Welcome back to the Ninja Nerd Podcast. Today we have a new episode on Myelodysplastic syndrome, or we're just gonna go ahead and abbreviate that, MDS keep it quick and simple, right? I like it. Any way you can abbreviate something always makes my life, and I think a lot of people's life easier, but yeah. All right, so we'll keep it quick with that one. MDS, I don't know what that is. I think a lot of people probably haven't always heard of this one. It's kind of one of those insidious ones, something in older individuals, but. Oftentimes, it's kind of a common thing that may come up in the workup of anemia or sometimes pancytopenia. And so I think that's the big thing to take away from this is when a patient who's a little bit older comes in, they got either one or a couple different cell lines being affected. It could be a part of that differential. So I think we'll talk about that and kind of get a really good understanding at the end of this case. About how to really think about MDS. Alright, well as always, let's get right into it with a case. We'll go through some a patient case, some findings, and hopefully we can really learn a lot from this one. Yeah, I think we will. Alright, let's begin. We have a 70-year-old female presents with progressive fatigue, increased bruising, and mild exertional dyspnea for the past four months. The patient describes a gradual decline in her energy levels, forcing her to limit her usual walks around the neighborhood. Over the last two months, she has noticed easy bruising on her arms and legs without significant trauma. She denies chest pain, fevers, night sweats, or significant weight changes. She's experienced occasional headaches but attributes them to stress. There is no known family history of hematologic disease. She also notes that she has felt more prone to infections recently having had two sinus infections over the last three months, which is unusual for her. Her past medical history is pertinent for hypertension, osteoarthritis to the bilateral knees. No known malignancies, no prior radiation therapy or chemotherapy. She's currently taking amlodipine, acetaminophen as needed for her joint pain. Vitamin D supplementation. For her Review of systems, general fatigue, mild malaise. Cardiovascular, mild exertional dyspnea. No chest pain. Respiratory, no cough, no sputum production. Neurologic, occasional headaches, again, attributed possibly to stress. No paresthesias. Hematologic, easy bruising, possible increased infection frequency. Gastrointestinal, regular bowel movements, no abdominal pain. And then for her derm, no new rashes. Vitals, BP is 120/70. Heart rate is 90, temp 36.8 Celsius, and her O2 SAT is 98% on room air. Skin we note pale conjunctiva, scattered ecchymosis on her arms. Cardio she has a regular rate and rhythm. No murmurs, no significant jugular venous distension. Pulmonary is clear to auscultation. No crackles or wheezes. Abdomen is soft non-tender. No hepatosplenomegaly. Neuro- there are no focal deficits. Extremities, no edema. Full range of motion. Except for them knees, though. They Yeah, they'd be hurting. Yeah. Rice Krispies down there, but like potato chips, when you get out of bed, ka kaka based upon all this, we go back and say, all right, let's get a nice lab panel for her. Yeah. We order the following. We have a hemoglobin of 9.2, MCV of 105, white blood cell of 3,500, platelets 85,000. Reticulocyte count is 0.6%. B12 is 450. Folate is 9.0. We do an LDH, which comes back at 200 and a peripheral blood smear that we note for dysplastic neutrophils. I gave you a shat ton of information. Yeah. Are you able to process all of that? Yeah. I think the biggest thing is this patient. When you look at this, it screams pancytopenia just right off the chief complaint when you hear progressive fatigue, maybe even some palor, things like that, some exertional dyspnea. I. It's all signs of anemia, at least subjectively. I was able to confirm that based upon the CBC results, that gave me a hemoglobin of 9.2. So for this patient, hemoglobin boom, if it's less than, usually we say if it's less than 12 and a female, that's enough to say that it's likely anemia. This is 9.2, so I know that there's anemia. The next thing is I hear the bruising. A lot of bruising going on ecchymosis that's present on her physical exam. And then you get the platelet count and it's 85,000. So that's also low. Yeah. So there's another cell line that's affected. Remember I told you this is an old person disease, 70-year-old with potentially one or multiple cell lines. Anemia is the most common, but so far we got red cells and platelets. The third thing I heard is recurrent infections, cyop. Pulmonary infections are usually the common way. Sinus infections, pneumonia, bronchitis, things like that are pretty common. This is two of them over the past three months. So there's a recurrent infections that are coming about. Makes me concerned is there's something wrong with the white cell line. I. However, her white cell is low. Yeah. So wouldn't you expect it to be high with infections? It would as a response to an infection. But in this case, she's not developing a bone marrow that's capable of producing these white cells, and that's probably what's causing these recurrent infections. And so when I see that white cell count that is 3,500, is it on the, it's below the lower limit. So there is a mild leukopenia here too. I'd say the most significant ones are gonna be the red cells and then the platelets. So we do have a pancytopenia. Now, when you have pancytopenia, you always think what's going on with the bone marrow because it's always almost kinda tells you something's going on with the bone marrow. And so you probably remember back from like our normocytic anemia talk that we talked about, aplastic anemia where the bone marrow fails, like there's destruction of the hematopoietic stem cells and they just stop producing all cell lines. Well, MDS is kind of like that, but it's, you make this weird cell who then is not able to capably like- effectively produce all the other cells. So it's like this weird dysplastic cell and this dysplastic cell is not capable of making normal red cells, normal white cells and normal platelets, and it's very ineffective. So it's kind of like that. And so that's definitely concerning. So when I have this evidence of anemia, leukopenia, thrombocytopenia, and then the symptoms that suggest, that makes me definitely concerned for that. Now. There's a couple other things when we think about anemia for this patient. We see the MCV is high, so it's greater than a hundred. So that tells me it's macrocytic anemia. It's almost always, at least for your board's, B12 or folate deficiency, right? So one of the things you have to do is get a peripheral blood smear. And if you guys remember from that podcast, on macrocytic anemia, we check the peripheral blood smear. We look for hypersegmented neutrophils or not. Well, this found dysplastic neutrophils, not hypersegmented. So for therefore it's not gonna be a B12 or folate, but we still got the B12 and folate level and they were normal. Yeah. So it's not B12, it's not folate deficiency. And then the other thing is we got the reticulocyte count. And what we know about reticulocyte counts it is it tells us that the bone marrow is working or not. The lower the reticulocyte count is, the less likely that the bone marrow is actually producing these cells. And it's definitely on that lower limit of normal. So that makes me a little bit concerned that this bone marrow is really struggling. The last kind of giveaway here is when I see the Psudo-Pelger-Huet anomaly or neutrophils, which are these dysplastic neutrophils. If you see that, it's almost like. Pathognomonic for MDS the only way that we could really, truly kind of, kind of really get to the confirmation of this is we'd probably have to start taking a look deeper into the kind of the bone marrow and stuff. Yeah. Because right now a lot of things are screaming the peripheral stuff as a result of the bone marrow problem, but we gotta figure out what's going on inside of that bone marrow really well, Zach, that is a strong suspicion. What would be the next key diagnostic step here? So we gotta get in that bone marrow. So the bone marrow biopsy is gonna be the probably the best thing to do. So we will aspirate out the bone marrow because my kind of thing here is, I can't really 100% confirm that it's not like. Infiltration of the bone marrow from leukemia? I don't think it is.'cause I probably see different things on the peripheral smear. Yeah. I gotta make sure it's not aplastic anemia or something else. And so I gotta make sure that it's not like a leukemic infiltration. I gotta make sure that it's not aplastic anemia and then confirm my suspicion, which is MDS. So when I do that, what you'll see is you'll see the hypercellular marrow, for aplastic anemia, it's almost always hypocellular. It's filled with adipose tissue, so that rules out, aplastic anemia, if that's what it was. So I wanna see a lot of cells, but these cells gotta look super funky. They gotta be dysplastic appearing, and on top of that I'm gonna have some blasts. So you shouldn't have a ton blast cells. I want to have usually less than or equal to 20%. At least less than 20% blast cells inside of that bone marrow.'cause if it's more than or equal to 20%, that's acute myeloid leukemia. We're done. So I want to see some blasts, but not to the point where it's greater than or equal to 20%. So I wanna see weird dysplastic cells. I wanna see a really hypercellular marrow, and I wanna see, again, less than 20% of those blasts. And if I see that I'm pretty much, I'd say, confident that it's MDS, well, we do the biopsy. Okay. All right. And guess what? What? It shows hypercellular marrow, multiple dysplastic lineages and 5% myeloblasts. Yeah. So that's a, so that's a very confirming yeah, exactly. Well, then my next question is how do we stratify the risk and decide on treatment? That's a really important thing. So at this point, we've determined that it's MDS, but MDS can be one of those things that's a little bit tricky. So remember how I. And we kind of talked about if it was greater than or equal to 20% blast, it would be a AML. That's one of the big complications of MDS. How when a patient gets MDS, they're probably 70, 80 years of age, not trying to be mean, but your lifespan is a little shorter. The chances of a person developing acute myeloid leukemia from MDS, you're more likely to die from other things. Anemia, thrombocytopenia, recurrent infections before you actually develop. Probably most patients probably die before that, so they're not gonna transform in time. It's, yeah. So maybe 10% of them do, but most of them die from other related complications. But we gotta at least make sure that we determine which ones are higher risk. And then we can also use this to determine the prognosis for us, how to treat them. So we use revised international prognostic scoring system. But all you really know, need to know about this is you wanna know what is the percentage of blasts. That's the first thing that you need to know if it's really high. That's kind of getting you closer to the risk of a AML. The next thing is you need to know how severe is the cytopenias. This person's got all the cytopenias. All right? And then the next thing is you wanna know cytogenetics. There's one specific type of like abnormality within the chromosomes that can help us to have one drug that can target it. And so you always wanna check the cytogenetics and we're looking for specifically what's called a chromosome 5q locus deletion. And so that has a good prognosis and we actually have a drug that can target these kinds of patient populations to really figure out where they fit. That's what I would do that and kind of determine where they fall in that low intermediate, high risk MDS. Alright, well then, hey, we have some results for you. For you here then. Okay, so the patient has isolated 5q deletion on cytogenetics. Okay, that's good. And moderate anemia requiring transfusions every few weeks. What's the key treatment in it? So there is a drug that targets that. Exactly. So at this point, that's again, I told you the most common presentation is gonna be macrocytic anemia. And the problem with that is, is if they get low enough. You gotta give transfusions is sometimes you can actually check their EPO levels and look to see if their EPO levels are low.'cause that can't happen in this condition. So if their EPO levels get less than 500, you can give them like erythropoietin, which is like an ESA. But the best thing to do is if a patient's having transfusion dependency, there's a drug called lenalidomide. And it's actually able to really help with effective erythropoiesis, and so it helps them to make better red blood cells so that they don't have to have this constant need to get transfusions. So that's what I would do. First thing I would do, check the EPO, make sure it's not like less than 500 if it is. Start an ESA and try that for a little bit. But I would also be highly considering, especially since they have that 5q deletion, I'd probably start a drug like lenalidomide because that's actually gonna help to reduce the transfusion frequency, even despite me doing EPO. Well, lenalidomide is perfect for that 5q deletion. Yeah. What if she had a higher risk MDS? She has adverse cytogenetics or blasts creeping up toward that 10, maybe 15%. Yeah. So if she had cytopenias like this, blasts are getting higher and then she doesn't have that 5q deletion, then I can't use lenalidomide. Then we gotta use these drugs like hypomethylating agents, Azacitidine. That's probably gonna be the best one. Sometimes Decitabine can be used as well, but I haven't really seen that to be common. It's gonna be more the, as azacitidine. And that's been shown to potentially slow the progression of AML, maybe improve survival. And again, it can actually reduce transfusion dependency for these patients.'cause that's always the goal is to reduce the need for these patients having to go and get transfusions. Because imagine if you got a blood transfusion. Every so many weeks when you get blood, you get iron. When you get iron, you end up in increasing the risk of secondary hemochromatosis too. So that's another potential complication. And then you also run the risk of other things that can happen with repeated blood transfusions, as we talked about in the blood transfusion lecture. It's always a good idea to see if we could reduce that need and help them have a better quality of life. So Azacitidine is definitely one of those that may improve quality of life, improve survival, and hopefully help to reduce the need for frequent transfusions in these patients. But again, problem is that it's only a bandaid. Just like lenalidomide is a bandaid. It's trying to help them to make better red blood cells. Azacitidine is trying to help to stop some of these blasts from continuously to undergoing ineffective erythropoiesis. The only thing you can really do is get a transplant. Yeah. Problem is that there's 70, 80-year-old individuals probably their fitness level's kind of like lower, it's harder to push something like that in an MDS patient. Sure. But you could possibly? You definitely could. Okay. Yeah. In certain scenarios that's the only potential cure. That's really the only thing that you could truly do is to get rid.'cause the problem is what MDS does is, you take a hematopoietic stem cell mutations occur like the 5q turns into this weird dysplastic cell that then becomes the stem cell. That makes, ineffective red cells, ineffective platelets, ineffective white blood cells. Yeah. Then what it does is it sends signals to kill your normal hematopoietic stem cells, so then if you kill those hematopoietic stem cells, you don't have those to make normal red cells, normal white cells, normal platelets. So that's where we kind of come in and bring in a normal type of hematopoietic stem cell, and hopefully in that goal you'll be able to trigger the production of normal processes. So we've talked about a few drugs so far. We've talked about a stem cell transplant being curative. What about supportive care? What supportive measures would you advise here? Yeah, so I would keep trying to, so obviously I, for this patient, lenalidomide, would be the goal. If he didn't have the 5q deletion and stuff like that, then I'd probably do azacitidine. But the supportive stuff is just really treating the cytopenias. So if they have low platelets. You obviously have to follow the thresholds that we talked about in the blood transfusion lecture. So if it's less than 10,000 and they're asymptomatic, you can do that prophylactically to prevent spontaneous hemorrhage. If it's less than 50 and they are bleeding, then you can give them platelets. If they're getting a neurosurgical procedure and it's less than a hundred thousand, then you can give them platelets. But otherwise, that's really, it's just platelet transfusions, just for particularly based upon that threshold. packed red cell infusions, you could do that depending upon, again, what's the threshold? Are they less than eight and they're symptomatic because they have underlying diseases that reduce oxygen supply? Then you give them  packed red cell Unit for, getting them above eight. Are they asymptomatic? No. True kind of risk factors that make them need higher oxygen delivery. Then you can go less than seven. Are they. Bleeding out hemodynamically unstable, then you just give them what you need to get them right. But that's the big thing for that. The only thing I get concerned about is when a patient's getting frequent transfusions, I worry about hemochromatosis. So sometimes you may have to give like iron chelating agents sometimes to come in there and like deferoxamine is a good one that we may give to help to bind up some of that excess iron so it doesn't deposit into our tissues. Because if that does, it can cause, cardiomyopathies, it can cause pancreatitis, it can cause bronzing of the skin. It can do it into the joints. A lot of different areas could be affected and that can cause a lot of different complications. The iron chelation and making sure to prevent iron overload is really important. 100%. Just kinda like thalassemia sickle cell anemia patients, those are patients who get frequent transfusions, right? And so we always try to be very cautious and watch out for that secondary hemochromatosis or iron overload. And so in those scenarios, we will commonly give iron chelating agents. Makes sense? Yeah. I haven't seen this used. I'm sure it can be, but I, you gotta be careful. Sometimes colony stimulating units or colony stimulating factors can be given to help to boost up your production of white blood cells. But I don't say that it's a common one that's given. But if you do have recurrent infections in your white cell lines really depleted, you could do that to potentially help. But that's where I would say in certain scenarios, colony stimulating factors could be potentially utilized. All right, well, how do we monitor or detect progression? Ooh, that's good. So I think the key thing is that you want to see if your therapy is working. A lot of this anemia is the most common thing. So let's say I have a patient who comes in, they got macrocytic anemia. We go through the whole algorithm. All right, let's check the peripheral blood smear. Okay. No hypersegmented neutrophils. So this is a non-megaloblastic guy. Let's look at that. Peripheral blood smear. Oh, it's got the weird, like Pseudo-Pelger-Huet. Okay, then that's probably MDS. All right, let me check a bone marrow biopsy. Oh, definitely. There's lineage and there's a hypercellular marrow. There's some blast there. Okay, cool. Let's check the cytogenetics. Oh, there's a 5q deletion. All right, let's. Transfuse 'em if they need, oh, they keep needing transfusions. All right let's check the EPO levels less than 500. It is, okay, start them on erythropoietin, oh, they're still needing transfusions. Okay, let's give them lenalidomide from there. Your goal is the hemoglobin ever becoming stable and do they need less frequent transfusions? So that's the key, is just keep monitoring their CBC and making sure that thing is getting better. The other thing is you also wanna keep an eye on their CBC because again, what I told you, the most common reason these patients usually die is because they die from complications of the cytopenias. So you wanna watch and make sure that the platelets aren't dropping too much. You wanna make sure that the white cells aren't dropping too much. So keep a close eye on those. And then the other thing, I again, more likely to die from the complications of the disease before developing AML. But sometimes you may have to do a like recurrent or at least serial bone marrow biopsies if they're getting worse. If their cytopenias are getting worse, you may have to say, did they convert? Is the number of blasts that are in their bone marrow now greater than equal to 20%? If it is, it's AML. So that's something to consider is if they start having worsening cytopenias. And they're getting worse. You may need to ask yourself the question, is this AML?'cause if it's AML, that's a different type of treatment process.'cause then we have to start considering potentially like chemotherapy. But that would be the most important things to really kind of check on in this scenario. So in summation, if you could go through maybe a five step approach in treating MDS, how would you do it? First thing? You get once you get that patient who comes in with either pancytopenia or more often macrocytic anemia, that's non megaloblastic. You gotta confirm it with a bone marrow biopsy. You have to have tissue confirmation. Once you do that, figure out what is your risk. You check that by looking at the cytogenetics 5q deletion or not cytopenias. How bad are they? Blast percentage. That gives you an idea of what you're gonna do for this patient. If they're in that low risk, they have that 5q deletion. That's the patient who's gonna respond to Lenalidomide and just the supportive care that you would provide. Platelet packed red cell infusions, iron chelation. If they're getting a lot of transfusions and maybe colony stimulating factors, they're high risk. They don't have the 5q deletion. They have lots of blast cells, right? They have severe cytopenias. That's as azacitidine. Continue with the supportive care and figure out with your transplant team. Can I get them a bone marrow transplant? Otherwise everything else is just your supportive care measures. Trying to make sure that you're helping them to stay where they need to be with their thresholds. Do they need a packed red cell infusion because of where their hemoglobin and symptoms is? Platelet transfusion because of their symptom and platelet level, and again, making sure that these things are working by trending their CBC. Trending potentially a need for a bone marrow biopsy if they're getting worse and seeing if they've converted to AML.. Those are the big things to consider. Well then finally, Zach, let's talk about outcomes and prognosis. What do you think? Well, again I think this is one of those diseases where sometimes a patient can have MDS and they can be sometimes, pretty much mild, it could, sometimes you could be asymptomatic, and again, the only symptoms that you have may be some symptoms of mild anemia. Sometimes it can range potentially to where it's pancytopenia. Again, I think the biggest takeaway for this is that MDS sometimes can be relatively asymptomatic and mild, and the only present with anemia. Sometimes they can present with severe cytopenias. The worst kind of case scenario is the conversion of this condition into AML. And so I think the prognosis kind of just depends and their outcome kind of depends on where they lie within that risk stratification. Yeah. That's kind of crazy to think about how variable of a disease this is. Exactly. A pretty large spectrum you're working within. Exactly. And that's the biggest thing to consider. And again, I, it kind of goes back that oftentimes. We just do supportive care in what we talked about here, just because it's, again, it's sad to say, but most of the time these patients usually die more from the complications of the disease itself. From the cytopenias. Yeah. Than they do from the conversion to AML. And once you get AML, you're talking about, leukostasis, you're talking about DIC, you're talking about tumor lysis syndrome. You're talking about some severe stuff. So I think in that point it's it just depends upon where they lie in that risk. Gotcha. Well, that really summarizes what we've talked about here on MDS. Do you have anything else you wanna kind of go over? I think just the biggest thing is MDS is one of those insidious ones where you don't always think about, biggest thing to think about as a patient either with two things. One is an isolated macrocytic anemia. Second is pancytopenia. Those are the really important things to be thinking about. You have to get a bone marrow biopsy to con confirm it. Once you see Pseduo-Pelger-Huet, neutrophils on the peripheral blood smear. Definitely think especially for the exam, bone marrow is the way to go. Determine their risk. Where do they fall? How aggressive do we need to be with the treatment? By looking at cytogenetics blast percentage and the degree of their cytopenias. Always remember the exam. 5q deletion, Lenalidomide. Yep. No, 5q deletion. More likely the Azacitidine. All the other stuff is supportive care, and that's really what it comes down to for this patient. Well then that does it for MDS. Yeah, that's another episode done. That was awesome. I think this is a good quick one, and it kind of gives you the idea that. MDS is sometimes it's kind of forgotten and there is very common kind of insidious presentations of it, and we shouldn't miss it just because, someone's a little bit older and it's important to make sure that we identify this and reduce the potential poor outcomes and really help to improve their quality of life and increased survival for these patients. Yeah, especially as you're at this age, there's nothing better than helping improve your quality of life. That's. That's great to hear. Yeah, exactly. But yeah, I think that's the big things. There's a lot of other things that happen with MDS, like there's this World Health Organization like classification system and it gets really detailed. And I didn't wanna discuss it here because I don't know if it bears much weight and squeeze into what we wanna talk about, but I really think this gives what we need to know about MDS for clinicians for now. Hey, it sounds good to me. Thank you. Yeah. Yeah. Thank you guys and I hope that you guys liked this podcast. I hope it made sense. I hope that you guys truly did enjoy it. And again, if you did and you like what we do, support us. If it's on YouTube, hit that like button, subscribe, comment in the comment section. If you're listening to us on any of the other platforms like Apple or Spotify, again, share this to your friends. I think that this can really help out a lot of you guys who are in medicine. Also, if you want more, check out our website. We have a really good website that we offer notes, illustrations, quiz questions, lots of things that I think are really just all inclusive to you guys knowing the topic. So with that further being said, I just wanna say thank you guys. Love you guys, and as always. Until next time.