Hello and welcome to everyday oral surgery. This is your host, Dr. Grant Stukey. I am an oral and maximal surgeon practicing in Denver, Colorado. The goal of this podcast is to connect, learn, and inspire. In this podcast, you'll be hearing from Ole Miss surgeons all over the globe discussing ways to improve the practice of oral and maximal surgery. Most information shared in this podcast will be based on personal experience and opinions, so please supplement what you learn here with approved research studies. If you are regular follow all the podcasts, please go to our website everydayoralsurgery.com and register to receive newsletters and find links to our social media accounts. Most importantly, if you would like to be interviewed on the podcast or know someone who you'd like to hear from or if there's a topic you'd like to hear about, please email me at
[email protected]. Welcome to the episode. Thank you everyone for tuning in and listening. Today I'm with Dr. Andrew Yenzer. He's an oral and maximal surgeon practicing in North Carolina and Dr. Maxwell Lloyd. He is a hematology oncology specialist practicing in Boston. Thank you guys for joining us on the episode today. It's great to be back Grant. Hello listeners. So happy to have my brother and one of the experts on this kind of stuff for part three of our hematologic series. Max, how you doing today? I'm doing really well. It's great to be back. Always a pleasure to be chatting with you both and excited for the topics that we're going to be covering today. I am particularly happy you're here today because today we're going to be talking about hematologic malignancies and it is such a deep world of ever changing things. We guidance that having a true expert in the fields I think is going to be so helpful for our listeners as we go through stuff. You know, normal disclaimer, you know, please look up any medical advice prior to using it on a patient and verify things for yourself. I'm going to shamelessly plug a St. Louis course, the St. Louis Ole Miss Review course in October, you know, focused on the oral boards and preparation. Slots are starting to fill up and we do cap it so that we can maintain very small groups when we spend about half the course going through mock cases with about groups of about six to ten folks. So look online and sign up to join us. We're still working and finishing up the next version of the oral boards blue book. I call it the blue book because it's blue, but the Ole Miss Review book by Ready and Finley. We've been putting in a tremendous amount of effort on that and it's even better. I'm going to come out sometime this fall. Hopefully, Doug can learn with the course. I also want to give a shout out to a listener who emailed me recently. Apparently, we're big in Taiwan. So, Harley and the Taiwanese residents, thank you for listening and being fans. It's so wonderful to hear, you know, that we're got some international folks and helping to help spread medical education around the country. So, next, I want to start off with some doctor vocabulary things because I think in this section in particular, we have a lot of different prefixes, suffixes that if you understand them, it really helps you understand some of these conditions. Do you want to take us through some of the prefixes to start? Having a framework for some of this language can be incredibly helpful and it just makes understanding what the conditions are a little bit more organized. And so things like Luke or Luke O is referring to white blood cells. So, a leukocyte is a white blood cell. Lucopenia is a low white blood cells. Or leukocytosis is when you have too many white blood cells. So, that will come into play as we're talking about some conditions where the white blood cells might be too low or too high. Myel or myelot is referring to the in the bone marrow. And some suffixes that we often run into are things likeemia, which indicates a lack of something. So, in the blood, anemia is going to be a lack of red blood cells and the ending site refers to a cell specifically. So, an erythrocyte is a red blood cell. And then osus is an abnormal condition. So, leukocytosis, as we mentioned, is an elevation of white blood cells. And I think that as we get into these, there's so many of these where the wards get longer and it gets tacked on. But if you can figure these things out a lot of times, it kind of tells you where the problem is or what specific cell when it is the case. So, I think it's helpful to kind of go through that. Just a couple other to tack on what Max said. There's the word indolent. And I think about indolent as kind of meaning lazy. I'm going to use it to describe certain disease states, but a lazy kind of indolent course means it causes very little pain. It just kind of meanders along and develops. Contrasted with using the word aggressive. You know, certain hematologic aliguan disease might be pretty aggressive and quickly, you know, take over the body and spread and have systemic effects. Potiquea, and we'll talk about these a little bit, are tiny flat, red or purple spots. These are not raised. And they're usually caused by bleeding under the skin and tend to be less than two millimeters in size. We often see this when we have very low platelets or thrombocytopenia. Just a couple others. Blast. A blast refers to an immature precursor cell, a very early stage in development of blood cells. And we have this term B symptoms, B as in boy symptoms. And these are constitutional symptoms like fever or night sweats and weight loss that can be seen with a lot of these malignancies. And maybe I imagine Max people with chief complaints of some of these things if you happen to be seeing him. Max, you want to start off with one of the most common and let's start off with leukemia? Yes. So leukemia is a very broad topic and we'll get into some of the more specifics, but thinking sort of from a 10,000 foot view, it's a disease of the mesenchymal cells in the blood in the bone marrow where there's an abnormal proliferation and increased lifespan of either myeloid or lymphoid precursor cells. And so all these blood cells originate from a pluripotent stem cell. And so we think of a undifferentiated stem cell at the top of the hierarchy that can then differentiate into some of these more sub-specialized blood cells that have different functions in the bone marrow or in the body. And that can either be myeloid cell or a lymphoid cell. And that helps us to classify what type of leukemia it is that we're dealing with. Either myeloid leukemia or lymphoid leukemia and the corresponding characteristics and treatments of those conditions. And so myeloid cells, as you go through differentiation of the cell, the common myeloid progenitor cell can differentiate into things like a megochariocyte, which then goes on to help us develop platelets. It can differentiate into an erythrocyte and red blood cells. It can differentiate into a myeloid blast, which then differentiates into other various types of granulocytes. So we have things like neutrophils, vasophils, eosinophils, macrophages. Those are all cells that arise from the myeloid lineage. On the other hand, we have the lymphoid lineage. And so from that pluripotent stem cell, it can differentiate into a common lymphoid progenitor. And from the lymphoid lineage, we get our B cells, our T cells, and our natural killer cells. So we have cells of the immunity of the immune system that also take residence in our lymph tissue and help us think about the nomenclature of these lymphoid cells that often circulate through the body and are part of our immune system, where we have B cells generating antibodies against foreign threats or T cells, mediating cytotoxic killing of foreign antigens and microbes. So those are the two main branch points of these cells that we see in normal bone marrow and blood cell development that then help us think about the types of leukemia that could arise in what we're dealing with from there. Kind of like the other pathology, Max. I like to picture, we have the normal kind of flow of everything, like a factory or a production line. And then you can have problems at any point along there. So breaking it down into those categories and we can think about what if we have cancer of any of these particular things or further back in the process earlier in development and then what happens to the bone marrow in the factory space when these things do have problems. What happens when somebody develops leukemia systemically? Well first we get an increasing amount of circulating leukocytes, for example, if we pick that as the problem cell, then those kind of build up in the blood. And then the bone marrow with these issues becomes overtaken and swamped by these cells, which stops the bone marrow from doing its job, picture the factory getting destroyed. And if that happens to a high degree, it leads to bone marrow failure. And here we have a term that often manifests called pan cytopine. And that means a decrease in all the types of blood cells. And these destruction of the bone marrow and the lack of function mean our normal cells are not going to get made and our body is going to lose those functions. And often present with a pan cytopine, although whatever the cell or problem is in the leukemia will tend to be very, very high on testing. When these abnormal cells are circulating around a body, it can also get deposited in almost any of our major organs, right? Things like the liver, the spleen, the lungs, and cause destruction of the normal things that those organs do. And so for general characteristics of all leukemias, we're going to have increased amount of circulating leukocytes or the problem cells. We can have infiltration of the bone marrow. And I mentioned some of those other sites of common infiltration, but those can also be the skin and the lymph nodes. People present with signs like fatigue, dyspnea, problems breathing, malaise, just feeling that. Beleding, things like epistaxis or random nose bleeds, bruising easily. Being from the gums, from brushing their teeth or after teeth extraction or procedure, infections because their body can't fight those off, fevers, headaches. And when we have that progression to bone marrow failure and things get worse, we can get leukopenia as part of that pan cytopineia picture and really struggle with dealing with infections as well as thrombocytopenia, maybe patekia and problems with bleeding. So it's kind of this nasty progression through as our body just gets sicker. Just kind of bring back some flashbacks to reading deep diving some of this stuff for you, Grant. Oh, for sure. Yeah. This is a good review. It's good to start basic and start building on that. Yeah. I think so. I think having that foundational understanding on what's you plugging the information. Next, would you want to take us through some of the, start to talk about the subtypes of leukemias? Yes. You had mentioned thinking of the bone marrow as a factory, which I think is a great analogy in helping to consider how the blood cells are made and then utilized by the body in a healthy way. And another analogy that I've heard and liked is thinking of the bone marrow as a garden where you need the right environment in building blocks and nutrients for a garden in order for healthy flowers or produce, in this case, blood cells to grow and thrive. And so there are a number of things that can go wrong with the garden. If you don't have the right nutrients or building blocks, say iron deficiency can lead to a troubles with building red blood cells, then you can have trouble with your garden growing the right healthy cells that your body needs to function appropriately. And one way to think about leukemias or other blood cancers is sort of like weeds in your garden. These are not the kind of flowers or things that you want growing in your garden. They're infiltrating the soil and crowding out the healthy, normal development of things that you do want in your garden. And so those leukemias cells are sort of like the weeds in the bone marrow garden that are preventing the healthy tissues from growing in the way that you'd want. I love that. It lets me use a quote I rarely get to, "Life's a Garden Man Digging." Last like movie, "Jodar." That's a really good amount. I really like that. All right. You want to take us through some of these particular subtypes of leukemias. We'll start diving in a little bit more into the weeds on these. Yeah. Yeah. So if we're thinking about myeloid leukemias first, leukemias broadly come in either acute or chronic flavors, but in the myeloid leukemia lineage, it's often either chromosomal abnormalities or somatic gene mutations are a combination of the two that leads to loss of cell cycle regulatory control where you have this abnormal proliferation of a certain cell or a malignant clone that could either be a single mutational event that's driving that process or over time a number of things in the machinery go wrong where you really lose those checks and balances and leads to a malignant clone proliferating out of control in a way that's disruptive to the bone marrow environment. And in myeloid leukemias, we'll see a crowding of the bone marrow, those weeds infiltrating the garden that leads to a decreased number of normal myeloid cells. And that can either manifest as pancitopenia as we've talked about where you really see low counts across the board or you can have a high white blood cell count. You see a high number of those myeloid cells in potentially low numbers of platelets and red blood cells, but the high white cells that are being reflected are that malignant clone that's really ultimately not functional in a healthy way. It's not that those white cells are good at fighting off infection, but we do see it reflected as leukocytosis with a high number of those leukemia cells, a good number of time in these cases. And so, actually, before you go further, can you give us a little bit of gestalt just from like when we're keep talking about people who come in, you get this initial blood test and you're looking at a complete blood count. In terms of that actual leukocytosis, what kind of numbers are we talking about here? Just to give it a listener is a little bit of perspective about, are we talking 20,000, 30,000 higher up and more potentially or just kind of some gestalt from your experience? It can be incredibly variable, but certainly all of those are within around a possibility where you see in the tens or even hundreds of thousands in terms of leukocytosis with acute myeloid leukemia. It's going to be a bit more of a range where it can be anywhere from pancidopenic where it's low close to zero versus 10,000, 100,000 or higher. In the chronic myeloid leukemias, leukocytosis is much more common and the numbers can be impressively high because it's often a more indolent course. It's been brewing for longer. Those cells are rapidly dividing and proliferating, but not in a way that causes more imminent catastrophic damage in a way that acute leukemia does. These patients come in with 50, 100, 200, 300,000 on their CBCs and it's not the calculus that's different as we'll get into for an acute versus a chronic. Certainly, you will see these impressively high white blood cell counts and it doesn't necessarily correlate with exactly the person that you're seeing in front of you. You can have an impressive CBC in a patient that's doing relatively well and vice versa. Putting the whole picture together is also incredibly important rather than just what the numbers are in the chart. I appreciate that. When patients have bad facial infection in the white blood, counts to sell count of over 20, I tend to get pretty concerned. If they came in with 100,000 plus, I think I would be quite scared. Seeing over 100K would be pretty wild and concerned. As we'll talk about with these conditions, especially for acute myelotomychemia, it's often the blast count that we care about more than the actual total white blood cell count. Drew, thinking about moving into talking about acute myeloginous leukemia or AML, would you want to start us off with talking a little bit about some of the epidemiology and other characteristics of the disease that we might be thinking about? Well, it's definitely the first one we're talking about here, acute myeloginous leukemia or AML. It accounts for over 80% of acute leukemia in adults. This is the adult one versus ALL, which we'll talk about next. It tends to be a little bit more common in men than women, but here we have an increase in the number of immature myeloid cells in the bone marrow, the blasts, like we talked about, leading to that bone marrow failure progression. The signs and symptoms are a lot of stuff that I've talked about, but here with the acute, it tends to be a more rapid onset of symptoms, right? The fatigue, the unexplained weight loss, maybe anorexia, fever, infections. You might get that strawberry red ginger-videosecordery to leukemic infiltration or new coastal bleeding. And as the bone marrow acutely gets compromised and we see that pan cytokina, we may see coagulation issues as well as even developing the serious condition of DIC, disseminated intracurricular coagulation. A very difficult thing to treat. We have a special term in here called leukostasis, a potential complication at presentation that is an oncologic emergency. Max, I was hoping you could walk us through this because at least an understanding of what this is, I think, is important. Absolutely. And this is why when somebody with AML is coming into the emergency department or clinic, what we really want to look at is not just the white blood cell count, but the blast count, those immature cells, because leukostasis is a life-threatening condition that's really driven by how many blasts are moving through their circulation. So thinking about blasts as the big, ugly, sticky, incredibly immature, white leukemic cells, these are the cells that moving through circulation, if there's enough of them, can get stuck in capillaries and essentially cause tissue ischemia. And so most often what we see in leukostasis is that it manifests as shortness of breath because of pulmonary involvement, where people can be confused or have stroke-like symptoms because of brain involvement, but other end organs can be affected by leukostasis as well. And this is a condition that really is an emergency and requires emergent management. And we often try to preempt the development of leukostasis in high-risk patients to prevent it from happening. Because once leukostasis develops, the morbidity and mortality that are associated with it is incredibly high. And so what we can do when somebody first hits the emergency department and they're at high risk for leukostasis, we can bring down the white blood cell count with a couple of measures. In order to temporize the white blood cell count, we can use something called oral hydroxyurea, which inhibits DNA synthesis and it really is good at impacting cells that are rapidly dividing. So these leukemia cells, especially acute leukemia cells, are impacted first and pretty quickly. And then we can also flood people with fluids. And so hydroxyurea plus fluids is a way to at least temporize these patients to get the white count down while we're working on getting them admitted to the oncology unit and started on more definitive therapy. But we have other interventions, specifically bucapheresis that can be used to rapidly treat the blast count if needed. And so there are certain measures that we would take. You know, if somebody has symptoms, that's an easy indication to take them for leukapheresis, which involves the placement of a pharesis catheter, which is a large catheter that's going to be placed in the IJ and is typically an indication for admission to the ICU while you can perform this and get the white count down. But if somebody comes in and has a blast count, typically we use 50,000 as sort of a cutoff. So if somebody had a white blood cell count of 100,000, but it was 50% blasts, so their blast count is 50,000, that even without symptoms places them at substantially high risk of the development of leukostasis, which we want to get ahead of. And so it's often a judgment call. You put together the complete picture of what's going on with the patient, but certainly that could be an indication for placing a line and getting started with leukapheresis right away to prevent this condition from evolving. And so we like to be aggressive. And one thing I think is super important is that the first CBC matters, but it's the second CBC six hours later that tells you how fast this condition is moving. So everybody's disease biology is going to be slightly different, but you can get a sense of the doubling time when you have serial pieces of data, where if the first blast count is 10,000 and they're asymptomatic and you're overall reassured, wait until we get the second in the third CBC to know how quickly their leukemia is moving, because this condition can get away from you quite quickly. And so you really need to know the tempo of disease so that if somebody's in the emergency department overnight waiting to be admitted, it doesn't become an evolving issue that you're behind on is something that I think is really important for these patients. I was not even super familiar with this potentially life threatening complication that can develop. So having some awareness of it I think is important, but very cool and thanks for laying out kind of how you work through it and manage it. Let's move on to how we treat AML here. Before we get into this, I think in Max is somebody who's more familiar in this world, the guidelines and evolving nature of the treatment for these disease states and hematologic illnesses, changes a lot, it's a lot of moving targets in guidelines. So what we're talking about currently might not be what's done a year from now, although probably close to it. But can you kind of take us through how you think about treatment and what we are generally done for starting off with this condition for AML? Yes, it's a really great point. Across oncology, the field is moving so rapidly. It can be difficult to keep up with the guidelines in any individual disease space. And as our efforts in precision oncology become more and more refined, all of these diseases are becoming sub-typed based on mutation status, biomarker status, we have targeted therapies. And so for a lot of these, we'll be talking broad strokes as a way to think about general treatment paradigms, what is the more broad standard of care and how we approach the management of these patients. But like you were saying, Drew, things change a lot and fairly rapidly and there's a lot of nuance here, which it's somewhat difficult to talk about specifics, but also very exciting. Because I think we're constantly seeing the emergence of new precision directed therapies that can help improve outcomes for these patients. But for AML specifically, really broad strokes, we think about two phases of treatment. We have induction, which is the idea of inducing a remission. You want to put the leukemia into remission and then a consolidation where you consolidate that remission to hopefully keep that leukemia in remission and effectively cure the patient. And if you see somebody with new AML, there are several major branch points in that decision in terms of what treatment they're going to get and with what intent. But two of the major decisions right off the bat are one to determine the patient's fitness for transplant. And when I say transplant here, I'm talking about allogeneic stem cell transplant, a transplant from somebody else, as opposed to an auto transplant, which is something we'll talk about a little bit later. But for AML patients would get an allo transplant. And then two is to determine their risk. What is the risk of the disease and how are we thinking about that individual patient risk? And for transplant eligibility, this has evolved over time, especially as we get better at managing the complications of transplant. We have a lot of emerging therapies and interventions to help transplant be less of a morbid intervention because it's an incredibly powerful therapy, but comes with a lot of risk associated with it as well. And so we often think about patients being under 75 years old, it can be center specific, but that generally is an age cut off that most guidelines use and fit enough to tolerate a transplant. I mean, by fit, I mean, the end organ function, the heart belongs, the kidneys are all adequate. And they have a good performance status as well. They're able to be up and out of bed or walking around as long as it's not necessarily all attributable to their leukemia. But their baseline form and status prior to developing leukemia was adequate to be able to tolerate undergoing this procedure. If a patient is not fit for these type of more intensive interventions, there might be an upfront conversation of whether or not treatment should be started with alliative rather than curative intent. The idea being we can give you treatments for the leukemia to help you live longer and help control the disease, but it wouldn't be with the intent of curing the leukemia, which for a majority of patients requires a transplant for AML. So once we determine their transplant fitness, we also want to determine their disease risk. And it's broken down often into three categories of favorable, intermediate or unfavorable disease. And there are factors that come into this assessment, essentially looking at the cytogenetics of the disease and the mutation status. And largely, these biologic factors of the leukemia can help us stratify patients by how sensitive their disease is to chemotherapy, which is often how I think about this risk stratification, where more favorable disease is going to be more highly sensitive to chemotherapy and more unfavorable disease is going to be less sensitive to chemotherapy. Because the patients with favorable AML are people that you can potentially cure with just chemotherapy alone. That you don't necessarily need to take the transplant. People with intermediate risk disease are unfavorable disease while you can put them into a remission with chemotherapy. We know that the natural history of the disease will say that the chemotherapy will come back eventually if you don't take them to transplant. And so people with favorable risk, there are certain classic alterations that are associated with this. There's a translocation of 821. There's an inversion in chromosome 16. And I think about these alterations as there's a single driving alteration that really is responsible for the development of this leukemia. Giving them chemotherapy is potentially enough to cure that disease as a way to wipe out that leukemic clone. And then maintain them in remission without taking them to transplant. As opposed to people with unfavorable risk disease, these are often people with more complex carry types. There are lots of different mutations or there are certain mutations that we know predict less sensitivity to chemotherapy where we really need that powerful, allergenic stem cell transplant and the transplant versus leukemia effect that comes with it in order to keep these people in remission and give them a chance or cure. And that helps us determine and someone tolerate a transplant and what is the risk of their disease in terms of what are the optimal therapies to give them. For this curative intent treatment, we think about that induction with chemotherapy, the induction phase, as often a combination. Classically, what we use is something called seven and three, which is two chemotherapy drugs. Donna Rubison, which is an anthracyclean chemotherapy and an antimutabelet called cyterobene that are given together. And you give these agents together during that induction phase to induce a remission to put that leukemia into remission before you move to a consolidation. Another option that's emerged as a standard of care and has really revolutionized the treatment of AML is using a combination of a hypomethylating agent, either azocytidine or cytobene combined with something called venetoclax, which is a BCL-2 inhibitor. And this is a great regimen, especially for older patients or those with unfavorable risk disease or antecedent myelodysplastic syndrome, because it can be easier to tolerate than seven and three. And those patients with the unfavorable risk disease, especially if they've had myelodysplastic syndrome that has evolved to leukemia, which typically is associated with a more heavy burden of complex cytogenetics, various mutational abnormalities, potentially not as chemotherapy sensitive, that using these more targeted agents of a hypomethylating agent with venetoclax can potentially improve the outcomes that we see of getting them into that remission. If a patient fails one, sometimes we switch to the other. So if we try to get a remission with seven and three and they fail, often we can switch to HMA venetoclax to see if we're able to induce that remission before, say, taking somebody to transplant. But that is the next phase. After we go through the induction phase, we'll repeat a bone marrow biopsy, we'll look at the bone marrow, we'll confirm, okay, their leukemia is in remission. We have a window to consolidate that remission and in many cases that is moving forward with alginate, stem cell transplant or in the case of people with favorable risk disease, you can give them several rounds of chemotherapy alone, which can be curative for those patients. If on the course of giving them chemotherapy, they have evidence of relapse disease, those are patients that eventually you can also potentially take the transplant. And the process of going through alginate, stem cell transplant is in itself complicated where you go through HLA typing, make sure that you have a match or a mismatched donor, conditioning for transplant and then the post transplant course. So that I think is a discussion and a topic a little bit all unto itself, but just know that the majority of patients to be cured from AML require a transplant eventually, but the first step is to go through induction, get them into a remission before you take them to transplant. And there is this subtype of favorable risk disease that can be cured with chemotherapy alone. If a patient is transplanting, and eligible, say we have somebody that comes in, maybe they're a little older, 80 years old, slightly frail, has some questionable end organ function, then we would proceed with palliative intent treatment. The standard of care at this point, if somebody can tolerate it, is to also give them the hypomethylating agent with venetacrax, assuming that they're able to take that, but you can just continue that indefinitely as long as it's working to control the disease. And I think for a lot of patients, this has also revolutionized the management of acute leukemia, where there wasn't a ton of great options before this. I mean, HMA venetacrax is also has the overall benefit is I wish it was better. The overall survival in the studies was looking at something on the order of about 15 months, but compared to before the approval of decided being or as decided being with venetacrax, these patients would live closer on the order of months. And so being able to help people live longer, control their symptom burden, and allow us to control their disease, even if we know it will be for a limited amount of time, has been really helpful for a large portion of the population that might be older or more frail that are nearly diagnosed with AM out. Let me give you some thoughts that are percolating through my mind, then brain as well. For a saw, I love listening to talks, that's so eloquent, and it's so helpful, I think, for to hear from you about how you need to think about the treatment phases for these patients, especially if we're going to be asked to potentially intervene with some sort of moral surgery process around these and talking to the treating oncologist and trying to figure out best and most advantageous window to do whatever we have to do. You know, generally we're not talking elective stuff here. It's more than that urgent semi-urgent category of dealing with infected teeth or dealing with some sort of issue. There's definitely some sort of a star wars joke in there, I was trying to think, but the Clone Wars are prevention of the clones here with all the movie Clone cells, which I love that I'll pass that along. In terms of the various chemotherapeutic agents, and I appreciate it, certainly helpful, and we're doing this on purpose to lay out the current standard of care, with the evolving nature and there being so many. It's super important, if our patients have had or are on chemotherapy, to not only really look those medications up and understand what they do, but then discuss with the oncologist about the effects around surgery. The other thing that I'm sitting here thinking about is the way that I like to conceptualize medicine as if you're a listener of this podcast is you have to understand the pathophysiology and what's going on, and then it's about risk stratification, right? And listening to UMACS layout, trying to determine the risk stratification and eligibility, it's a beautiful microcosm, I think, of that. Just like our last episode, talking about risk stratification with anti-collegulation are procedures. Very kind of similar thing. It's all about understanding risk, communicating it between the doctors, and then figuring out what we're going to do for these patients at what time. Great. Any thoughts on that? And kind of that general, how people are treated for most of these diseases? No, that's a good run through. One question I had was, think ML's more common in adults who are saying in males. Is it more common in younger males? What is the age that I usually see it in? Often, they're can be age-range, but we see it often in our older population, especially as contrasted to something like ALL, which is more common in our pediatric population. And anecdotally, I don't know the data on this, but I've seen a lot of, if we do have younger patients with ML, they will often have more of that favorable risk disease where they have kind of this canonical 821 translocation or an inversion 16 that we know that that alone is enough to drive the development of AML, subsequently also making it very chemotherapy sensitive. If we have somebody that has AML that has complex cytogenetics, multiple mutations, or especially if they had MDS, myelodispastic syndrome, which we know is related to age that then developed into AML, these are things that develop over time, over decades of life. You have a few alterations or changes that accumulate, and eventually people develop AML, and they have several things that have gone wrong before that leukemia actually developed, which tends to be people in their fifth, sixth, seventh decade of life, and also makes the disease a little bit more difficult to treat with just chemotherapy alone, because there's several of these checks and balances in the cell cycle regulatory control that have gone wrong leading to the disease. That's often those are the patients that we really need to transplant to cure. The idea with the transplant is that you take somebody in, you give them conditioning chemotherapy, you wipe out their bone marrow, and then you give them stem cells from a donor. That donor stem cells then take residents in a bone marrow and start to proliferate, and so you have somebody else's stem cells that are growing as a way to repopulate the bone marrow. We know that just giving a whopping dose of chemotherapy alone isn't enough, especially for these chemo-resistant leukemia clones, to eradicate the disease forever. We have some malignant clones that are hiding out and maybe protected areas within these bone marrow spaces that the natural history would be for it to come back. It's really the immune effect of the transplant. We call it the graft versus leukemia effect. It needs to be a transplant from somebody else, and then their immune cells from that transplanted patient will ideally hunt down and kill any remaining leukemia clones that are hiding out, say in some of those more protected spaces. On the very same knife's edge, you also have something called graft versus host disease. You want the transplant to kill the leukemia, that's, say, leftover, but you also want to minimize the amount of damage that the transplant is doing to your other native tissues. We often see this manifested as rashes in the skin, where it's attacking the skin, diarrhea, where it's attacking the gut, or trouble with the liver, where it's attacking the liver. We have more and more strategies of immunosuppression or other ways to mitigate the risk of graft versus host disease, but that's largely what a lot of the morbidity and potentially mortality associated with transplant comes from is you want this double-edged sword of graft versus leukemia while minimizing graft versus host. But it's not necessarily the overwhelming amount of chemo that you gave and then gave them a transplant, it's the transplant itself that's doing the curative treatment. That's a nuance with allogeneic transplant. As opposed to auto transplant, auto transplant, you're giving somebody their own cells. The treatment that you're really giving is a whopping dose of chemotherapy. You're giving so much chemo that somebody would die unless you gave them a rescue. So it's high-dose chemotherapy with a talligous stem cell rescue. It's really the kind of full-pidle of that intervention. You give them a super therapeutic dose of chemo and then you give them their own cells back. The goal of intervention between an auto and an aloe are slightly different in those respects. As we progress forward here, there's a little subtype I just want to mention briefly. Similar to AML, I want to talk about APL, acute pro-mylocytic leukemia. Not as much thought about, but it's a subtype of AML, but it has a little bit of distinct biology and a good prognosis to be aware of. Typically results from a translocation of chromosomes 15 and 17. What happens is this blocks differentiation of pro-mylocytes into mature granulocytes, driving disease. You get some particular things on a smear, including blasts and atypical pro-mylocytes plus hour rods, AUER. That's kind of a buzzword that some of you folks might remember from studying for the CBSE or various things or step one or two, but those are needle-shaped inclusions. The thing you remember is with this, you especially have a very high risk of DIC and bleeding in APL, so these patients often require quick treatment and especially if they have DIC. Management, we try to do an early treatment pretty aggressive because they can have high mortality, secondary to equi-galopathy that can develop. But if they're treated on time with some of the current agents, then the long-term outcomes are pretty good. Anything else you want to just add about APL max before we kind of keep sliding forward? It's often one of those leukemias that we think of as an emergency. They need emergent treatment. You need to give them all trans retinoic acid or atra early, which overcomes that differentiation block and allows them to start moving the cells through differentiation to, as you had said, treat or prevent some of that quad-galopathy concern. Once you get these folks on treatment, they have great outcomes. As soon as they hit the ED, it's kind of like we need to intervene early and we know that they're going to do pretty well as long as we can get them through the first few days or first week or so. When somebody comes in with acute leukemia not otherwise specified, before we have more specific information about what subtype it is, sometimes we will just give these patients atra, at least a dose, until we know that it is or is not APL because the risk of harm is quite low and the potential benefit is quite high. If there's any question, we'll just give it and then figure it out later. Let's look at the other side of that coin and let's look at chronic myeloginous leukemia or CMS max. Can you kind of take us through that, you know, chronic versus the acute one we just talked about? Yes. I know another leukemia in the myeloid lineage, but this is classically associated with the Philadelphia chromosome. What you really see is an increase in more mature myeloid cells throughout the peripheral blood and the bone marrow, not fully mature, but certainly not the predominance of blasts that you would see in an acute leukemia. And the Philadelphia chromosome, which that term might be familiar to some people, is a translocation between the BCR gene on chromosome 22 and the able gene on chromosome 9. So it forms BCR able and we know that that fusion is what really drives the disease and also has opened up what has been revolutionary in terms of the management of this condition and really an incredible blueprint for precision oncology across different cancer types. And so it's not something that's hereditary. This is generally a spontaneous, somatic mutation that occurs in people. So we see it rarely in younger patients and it's more common in our older patients in the fifth or sixth decade of life and it's also more common in men compared to women. And I think about CML is like we talked about the acute versus chronic, some more indolent course frequently discovered incidentally on a blood draw similar presenting symptoms as we kind of talked about, but here with the chronic I'm thinking, hey, that white blood cell count could be over 50,000, 100,000, 200,000 with myloid cells and all stages of development, that mylocyte bulls and presumptively this diagnosis can often be made on a differential and blood smear. Can you kind of talk to us about the phases of CML max? I think having some understanding this is important. Yes. Just to expand really quickly, really quickly on your last point, you can before just on looking at the CBC, you can often make a presumptive or you can really tell a diagnosis of CML just on the differential, which is kind of neat. You have a patient that comes in the ED with a white blood cell count of 100,000. So red flags are already up. What's going on with this patient, if you saw that 50% of those were blasts that would have me running to look at the smear, I'm worried about a leukemia and all the things that come with it. If you have a few percentage of blasts, but you have a predominance of slightly more mature cells, you have a high increase in the mylocytes, the metamilocytes, especially if you have an abnormal level of basophils and eocinophils. That is a very classic CML differential. They call it the mylocyte bulge because you see this increase in the percentage of mylocytes which are sort of, as we were talking about earlier, with the pluripotent stem cell that differentiates to the common progenitor that then differentiates these more mature cells. We're not at the blast phase up at the top, but where there's issues sort of further down in this differentiation process. You can see that represented on the CBC. At least if you're sometimes we get paged about these patients overnight, it makes me feel at least slightly more reassured in terms of the urgency with which we need to intervene. If we see that classic CML differential in somebody coming in with a newly quite elevated white blood cell cat. Since we do make the diagnosis, which we really want that BCR able fusion, the Philadelphia chromosome, that's based on blood PCR or from bone marrow studies that helps us cinch the diagnosis beyond the presumptive diagnosis from the diff. Once we know that the patient has CML, there are several phases that we think about which helps us determine management, treatment, and that's the chronic phase, accelerated phase or blast phase. The chronic phase is the most common presenting phase that we see people in and the absolute level of circulating blast in the chronic phase is pretty low. There's usually some, sometimes no circulating blasts, but chronic phase CML can be further broken down into low, intermediate or high risk. That's most commonly based on something called the circle score, although there are a couple of different scores that can be used and it incorporates things like the patient's age, how big is their spleen, what their platelet count, and what is the percentage of myloblast that you can detect circulating in the periphery to help determine are they low, intermediate, or high risk. There's also accelerated phase CML where you see the peripheral blasts being closer to 15 to 30% in the periphery and then there's blast phase CML where the blasts are over 30% in the periphery and those are patients where even though technically they have CML, you're really treating them like an acute leukemia because that blast percentage is so high we see that it can have the aggressive characteristics and biology more associated with an acute leukemia and those patients require different treatment paradigm. But for lots of patients, for the treatment of CML in chronic phase, we think about treatment with agents that are tyrosine kinase inhibitors or TKI's and those are medicines that target the Philadelphia chromosome and these agents in CML really revolutionized precision oncology and now we have lots of TKI's that have different targets in various precision oncologic therapeutics that are more focused on specific mutations or alterations or biomarkers that we know that we can detect on certain diseases but CML is an incredible example of identifying a driving mutation and developing a drug against that mutation that has allowed patients to live longer, treat their disease and really completely change their outcomes. And so the first generation TKI's for CML is something called a matnib or Gleevec which people may have heard of but over the years there have been other generations of these agents developed that may be more specific or have different side effect profiles that we have incorporated into practice and some of them are drugs like distatinib, nalotnib or bosutinib and if somebody has chronic phase CML, if they're either chronic phase intermediate or high risk then we tend to favor using a second generation agent over a matnib. If they have low risk chronic phase CML then the outcomes tend to be fairly similar and so we could go with either an earlier generation or a later generation agent but the selection of the drug often comes down to individual patients because they have while similar outcomes they have distinct side effect profiles and so that can help guide some of the selection of the drugs that we're using. So for example in the lotnib we know can drive atherosclerosis, predispose people to the development of type 2 diabetes and so there are certain populations of patients that we maybe don't want to reach for that in and then distatinib, sometimes we call it distatinib to remember that it can drive pulmonary hypertension or plural effusions thinking about a patient population where maybe that might not be the best option. But once we get a patient on a TKI it's really an oral therapy that you take once a day at home it's not intravenous, people often do quite well on these medicines and we monitor the CBC. First we want to see can we get a hematologic remission? Does their CBC specifically their white blood cell count normalize? First we want to look for a molecular remission. We're looking for that BCR able fusion protein in the blood and checking it on PCR and we want to see it decrease over time to nearing undetectable levels. CML has become this condition that's very treatable, people do quite well on it and there is a portion of this population where after several years on therapy if the BCR able becomes undetectable you can actually stop treatment and then about half of people will functionally be cured and you can keep them off of therapy and just on observation only. Other people you'll start to see the clone come back once you stop the drug and then you need to restart the therapy. But just a really great example of precision oncology and targeted therapies understanding the biology of the disease. It's super cool that you can use PCR tracking, the BCR able fusion levels in the blood to look at treatment. It's just awesome. The precision oncology stuff that's been all the thing that you're in your world is just incredible man. Another point as you're going through the chemotherapeutics particularly with something like the satinib, it's one of those ones I file away in my oral surgeon brain to be like okay we have a lot of potential lung complications right? I might want to be really careful or not use nitrous oxide. I also think of bleomysin in that camp and there's so many chemotherapeutics that you're not going to remember these but a lot of times the secondary implications of somebody who's had these medications are what we need to think through before doing treatment of some kind right either an IV sedation or nitrous oxide or something so we're understanding the other organ system effects of it. So that's another like getting the chemotherapeutic regimen and talking to young colleges I think is super important about those agents specifically. I did want to mention two max because you're talking about the targeted tyrosine kinase inhibitors for those of you folks who've read the you know last amus update on emorons right there is that blurb category of older similar medications right? I you know I'm not even super deep though the particular evidence for some of the less common agents but I had a case that it was hard to tell if it was either you know just osteomyelitis or osteomyelitis secondary to a tyrosine kinase inhibitor and more of an emoron picture you know chicken or the egg that we ended up having to resex them these manable and so remember too that some of these newer development chemotherapeutics and issues would probably going to see manifesting and having more clinical data to support emoronge you know over the next five or ten years. I kind of think it's tyrosine kinase receptors of does it cause emoronge? I don't know maybe but it probably has the potential to the some degree even if it's rare. What do you think Grant? Yeah I think that's good to have on your radar I like that you mentioned how it can affect some of the things you're doing in oral surgery with our sedation and nitrous and other things like that. One question with when we were talking about the AML I mean how often is this diagnosed in the dental chair you know does that happen or like you know people open their mouth and you see stuff going on flame gingiva or is that like farther down the line and you kind of already know they have it. Because I was actually thinking about that same thing Grant and I've never primarily diagnosed like one of those conditions. I feel like it's one that you know your friends or friends kids that you get asked a lot like oh my you know my kids gums are a little red I'm worried they have them keeming or like it's not leukemia like you know I have them lost but I'm not sure like Max have you ever like looked at somebody's oral cavity or seeing some of this you know we call it that strawberry red because there tends to be stippling and just easily bleeding. I don't know if you've ever seen that you're obviously seeing you know potentially a lot more in these patients than we are it's pretty rare for us to especially in the undiagnosed or acute phase come across somebody like this. Yeah I think often these are patients that I'm seeing being admitted to the service they've come to the emergency department and so I'm not sure how frequent it is to sort of discover more in the community and then get referred in from that perspective but I feel like it's fairly infrequent. I think most of the people will either have some other type of symptomatic concern or what we see not infrequently is oh I was feeling well I went to my primary care provider I got blood work and my CBC looked really bad and they sent me in and so that's a also a common story that we get. I do think about it certainly on you know you get pathology, Val or you know you have the kind of oral presentation and then you start asking those questions about symptoms night sweats, unexplained weight loss. The lot of that stuff starts to add up and I start to get real concerned for any type of malignancy but I certainly think it's something to keep in your thinking about these things as you look at your stuff in the mouth or particularly with bleeding or that you know striber edge injury because you know if you manage to catch it you may save somebody's life for this kind of stuff so good let's move through now and look at the other side for ALL or acute lymphocytic leukemia and this is the malignancy kind of characterized by proliferation of immature lymphoid cells in the bone marrow, peripheral blood or other organs and so with lymphocytic leukemia these can be B cells, T cells or natural killer cell these neoplasms but about 85% of them are B cell related. Natural killer cell are the least common type and T cell is more common in adolescents and the rare natural killer cells a little bit more common in adults but generally like Maxisaki, we have those clones or malignin clonal proliferation of lymphoid stem cells and this is what we think about the most common childhood leukemia right and I can't say about two thirds of childhood leukemia and only about 20% of adult similar signs and symptoms you know I'm not going to go through it again but that we talked about but here we also get lymphednopathy right, extra-nodal involvement of the CNS testes, liver and spleen and oral surgery related we can have that entity known as numb chin syndrome right where we get sensory neuropathy and numbness involving the distribution of a mental nerve which can be a wound presenting symptoms so you know patients showing up with weird parastegias or anesthesias that haven't had surgery you know this could be something that's you know going on with them Max can you kind of talk to us a little about the cytogenetics of this? Yes I think in terms of the cytogenetics it one big branch point that we've seen evolving in ALL that's important to look for at the very start of anybody with a new diagnosis is this Philadelphia chromosome negative versus Philadelphia chromosome positive as we had talked about the same rearrangement with CML where it changes our therapeutic options and how we approach the disease and prior to the development of these tyrosine kinase inhibitors Philadelphia chromosome positive ALL was associated with worse outcomes but now that we have these targeted therapeutics it's actually flipped and so we can utilize these precision oncologic agents to change patients' courses and outcomes and so understanding Philadelphia chromosome positive versus negative is important upfront and there are many other cytogenetic or mutational changes that are you can be seen in ALL but I think that that's a big one that has therapeutic implications right off of that. Max I just want to highlight because a lot of the you know we think about like or you know in test questions if you get a test question on like CML often you have to identify the Philadelphia chromosome right the translocation you know BCR able but you can have Philadelphia chromosome will abnormalities and something like ALL is right is that's that's kind of what you're saying. Yes and it changes treatment awesome. Can you take us through some of those treatment thoughts? Yeah absolutely so ALL in general is a leukemia that we're thinking about as being generally pretty responsive to chemotherapy and and one that we're trying to cure with chemotherapy especially in that pediatric or young adult population and so childhood ALL cure rates can be in the 80 plus percent range as you move into adolescent young adults people that are 18 to 40 cure rates a little lower maybe 60 to 80 percent and then as people get older they tend to have less favorable outcomes and that may be related to a number of factors but including the chemotherapy regimens that we're able to give or that patients are able to tolerate where younger people healthier more fit tend to be able to tolerate either higher doses or multi chemotherapy regimens a little bit better from a side effect and morbidity standpoint but with ALL as with other leukemias we think about different phases of treatment where we have also an induction phase where we want to induce a remission using chemotherapy we have a consolidation phase where we want to consolidate that remission and then a maintenance phase where we want to maintain that remission with the drugs that we're giving and this can be with chemotherapy or as we talked about with other agents being used such as the tiresome kinase inhibitors for patients that have Philadelphia chromosome positive ALL the combination chemotherapy that is used in ALL is very complicated and there are many different approved regimens that can be used and it also is dependent on the age of the patient in terms of what regimen or inspire regimen might be employed in practice there are several main classes of chemotherapy that are used in these in these folks or younger either pediatric or adolescent young adult patients that can tolerate it a sparigenase is used in older populations this is an agent that while very effective in treating ALL often has to be not used because of potential side effects and morbidity associated with it including the risk of things like bleeding into the brain in addition to a sparigenase anthracycines are used been christen which is a microtubule inhibitor anti-mitabula chemotherapies like cytarabine an alkylating agent like cyclophosphamide as well as steroids in lymphoid leukemias steroids actually have an anti-neoplastic effect they impact the immune system they tamper things down so it's part of all of these chemotherapy regimens that steroids will also be built into the treatment strategy but these multi chemo regimens can be employed that again depend on the patient age in terms of which ones you're giving and then they have different phases that they're given in induction consolidation or maintenance ALL also has a very high risk for CNS involvement and so it's important that any patient with ALL has a CNS directed therapy plan often that's with methotrexate that you can give interethically or high dose methotrexate has the ability to cross the blood-brain barrier for treatment of the CNS but if a patient is in that young adult population the classic regimen that we think about using is something called CalGB10403 that does involve the use of a sparigenase amongst these other chemo agents and can have these good curates or patients that can handle it but as we get into an older or more frail population there are many other regimens that there's no one substantially better regimen but something like hypercyvad is one that we'll often see which is the pscyterobene v isvinchristin a is adriamisin or an anthrocycline chemotherapy and d is the dexamethasone which is the steroid that we see built into these regimens but there are several different regimens that are approved which might be chosen based on patient specific characteristics or institutional preference and then for BCR able positive disease these tyrosine kinase inhibitors are being moved into the forefront of treatment so either they can be combined with chemotherapy or we're starting to see actually chemotherapy free treatment strategies for these patients so you can use a tyrosine kinase inhibitor combined with steroids to induce a remission followed by treatment with something called blinatumamab which is a bite or a bi-specific T-cellingager which is a really I think neat next generation drug design that binds antigen on the leukemic B cell in the case of blinatumamab CD19 and then it also binds CD3 on T cells so you have these leukemia cells that it binds to and then it also binds to your immune T cells and brings them close together bringing the T cells to the ALL you can directly mediate T cell mediated cytotoxicity and lead to cell killing and so that's been a fairly new development with these bites that are being used in leukemia things like ALL or multiple myeloma but this idea of having a chemotherapy free treatment strategy using just these tyrosine kinase inhibitors like melatonib or desatinib plus blinatumamab as a way for helping potentially cure patients that cannot tolerate chemotherapy has been a really big shift in our treatment of ALL especially in some of these older patients. Nice, that's incredible moving away to chemotherapy free regimens and it brings to mind a lot of the developments in melanoma treatment of unmasking the malignancy of the immune system to what it do what it does best and kind of kill it for ourselves and hopefully that you know we keep getting better and better at this to you know bring our immune systems into the game as well and more super cool man. So let's finish it off and hit the last one of the four here of the the major ones CLL chronic lymphocytic leukemia again a lympho proliferative disorder with proliferation and accumulation of mature appearing neoplastic B cells are lymphocytes within the bone marrow or other parts of our body and these immune and confident lymphocytes can't differentiate fully in the plasma cells. This CLL is overall the most common leukemia again most commonly adults over the age of 60 but here about 70% of patients are asymptomatic at the time of diagnosis so particularly caught on routine blood work so it very much as it tends to be an indolent disease process kind of painless slow kind of going with you know you can have those same things like constitutional symptoms and other things a lot of times you can get expression of B cell associated with antigens things like CD19 or 20 or 23 expression of CD5 and Max can you talk to us if I first of all I missed anything but just briefly about kind of the staging and prognosis of CLL the most common yes and so CLL generally has quite good prognosis it's as you mentioned very indolent often caught incidentally on routine blood work and for many patients doesn't require any treatment at all you can just watch it and that's in part due to the more indolent nature of these leukemia cells slowly growing slowly dividing and we also know that compared to something that's more rapidly dividing like an acute myeloid or lymphoid leukemia they're also going to be not responsive to traditional chemo therapies in the way that an acute leukemia would so it's both more indolent and often doesn't cause people to many troubles but is also not something that we have a standard curative regimen for where really we are treating as needed for patients that are either symptomatic or we predict will become symptomatic to prevent that from happening and it's often staged using something called the Rai staging system and that's just based on patients will have a lymphocytosis elevated number of these abnormal lymphoid cells that we see on the CBC and then with or without some other troubles going on so if the lymphocytosis is the only thing that we see then their Rai stage zero and these are patients that we can often just check a CBC every six months and keep an eye on and but we don't actually need to do anything because it's not going to cause them any troubles and they'll probably live the same number of years that they they would have otherwise but if they start to develop things like lymphatmopathy, spleen enlargement we start to think about okay maybe they're getting into this intermediate risk CLL and then if you start to see cytopenias low red blood cell count or low platelet count then that's telling me that the CLL is starting to cause troubles in the bone marrow with their healthy cells and these are patients that may either already be symptomatic say from Nenemia or have a higher chance of becoming symptomatic soon and so there's not really a great definitive way to say this person needs treatment this person doesn't it's really preventing those symptoms preventing the troubles that might come down the road for these for these folks what about when treatment is indicated max you know these are some chemotherapeutic agents that you know i try to think about the because they have ramifications in our potential work on these patients and some of the toxicity so i always particularly think about the BTK inhibitors i don't if you can expound upon that a little bit yes at the really great point especially when it comes to surgical intervention these are important drugs to know if your patient is on when treatment is indicated BTK inhibitors is first line approved interventions with or without anti-CD-20 monoclonal antibody so the first generation BTK inhibitor that you might have heard of or I've seen is called the brutinib but then now there are also newer generation BTK inhibitors a calibrutinib or zanna brutinib that are also approved and the important toxicities i think to know about these drugs number one is the bleed risk and BTK inhibitors increase the risk of bleeding by interfering with normal platelet adhesion and aggregation and it's important i think not only to know that these drugs can increase bleed risk but the platelet count in these patients can still be normal even though they have an increased risk for bleeding because of how it's impacting the adhesion and aggregation rather than the number of platelets that predisposes people to bleeding so a normal platelet count does not necessarily mean that the risk of bleed on a BTK inhibitor is mitigated and i think it's important to discuss what they're treating oncologists before any surgical interventions in terms of what would be an optimal time window for holding the drug to wash out before intervening and what's safe and often with these CLL patients again it's indolent it's slow growing many people don't require treatment at all being able to hold therapy for some amount of time prior to a surgical intervention is likely going to be okay so it just requires some close coordination and planning if somebody needs to be off their treatment for a period of time for a surgical procedure that's often not a big issue the other toxicity that these predispose for is cardiac arrhythmia things like a brute nibb can increase your risk for atrial fibrillation which is unfortunate that it also causes a high risk of bleeding because somebody's on a brute nibb and develops a fib whether or not to anti-quagulate that patient is a very difficult decision and so that's a nuanced I think often personalized discussion but those are the two big ones bleed risk and cardiac arrhythmias that we say you'd be required to use that on a mock case somewhere is a very hard one you know what are some of the risk you know calculations and you know somebody on a BTK inhibitor and a fib not I think that would be too me even for us fun that that sounds like a very cool little narrow thing there yeah I think most people would would not anti-quagulate I have seen it that nuanced discussion in several patients so we've kind of covered the major leukemias and I think what we'll do on the next episode is cover the other main group the lymphomas things like hodgekins or non-hodgekins especially stuff gosh I've had a couple of number of lymphomas that I've biopsyed in the last 12 months and had found in patients as well as things like multiple myeloma and similarly other kind of things that can happen any final thoughts on kind of the leukemias from either of you gentlemen this has been a fantastic review I really appreciate both of you guys running through some of the details of these various leukemias and treatments and we did probably get into the treatments a little more into the weeds and most of us will need but I think it's helpful to at least know that and be able to guide our patients and know what's going on with their medications when we see them listed on their charts and be able to talk a little more informed about you know their treatment methods so it's been fantastic I thought it was great yeah I think those keys are you know digging and getting that oncological consult because so many of these medications do have ramifications in either the sedation selection that we proceed with management of things like bleeding or you know during the episode you know if you're still here fantastic and you know props to you for digging deep in this but with the constantly evolving nature we at least need to you know try to stay up on things and communicate and look those things up because as you can see missing an understanding of some of these previous treatments and agents can really potentially have awful consequences on a patient something none of us want to do so do your diligence and communicate and talk to the oncologic team that's helping to take care of these patients that I assume you like that Max feel feel good from the surgeon side did not just cut things but actually reach out and talk about stuff but we we always like to hear and discuss our patients and make sure that we have an informed collaborative plan so it totally agree I think that having everybody on the care team on the same page moving plans forward is incredibly important well thank you to both of you as usual I'll put your contact information in the show notes for listeners we have further questions about the leukemias and look forward to part two of kind of the he-mong aspect of these the series thanks guys take care until next time team thank you thank you both great to see you yeah thank you so much for listening to this episode of everyday oral surgery more information on these podcasts please visit everyday oral surgery dot com I love feedback and would be very grateful if you would reach out to me via my email grants to kjmail.com and let me know what you thought of this episode or you can text me at 720441 6059 additionally if you have any topics you'd like to hear about or if you'd like to be a guest on the podcast please please email or text me I found many of my interviews through people who have been contacting me and have been listening and have gotten so many great ideas for more podcasts and that's what helps keep keep the podcast rolling so really appreciate making that extra effort and helping me out with feedback and knowing what to do next on the podcast thank you so much
PodcastTranscript AI