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Did you know that conditions like myelodysplastic syndrome, myeloproliferative neoplasms and acute myeloid leukemia affect thousands of people each year, often with vague symptoms like fatigue, infections or unexplained bruising?
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These myelodysplastic conditions not only pose diagnostic challenges, but also have significant implications for treatment and prognosis.
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Understanding them is crucial for any clinician aiming to provide timely and effective care.
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G'day and welcome to Aussie Med Ed, the Australian medical education podcast designed with a pragmatic approach to medical conditions by interviewing specialists in the medical field.
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I'm Gavin Nimon, an orthopaedic surgeon based in Adelaide, and I'm broadcasting from Kaurna land.
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I'd like to remind you that this podcast is available on all podcast players and is also available as a video version on YouTube.
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I'd also like to remind you that if you enjoy this podcast, please subscribe or leave a review or give us a thumbs up, as I really appreciate the support and it helps the channel grow.
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I'd like to start the podcast by acknowledging the traditional owners of the land on which this podcast is produced, the Kaurna people, and pay my respects to the elders, both past, present and emerging.
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Today we're visiting an important area of hematology with a very special guest, Dr Joanna Czajwinski.
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She's returning to the podcast.
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Last time, Dr Czerwinski provided us with a comprehensive overview of lymphoid malignancies.
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This time we're shifting our focus to explore the fascinating and complex world of myeloid dysplastic syndromes and malignancies.
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Whether you're just curious about the role of genetic testing or the complexities of managing these conditions or symptoms should prompt a referral to a hematologist.
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This episode promises to be informative and engaging, so grab your coffee, take a seat and let's dive into the world of myeloid malignancies with Joanna Chwinski on AussieMedEd.
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I'd like to remind you that all the information presented today is just one opinion and that there are numerous ways of treating all medical conditions.
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It's just general advice and may vary depending on the region in which you are practicing or being treated.
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The information may not be appropriate for your situation or health condition and you should always seek the advice from your health professional in the area in which you live.
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Also, if you have any concerns about the information raised today, please speak to your GP or seek assistance from the health organizations such as Lifeline in Australia.
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Thanks, Joe.
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Thank you very much for coming back on Aussie Med Edge.
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This time we're going to talk about myeloid conditions.
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I believe there's two sort of different pathways the haematology conditions can undertake.
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We've talked about lymphoid conditions previously which went down the pathways of the cells that form T cells and B cells.
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Now we're going to talk about myeloid conditions, which are the stem cells that produce red cells, platelets, etc.
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Perhaps you can just explain what the myeloid stem cell line is like and how it divides and how it's affected as well.
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Start off and down that pathway, Jo.
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Yeah, of course.
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Thank you for having me again.
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So with the myeloid malignancies it does produce most of the blood components.
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So we originate again from the hematopoietic stem cell and then, as we mentioned in our previous podcast, it divides into either the lymphoid stem cell or the myeloid stem cell, and so it quite easily goes on to the chronic and the acute conditions, like we had previously.
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But in the myeloid stem cell components there are the red cells, the granulocytes, which are things like neutrophils, eosinophils, basophils, and there are the platelets, and so you can quite easily see that any damage to the myeloid stem cell can affect quite a lot of the blood components and is what causes a lot of the cytopenias as well as the cytoses.
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Right, and are there many things that can affect those sort of pathways?
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Is it more just aging and genetic elements, or what are the main factors that affect them?
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So most of the times it's due to older age and genetic damage.
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So most of the conditions are diagnosed above the age of 65.
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But in particularly the younger cohorts under the age of 50, there are additional risk factors that we look out for.
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These can be things like exposure to previous chemotherapy and radiotherapies.
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It can be radiation exposure just in general, and it can also include certain medications that we don't really think about as chemotherapeutics but fall under the class of, like your disease, modifying agents for rheumatoid arthritis and other inflammatory conditions.
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There is also a small group that it can be inherited conditions passed along through generations.
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What's your main ways of classifying these conditions and how do the classifications affect the presentations?
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Perhaps?
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So certainly I start off with acute and chronic, because in the acute category you've got acute myeloid leukemia and acute promyelocytic leukemia.
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Those are your only two acute entities, realistically.
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And then majority of the other myeloid conditions falls under the chronic banner.
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And in the chronic banner you've got the myelodysplastic syndromes and the key word there is dysplasia, meaning that the cells don't look or act normally.
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And then you have the myeloproliferative neoplasms where the key word is the proliferative part, because most of the time the cells are in overdrive and there's far too much production, and these are further subclassified as well.
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So in the myeloproliferative neoplasms you may have heard of polycythemia vera, where you make too many red cells.
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Essential thrombocythemia, where you make too many platelets.
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Chronic myeloid leukemia, where you make too many of the granular sites, particularly the neutrophils and precursors of neutrophils, and myelofibrosis, which is in a way a burnt out version of these myeloproliferative neoplasms, where it initially starts with high numbers of cell counts across the board, but then it burns out and it actually causes cytopenias as the bone marrow scars over.
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And we finally also have an overlap syndrome, where you've got a component that is dysplastic and a component that is proliferative, and this is called myelodysplastic, myeloproliferative overlap syndrome.
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It's a bit of a mouthful.
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One of the problems that we have with the dysplastic syndromes is that you may not have adequate cell counts so they may have cytopenias and with the remaining counts they could be quite dysfunctional.
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So they are at risk of immunodeficiencies, immunocompromised states In the myeloproliferative neoplasms, the polycythemia and essential thrombocythemia conditions where there's too many of the red cells and platelets respectively, you end up having dysfunction from either bleeding or clotting perspective.
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So usually it's not so much that they can't carry oxygen or can't go and make a clot formation, but it's that they try and overwhelm the system a bit too well.
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So is that how most of them will present then with bleeding and bruisings or DVTs and things?
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Most of them do present either through incidental blood tests and you can see an elevated platelet count or an elevated hemoglobin.
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But you can also see them in terms of having VTE events, and some of the VTE events can be in strange locations like splanchnic vein.
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They don't necessarily have to be your traditional DVT or PE.
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We talked about lymphoid malignancies that had some splenic conditions and other lumps and lymph node conditions occurring.
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Do you get any of that occurring in myeloid conditions or is it all purely in the bone marrow?
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So when the bone marrow is dysfunctional and either doesn't have the capacity to make cells anymore or has completely scarred over, a lot of the production is taken over by the spleen.
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So a lot of the particularly in the myeloproliferative conditions, you end up getting extra medullary creation of these cells, and this is predominantly in the spleen.
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So you can certainly get splenomegaly in these cases, and in the vast majority of the myeloproliferative cases it's in myelofibrosis, Because in that condition your bone marrow ends up being like one big scar tissue where there's no capacity for cell generation.
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I understand.
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Also you can sometimes present with shortness of breath.
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Now, is that from PEs or is that from the actual cells developing and occurring in the lungs?
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So it's in three parts, depending on the condition.
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So if they're anemic then the shortness of breath can be attributed to anemia.
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If they have something like a VTE, a PEE event, then they certainly can have shortness of breath from that standpoint.
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But the chronic myeloid leukemias and conditions where the granulocytes can be quite elevated you get this sometimes in the acute myeloid leukemias as well, where the total white cell count is over 100 and what can happen in the lungs is that you have a whole host of neutrophils around the lung tissues and their granular products.
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So things like histamine and other cytokines they can release in the lung area and it can present like an acute pulmonary edema situation.
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Or it could also probably look a little bit like asthma, could it in that scenario?
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Yeah, it can.
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And when we go into acute promyelocytic leukemia, I'll also talk about differentiation syndrome, which can present like an acute pulmonary edema as well.
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I understand also you can get acute pulmonary edema as well.
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I understand also you can get some skin itchiness as well.
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Is that from the same sort of process as you get occurring in the lungs, or is it a different sort of pathway?
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It's a similar pathway.
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It's due to cytokine release and sometimes it can be due to the thickness of the blood as well.
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So you often get, in particular in polycythemia vera, you can get itchiness, you can get a redness discoloration of the face.
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People look often quite flushed and they can get quite sweaty as well.
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Okay, so obviously the name polycythemia vera makes you think of redness.
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Is that not just purely because of the actual cells affected, but it's actually the appearance of the person is it?
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Yes, it is Quite plethoric.
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So the vast majority of cases.
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You see, though I think I said previously when we're talking about lymphoid malignancies.
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They were incidental on blood tests.
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Is that still?
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the same case with myeloid conditions as well.
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So in the myelodysplastic syndromes most of these occur above the age of 65, 70, and it's usually on routine blood tests that are done for other reasons and you might only get hints of this condition developing like they may have an anemia of 120 for a male, which is still anemic but is very mild, and the only real symptom that they may have is fatigue and in some ways it can be hard to say you know a 75-year-old that is otherwise fit that this condition is causing a lot of their fatigue.
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In the myeloproliferative neoplasms there's some of my patients where it's identified because they are again fatigued for different reasons or they have developed a VTE event.
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But we do see some of them come in with hemoglobins of 170, 180, and you can't determine whether that figure on its own is the polycythemia vera that comes from the bone marrow or whether it's secondary to diuretics, dehydration, chronic airways diseases, sleep apnea.
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Okay, Of the particular different classifications.
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Obviously you talked about acute versus the chronic episodes.
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How does the acute presentation vary to a chronic presentation?
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The way that it presents is often florid in emergency department and it usually only has a prodromal illness of maybe one to two months at most.
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So one of my cases that I'd had had been having back-to-back viral infections or sinus infections for a period of seven weeks before he presented to his GP and at that point he had a white cell count of over 100.
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So he was called in from SA Pathology.
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He was called in to present to emergency department and get quickly worked up and he ended up having an acute myeloid leukemia and the clue was that he was getting recurrent infections and not getting over them.
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Right and a chronic one is more just, purely a slow, insidious sort of presentation which is picked up more on blood tests.
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Yeah, so most often it's anemia that's been there for say 12, 18 months for the myelodysplastic ones or the myelofibrosis cases and conversely, on the other, myeloproliferative neoplasms like the polycythemia vera and essential thrombocythemia.
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Again it will be mildly above the mark but chronic, and the GP has done a few different tests and can still not figure out why this is.
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Platelets of 500 to 600, hemoglobin of 170 to 180.
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In those sort of mild categories where you could attribute it to they were a bit dehydrated or they've recently had an infection you could attribute it to they were a bit dehydrated or they've recently had an infection.
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So we've got these patients presenting with some vague symptoms and they're picked up on an abnormal blood test.
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Once the abnormal blood test is standard, I presume complete blood examination is performed.
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What other investigations are required?
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Are they the same as lymphoid type conditions or are there anything specific you'd do?
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Let's just go through them all again, just to remind me as well.
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Yeah, absolutely so.
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A complete blood examination with a blood film is a key, particularly for the myelodysplastic syndromes and the acute leukemias, because that's going to be pretty diagnostic quite early on if they have these conditions, and particularly the acute myeloid leukemia.
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If you have a blood test at nine in the morning, it gets sent through to SA Pathology.
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You've got someone looking at it a few hours later and bringing a patient into hospital later that afternoon.
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So it's quite a rapid turnaround for the acute leukemia.
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For the myelodysplastic syndrome, there might be the appearance of dysplastic neutrophils, for instance, and that will be the first clue to the diagnosis.
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So blood film is definitely essential For both the myelodysplastic syndromes and the acute leukemias.
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I do flow cytometry because that helps to determine what the blasts are.
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Are they myeloid origin or are they lymphoid origin?
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Now, if we're going down the acute leukemia pathway, that is usually managed in hospital and investigated in hospital.
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But the things that we want to know is what is their kidneys doing, what is their liver doing and what is their cardiac health like?
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Because those three things determine their ability to tolerate intensive chemotherapy.
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For the myelodysplastic syndromes it is helpful to have creatinine and is helpful to have liver function tests predominantly because the main treatments involve the kidney in the filtration system.
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So we need to have adequate renal function to be able to deliver treatments.
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For the myeloproliferative neoplasms, the renal function and the liver function are less required in terms of being able to deliver treatments, but it is still a good thing to help with your differentials as to what may be causing, for instance, your polycythemia vera.
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If you've got an appearance of dehydrated kidneys, then it might be due to diuretic effect, as an example.
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So the other tests that have become more recently available that a hematologist could order includes the karyotyping or the cytogenetics, and that's usually done on a bone marrow biopsy specimen.
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And they may also do a genetic panel looking at molecular mutations and again, that's predominantly done on the bone marrow.
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Having said that, in some of my older frail patients where I don't think I'll be able to adequately give them treatment, I can do the same genetic panel from their peripheral blood as a bit of a prognostic indicator as to how long I've got with the patient and what else I can do to improve their quality of life.
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So certainly, the acute leukemics, we all do bone marrows.
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On the myelodysplastic syndrome you need to have a bone marrow to access treatment.
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If you're going down a treatment pathway and for most of the myeloproliferative neoplasms it's good to have bone marrow, but not essential.
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The only essential ones that you need is myelofibrosis, because, again, treatment is reliant on that diagnosis being confirmed, and the chronic myeloid leukemia because it is a way that you can monitor effectiveness of treatment over time.
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But the majority, like the polycythemia vera and the essential thrombocythemia, it's good to have at diagnosis but not essential to begin treatment.
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Excellent.
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Are there other tests you might do as well, like apart from the bone marrow or the blood picture?
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Are there things like CTs or ultrasounds that are also required?
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So a good clinical examination for splenomegaly is important for the myeloproliferative neoplasms and in clinical trials they will always use splenic size to determine how people are responding, particularly for myelofibrosis.
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So a lot of people have a CT scan or an ultrasound at baseline and then serially performed to track response.
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But if you can feel the spleen at the beginning and you can measure, you know, for my fingers something starts out as four finger breaths and goes down to two finger breaths.
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I know that they're responding to treatment and I don't need radiology to tell me that.
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So it's not required to have a CT scan.
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If they're going to have intensive induction chemotherapy for the acute leukemia we often get a CT sinuses because they're at a lot of risk of sinus infection and particularly invasive fungal.
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So we may sometimes in hospital also do a chest CT as part of that.
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Right.
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So that's really the full workup.
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Then you can actually do fairly straightforward investigations.
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Then with the bone marrow biopsy and a few other investigations you can get the baseline of what you really need.
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Absolutely.
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How do you progress from there then?
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What's the next step, Once you've got your biopsies and you've got your blood picture?
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you've done your examination, what's the next step?
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So I guess if we're looking down the pathway of treatment, I need to get the infectious serologies ticked off, like your hepatitis B, c and HIV, and for the acute leukemias it's helpful to have a uric acid for tumericis response, particularly because the myeloid cells are generally bigger than lymphoid and when these guys break apart and burst they do release toxic products similar to the lymphoid cells.
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So we still need to think about tumor lysis syndrome in the acute leukemia status.
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With the chronic conditions, again, if I'm embarking on treatment I want to know their infectious serology.
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And then it's determining their age and fitness and putting in the different characteristics into like a prognostic scoring system to determine what treatment is best.
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And this can be different for whether they're young or old, whether they have transfusion dependency or not and whether they've had a VTE event or not when we're talking about the chronic one.
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I might just stop you there for two seconds and just ask you, because you've just raised some great thoughts that I didn't know about.
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So tumor lysis syndrome is that?
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I presume that you can get gout from that because of the release of uric acid.
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What else does it involve?
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So tumor lysis syndrome.
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I like to think of the acronym of CUP C-U-P-P, where your calcium goes down by 25% from baseline, your uric acid goes up by 25%, your potassium goes up by 25% and your phosphate goes up by 25%.
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So these are the early markers of tumericis and it's what we generally monitor twice to three times a day in an inpatient setting.
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When it's quite deteriorated it will involve the kidneys and you will see renal failure and you will also see complications such as acute pulmonary edema when the tumor lysis syndrome further progresses.
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So having those blood tests twice to three times a day during the early inpatient stay during their initial course of treatment, that's where you're going to be able to pick it up early and give them treatments to reduce their uric acid and reduce those toxins.
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So most patients get commenced on allopurinol and it's 300 milligrams a day and they continue it for the first seven days of intensive induction treatment.
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Why is it important to know about the infection status, the hep B, C and HIV.
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Why is that important?
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Because they become so heavily immunocompromised with their treatments.
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You want to detect whether they've got a chronic hepatitis that you can treat simultaneously or just prior to initiating your induction treatment, and the prophylaxis may also change.
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So, for instance, if you have a HIV patient, you want to be putting them on antiretrovirals and you want to make sure that they don't interact with your treatment plans.
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So, jo, moving back on to talking about the treatment plan, once you've done your standard workup looking for infections and also checking for tuberculosis syndrome and being prepared for it, what's the next steps?
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How do you progress with treatment following that?
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If we focus initially on the acute leukemias, if they have a stock standard acute myeloid leukemia the first things that we want to do is bring down their white cell count.
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If it's elevated down to less than 25 so that we can start induction chemotherapy, and this is to try and reduce that risk of tumerosis as well as to try and reduce the risk of any acute pulmonary edema or any other complications from things like differentiation syndrome or, again, the tumerosis effect.
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So what treatment is determined is based on patient age and fitness.
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So if they're an under 70 year old, we're usually offering intensive induction therapy, which is what we colloquially call 7 plus 3, which involves seven days of citarabine and three days of dawnerubicin or other anthracycline chemotherapy.
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So the way that this is delivered is simultaneous seven and three, so it's a total of seven days duration of chemotherapy.
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But because this is such an intensive chemotherapy and aims to clear out everything from the bone marrow and start from scratch, it does take about two to three weeks for recovery from this kind of intensity of chemo, and so most patients will be admitted for the entire month during their induction therapy and they will have to work through any complications, most commonly infections, after the seventh to tenth day and upon recovery of their blood counts at day 25 plus, they're usually scheduled for another bone marrow to see how well that job was done in clearing out their leukemia.
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And if they have achieved a remission so less than 5% blasts in their bone marrow then they go on to consolidation therapy and then the following steps after that is dependent on what risk category of leukemia they have.
00:23:30.160 --> 00:23:42.579
So if they have a high risk leukemia where they've got multiple mutations or very bad mutations, these patients will generally try and get onto the allogeneic stem cell transplant pathway.
00:23:42.579 --> 00:23:47.446
And most of the time we don't cap it by age.
00:23:47.446 --> 00:23:54.243
But generally speaking there are not many 75-year-olds that would be able to tolerate that kind of treatment.
00:23:54.243 --> 00:24:01.807
Broadly speaking, somewhere between 70 and 75, with their fitness level and their comorbidity index.
00:24:01.807 --> 00:24:06.423
That will determine who gets allowed to go to an allogeneic transplant.
00:24:06.423 --> 00:24:13.184
And that process involves usually high doses of chemotherapy to completely wipe out the bone marrow.
00:24:13.184 --> 00:24:25.983
And then you have a replacement bone marrow stem cell environment from another donor, usually a sibling, sometimes it's an unrelated donor, sometimes it can be a parent or a child.
00:24:27.046 --> 00:24:35.250
With transplants in the myeloid conditions, do you have to go on long-term immunosuppression for the use of them, like you do with kidney transplants?
00:24:35.519 --> 00:24:42.923
So I like to think of allogeneic transplants as the only circumstance where you are usually not on long-term immunosuppression.
00:24:42.923 --> 00:24:59.625
You are certainly on immunosuppression for the first 100 days, and it's usually things like cyclosporine, tacrolimus, the usual anti-rejection medications, and then after day 100, when that risk of acute graft versus host disease has subsided.
00:24:59.625 --> 00:25:07.868
That's when, if things are going well, they generally start to taper it down over the subsequent three months, so usually by six months.
00:25:07.868 --> 00:25:19.909
If it's gone all well, patients are usually able to come off of their anti-rejection meds and their new bone marrow and their new blood type is completely ingrained into their own bone marrow space.
00:25:20.549 --> 00:25:22.442
Does that mean that's really interesting?
00:25:22.442 --> 00:25:26.441
Does that mean like you might start off as an A negative and become back as a B positive?
00:25:26.820 --> 00:25:27.301
Absolutely.
00:25:27.301 --> 00:25:28.903
That's what exactly that means.
00:25:28.903 --> 00:25:30.968
That's crazy.
00:25:30.968 --> 00:25:45.619
There's obviously a lot of high-tech involvement with regards to that because, if you can imagine, we talk about transfusion reactions being incompatible blood and we're talking about incompatible bone marrow sources of blood.
00:25:46.220 --> 00:25:47.503
Wow, that's amazing.
00:25:47.503 --> 00:25:50.313
Okay, all right.
00:25:50.313 --> 00:25:54.205
Well, it's one of the most interesting facts I think I've learned in the whole four years.
00:25:54.205 --> 00:25:56.713
Truly All right.
00:25:56.713 --> 00:25:59.923
So that's for the acute stage, the acute conditions.
00:25:59.923 --> 00:26:03.430
What happens in those patients over 70 or 75?
00:26:03.430 --> 00:26:08.104
In the acute stage, they're unfortunately not going to tolerate the treatment very well.
00:26:08.924 --> 00:26:15.694
So a few years ago there became available this protocol called azacitidine and venetoclax.
00:26:15.694 --> 00:26:43.152
Now azacitidine I'll speak about again later because it's involved in myelodysplastic syndromes, but it's a hypermethylating chemotherapy agent that is given as a subcutaneous injection for seven days every cycle, and each cycle is usually 28 days, and this is paired with a BCL-2 inhibitor, so an anti-apoptotic marker, and that is a tablet therapy that is taken continuously.
00:26:43.152 --> 00:26:49.692
And even I think my oldest patient is in their mid-80s and is tolerating that treatment protocol.
00:26:49.692 --> 00:27:05.671
So again you would go through this induction treatment where you're very quickly ramping up to the maximum dose of venetoclax and you're also simultaneously giving the azacitidine and it's a standard treatment course for everyone for cycle one.
00:27:05.900 --> 00:27:08.434
At the end of cycle one you do a repeat bone marrow and again you're seeing how much of cycle one.
00:27:08.434 --> 00:27:12.289
You do a repeat bone marrow and again you're seeing how much of the leukemia you've cleared out.
00:27:12.289 --> 00:27:16.948
Now in most cases the leukemia has been cleared in that first cycle.
00:27:16.948 --> 00:27:36.316
Some additional people need a second cycle of similar intensity and then, once you have cleared out the leukemia, then you can adjust the doses for better tolerability, because most of the time it is an outpatient protocol, it is not needing to remain in because it is that gentler level.
00:27:36.316 --> 00:27:57.548
I've used this protocol also for people that are Jehovah's Witnesses and are not accepting of blood transfusions, because the former the 7 plus 3, renders everyone in need of transfusion, whereas this provides an option for if transfusions are not in that person's religion and also is much more tolerable for the older or frailer person.
00:27:58.510 --> 00:28:04.364
So this is more like a long-term suppressive type of treatment as opposed to a trying or a curative type treatment.
00:28:04.710 --> 00:28:11.203
Absolutely the longest person that I think has been on that combination has been more than 15, 18 months.
00:28:11.203 --> 00:28:33.226
So it is something that treatment protocol for 12 months and they've cleared the bone marrow of the leukemia and they're in a complete molecular remission where you can't detect their genetics from their presentation.
00:28:33.226 --> 00:28:37.557
Whether those patients can actually safely come off of treatment and have a drug holiday.
00:28:38.299 --> 00:28:41.516
We've got obviously using suppressive agents or chemotherapy agents.
00:28:41.516 --> 00:28:43.422
Are there any other types of agents you might use?
00:28:44.211 --> 00:28:48.630
Something that we'll again be talking about, mostly with the myeloproliferative neoplasms.
00:28:48.630 --> 00:28:59.138
But we do use hydroxyurea or hydroxycarbamide as a tablet treatment to cytoreduce or to bring down all of their cell counts.
00:28:59.138 --> 00:29:14.321
So it is a very old-fashioned, very indiscriminatory chemotherapy agent and it's tablets, and it will bring down not only the white cells that you're trying to bring down, but it will also render them anemic and thrombocytopenic.
00:29:14.321 --> 00:29:25.021
So you can only realistically do that for a few days, but that's all you're trying to achieve is a much more tolerated white cell count, so that then you can initiate the effective treatment.
00:29:25.851 --> 00:29:29.916
And this is purely for the acute myeloid leukemia, like promyelocytic leukemias.
00:29:29.916 --> 00:29:35.773
So that's purely the white cell type leukemias Do you get.
00:29:35.773 --> 00:29:36.998
I'm a little bit confused here.
00:29:36.998 --> 00:29:43.636
For a second, can you get acute leukemias involving red cells or platelets as well, or is it purely white cells?
00:29:43.636 --> 00:29:46.058
I'm not making it too hard for myself here.
00:29:46.590 --> 00:29:53.862
It is only with the granular sites, so it is predominantly the neutrophils gone bad essentially.
00:29:53.862 --> 00:29:59.809
So we are dealing with the myeloid precursors, but the white cell versions there.
00:29:59.809 --> 00:30:05.288
Technically is an acute proerythroid leukemia very rare.
00:30:05.288 --> 00:30:07.894
You only hear case studies about it.
00:30:07.894 --> 00:30:24.342
But they are nucleolated red cells that you see in the bone marrow and it has undergone multiple reclassifications so it's now more thought about as an acute myeloid leukemia with a predominance of those red cell precursors.
00:30:24.342 --> 00:30:29.799
And there is an acute megakaryoblastic leukemia and again it's very rare.
00:30:29.799 --> 00:30:44.592
It's very bad news if it occurs in an adult and the prognosis is better if it's in a child with Down syndrome, where there's an increased number of cases in that particular cohort of children with Down syndrome.
00:30:45.134 --> 00:30:51.900
Okay, so the red cell condition, the platelet conditions, are really more on the myelodysplastic or the chronic conditions that we're talking about then.
