I started here, I had a patient with very bad vod. And my. My medical director kept saying, well, what if it's pulmonary vod? That thought hadn't even crossed my mind. And there's literature to support that. That's a thing. But in my mind, it's like, what's the difference between pulmonary and then what? Idiopathic pulmonary syndrome or ips? Like, what are all these things? It's all a spectrum of dysfunction that we undeniably caused with our prep and kind of transplant process. And that, that gray zone of how do you differentiate, how do you know what to label and what very expensive drug do you use to target? For me, I have a really specific interest in graph rejection and graph failure and the role of the immune milieu at the time of all of that happening. And there was just a beautiful paper that Tony Zabolsky and the team at Cincinnati put out showing that interferon and the downstream effects of interferon are high in patients who have graft rejection. And so they used emipalumab or Gamma Fant to treat or prevent graft rejection. I mean, that's huge in our field, right? Like, can we find these patients, identify them early on, and use biomarkers like CXCL9? And yes, I'm very well aware that your lab runs that. And I promise I was not asked to say this. Those labs in a timely manner that we can an action. Oftentimes, those labs that we're sending, we don't have them back for several days to a week after. By that time, we've done 80 other things. And it's like, what made the patient better or worse? Right? Like, I'm doing 10 things at once, and then I'm layering on immune suppression or taking off immune suppression or adding drugs. I think the diagnostic challenge comes with, you know, what are you seeing in the lab, values that are readily accessible and the clinical picture of the patient in terms of what bucket you want to put them in. I think that's first, that's really challenging because they tend to really overlap. And two, how are you going to use the knowledge that we have to identify each of those things? Are you going to send a TMA screen? Are you going to send cytosines? And how quickly are you going to have that information back to act? Oftentimes we're sending all at once. I'll tell you that. We're sending TMA screens and cytokine testing, and all of that comes together and we pick the best, most reasonable path to go down. But it's really challenging. It's challenging to identify those labs in a actionable time period that's truly impactful for your patient.
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A
Yeah. If only there was a lab that did things really, really fast.
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B
Convenience, convenience.
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A
But, you know, this would be commercial. So we're going to move on to our bonus question, which is what is something you would recommend? It can be absolutely anything.
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B
Okay, I have to say two things. Can I say two things?
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A
Yeah.
- [18:04]
B
Okay, cool. The first thing is because we were talking about this before this call, because I just listened to Xiao's podcast. Is tequila over wine? Take me to my grave with it. Like, for sure, drink tequila, you will never be hungover ever again in your life. Cannot say the same thing for wine, he says. Not true. Two. Okay. I'm a big college football fan and Michigan Wolverines 2026 national champions. I tell you that. Just watch and see my recommendation by all the Michigan paraphernalia. Be a Michigan fan. We're going big.
- [18:41]
A
All right, there we go. You heard it. You heard it straight. Straight from the source here. Well, fantastic. That was really good. Appreciate your time today. Yeah, thank you.
- [18:51]
B
Thank you so much for having me.
- [18:54]
A
That's it for us here at Blood, Sweat and Smears, a podcast produced by Matrian Diagnostics. You're a reference lab and CRO specializing in thrombosis, hemostasis, and rare disease. Thank you for listening. And if you have a question or comment or there's a topic you'd like Dr. Lewis to speak to, please send us an email to blood sweatandsmeersatriondiagnostics.com that's M A C H A O-N diagnostics.com youm can follow Macheon at Twitter aiondx. Be sure to subscribe to stay in the know. Share this podcast with clinicians you think might appreciate it, and we hope you'll join us next time here at Blood, Sweat and Smears.