Acute Myelogenous Leukemia (AML)

foreign what's up Ninja nerds in this video today we're going to be talking about acute myelogenous leukemia before we get started if you guys actually like this video it makes sense it helps you please support us how can you do that hit that like button comment down the comment section and please subscribe also you guys want some awesome notes illustrations follow along with me during this lecture please go down in the description box below we have a link to our website check all that stuff out all right let's talk about acute myelogenous leukemia I commonly

say AML a lot it's a lot easier to say but email really this disease is a problem with the amount of police's pathway so hematopoiesis the production of all blood cells really that's what it is and it all starts with this beautiful cell right here so this takes place in what it's called the red bone marrow right so in this it starts with this big head honcho called the Hemo the hemocytoplast so the hemocytoplast is like the stem cell for all blood cells and what happens is it differentiates and when it differentiates the differentiates into

two cell lines one is called the lymphoid stem cell and the other one is called the myeloid stem cell the myeloid stem cell then actually differentiates into a couple different cell lines one is it becomes a red blood cell because it actually becomes what's called erythroblast which become a erythrocyte it also will become a platelet and platelets actually what happens is the myeloid stem cell becomes a megakaryoblast and becomes a platelet and the last thing is this can become something called a myeloblast so this is called a Milo blast and what happens is myoblast can

then actually become something called a pro Milo site and then it can differentiate into completely fully functional granulocytes and there's three different types here one two three this is called a neutrophil all right very very powerful cell this one is called a eosinophil and this last one here is called a basophil and these three collectively excuse me is called a specific group called granulocytes okay so these three here are called granulo granulocytes now just to quickly go over the rest of the amount of police pathway lymphoid stem cells actually do become something specific called a

lympho blast this is not important to this lecture when we start talking about something called all and CLL it will become important but these lymphoblasts actually do further differentiate and they become something called B lymphocytes and the other one is called t lymphocytes but here's really what's interesting and a patient who has what's called a AML or acute myelogenous leukemia the problem is right here going from the myoblast to the pro myelocyte and then into these actual functional white blood cells so you can't actually progress forward so the myoblast continues to keep dividing and dividing

and dividing without differentiating and you get tons of these little suckers and these things crowd out the bone marrow get into the bloodstream go all over to different tissues and cause tons and tons of problems now the question comes what is the reason why the myeloblasts can't actually differentiate into Pro myocytes and then become functional white blood cells let's talk about that reason so there's a couple different causes and out of these there's three particular ones that I want you to remember one could be because again to recap here is our hemocytoplast so this is

called our hemo cyto blast it'll become a lymphoid stem cell don't worry about this process now we want to know that this becomes a myeloid stem cell then this becomes red blood cells platelets or a Milo Milo blast and this is supposed to become Pro myelocytes and then the granulocytes now the problem here is we want to know what is the reason why there's so many of these myel blasts because it's stuck in this state of constant Division and can't differentiate into becoming these particular cell lines three particular reasons one is Maybe there was some

type of DNA mutation and if there was a DNA mutation maybe it caused the cell to mutate in a particular way where it allowed the cell to continue to keep replicating without dying oh how would I do that one way that we could do this is called chemo radiation so if someone has a history of chemoreadiation therapy in their past think about this and the reason why is Imagine here from the chemo radiation here's some DNA I hit that DNA with the chemo radiation and I cause a mutation that mutation then causes this particular Gene

here maybe this Gene allows for the cell to continue to keep replicating and dividing so now there's a mutation there's a mutation from this chemo radiation and this mutation now allows for the cell to continue to keep replicating so it allows for excessive DNA replication and cell division without the cell actually dying it's able to evade apoptosis that's one particular reason the second one is it's usually some type of genetic abnormality and there's two particular ones I want you to remember so genetic abnormalities so genetic disease if you will two that I want you to

remember that of a high Association particularly with AML one is called Down syndrome and so down syndrome what are the particular genes or apologize the chromosomes that are really affected here in Down syndrome it's usually trisomy 21 so there's three particular chromosomes of 21 the 21 chromosome there's three copies of it so they call this Trisomy 21 and these have a high risk of potentially causing AML but here's the really really important one I want you to remember there's a subtype so AML has a subtype and this is really really important it's called a PL

acute Pro myelocytic leukemia acute Pro myocytic leukemia and this one is due to what's called a 15 17 translocation and this is important I can't stress this enough I actually want to highlight out this one so this one is probably one of the more important causes to remember now what happens here is let's say here you have chromosome 15. here you have chromosome 17 and they start swapping some of this actual their genes when they do this they form like a fusion Gene so I say here's a fusion Gene as a result of them kind

of swapping the chromosomes and this Fusion Gene acts like this mutated Gene up here and this mutated Gene allows for them to continue to keep replicating and replicating and replicating and replicating without the ability of dying and this allows for the cell to continue to keep replicating without actually truly differentiating this is a problem because this specific Gene here is called the PML Rara Gene so the PML retinoic acid receptor Alpha Gene so these are really really important things to remember specifically 1517 translocation and PML Rara genes there's one last clause and this last one

is usually due to some type of bone marrow disorder and so there's a very specific type of bone marrow disorder okay so if someone has a underlying bone marrow disorder this has the potential to progress to AML and there's two particular types one is called myelodysplastic syndrome so myelid is plastic syndrome is a type of syndrome which they don't have a lot of blast cells in comparison to acute myocytic leukemia and what happens is over time this disease progresses progresses and progresses to where it can become AML there's one other disease we talked to we'll

talk about this one in that video but CML CML over time can actually convert into AML and so these are two big things that I want you guys to remember here okay so the reason why you can have tons and tons of mild Blaster because you cause some type of mutation or Fusion Gene that could be due to chemo radiation it could be due to Down syndrome big type of chromosomal translocation is 1517 with the PML Rara gene or it could be an underlying bone marrow disorder that is progressed to AML now let's talk about

what are the consequences of having tons of these mild blasts in the bone marrow and in the blood and in the tissues all right so now we're going to move into the next part which is again why are there so many of these mild blasts within the actual bone marrow what was the reason why again it could be due to some type of underlying chemo radiation causing mutations or a genetic abnormality that could lead to a kind of a fusion Gene with a specific one that was the PML Rara Gene which is due to the

1517 translocation CNN APL or there's some type of underlying bone marrow disease that's already present and it just progresses to email MDS or CML now in this situation you got all these mild blasts just like replicating like bunnies in the bone marrow they're taking up so much space in the bone marrow that it starts hogging nutrients for other kind of cell lines and starts occupying all that so much space that you aren't able to allow for replication of other cell lines to occur so now red blood cells start decreasing the number platelets start decreasing a

number and you just got you know these tons and tons of myeloblasts so now the question then becomes okay what's the downstream effects all right so you have tons of myeloblasts the problem about having all these myeloblasts is that they are not functional they are decreased they are not functional white blood cells so you aren't allowing for these to actually become neutrophils eosinophils basophils so they are not functional white blood cells they don't have the ability to undergo phagocytosis or kill parasitic worms or trigger inflammatory reactions and so because of that you have a high

risk of infections so now the downstream consequences of this is that there's now a high risk of infections and this is usually one of the ways that people die from this disease this is a very high mortality effect and what are some of the ways that they can actually end up having these infections one is it can cause infection of the lungs pneumonia tends to be one of the most common ones it can cause infection of the particularly the bladder or the kidneys and this can cause UTIs or it may affect the skin and cause

cellulitis so it may cause things like cellulitis or abscesses things to that effect and it cause more infections but that's one Downstream negative consequences of this actual acute myelob sorry myelogenous leukemia's high risk of infections now the other thing is that you're actually dropping down the number of red blood cells so we call this anemia now anemia whenever you have less red blood cells you don't deliver oxygen to the tissues and so because you don't deliver oxygen to the tissues you need oxygen to be able to produce ATP and so the energy Productions actually start

decreasing so you become super fatigued so that's one potential feature is fatigue the other one is that blood right if it's oxygenated should have a good power to the it should actually give a good cue to the skin a good reddish pinkish shoe to the skin but if you have less of that hemoglobin less oxygenated hemoglobin it doesn't give that nice kind of like reddish pinkish shoe to the skin and so that you actually start looking like you're pale that's unfortunate so pallor and then also dyspnea so dyspnea can be a feature with severe anemia

though okay so these are potential features that may be suggestive of anemia but you need to get a CBC to really confirm that now the other thing is when you have low plates what is this called thrombocytopenia and again the question then becomes why is there low levels of these lines it's because again there's so many myeloblasts that are crowding out the bone marrow that there's not enough nutrients for the red blood cells not enough nutrients for the play there's not enough space for them as well when there's low levels of platelets now you have

risk of bruising and bleeding because these are supposed to like stop you you're supposed to help to initiate clotting mechanisms but if you don't have these you can initiate clotting mechanisms and now you end up with bruising so like little like blood leaking out of the capillaries into your skin you have a lot of bruising petiki eye peppera ecchymosis or you're in a bleeding epistaxis gingival Bleeding full on GI bleed that's a terrible situation so watch out for any evidence of bruising and bleeding and again the terms that they may throw on the actual exam

is things like petechiai perpera ecchymosis or full-on bleeding epistaxis gingival bleeding or GI bleeding so watch out for these as potential features secondary two thrombocytopenia but you need a CBC to confirm that okay the next thing this is actually interesting so because the mild blasts are actually crowding out so much space so again the reason why this is less space is what I want you to think about less space is the reason why there's less platelets but here's the other problem you have so many of these mild blasts replicating like bunnies what it does is

when you have tons of myoblasts it actually starts to cause expansion of the bone marrow so it expands the bone marrow because you have to make space and when you expand the bone marrow it actually activates a lot of like nerves that are actually present and kind of innervating the bone marrow and because of that this can actually precipitate a bone pain and this came to look at a lot of different ways this may present like back pain this may present like actual like chest pain kind of like a sternal pain or it may actually

present with them like limping right so that's another potential way to think about that so watch out for this is another potential feature these are the big things that I really want you to think about due to the high amounts of myoblasts that are actually present within the bone marrow now let's say that the mild blast to say okay I've had my time in the actual bone marrow time for me to go out and start you know jacking things up in the bloodstream so it starts leaking out of the bone marrow and into the bloodstream

and look you got these mild blasters flooding through your bloodstream they go out there and start kind of just causing tons and tons of problems what kind of problems here's one and this is usually oncological emergency usually this is actually seen whenever the white Bloods are the myeloblast amount is so high that it can actually literally clot off blood vessels that's scary so imagine there's a blood vessel Supply in the brain a blood vessel Supply in the lungs blood vessels applying the retina and even technically the veins that actually drain the penis these can be

problematic areas so whenever the actual mild blast number is greater than or equal to at least one hundred thousand they've become so much that they actually start clogging up the actual blood vessels to particular areas of the body and because that you start seeing Downstream occlusive effects of hypoxemia so if I'm not able to give if I'm blocking off blood flow which is supposed to be going here and giving nutrients and giving things like oxygen but I'm blocking that off so I'm not giving these type of oxygen nutrients to the tissue they can experience hypoxemia

this can look like a headache at first but then it can progress to a TIA or I can present towards a full on ischemic stroke that's terrifying the other thing is you could block off blood flow to the lungs and potentially alter the gas exchange process and this can present as first maybe just as distinia maybe a little bit short of breath and then it can present as full on hypoxemia to the point where it can actually cause acute respiratory failure okay and this could also block off the actual blood flow going to the retina

which may present as maybe vision changes but that can fully go on to complete vision loss so this is terrifying types of things that you want to be able to pick up this is usually a result of leukostasis way more common so you can see this in AML and you can see this in all but it is way more common in AML now the next one this is also a really bad one this is called tumor lysis syndrome now we'll talk about a little bit more in the treatment section but tumor lysis syndrome can occur

under two particular circumstances so tumor lysis syndrome one reason is a patient has a crazy high tumor burden and it can happen spontaneously it's just not as common so we'll put here the two particular situations one is the most common reason and the second one is the last common reason the most common reason is a secondary to chemotherapy so someone receive chemotherapy and just ruptured open a ton of these actual tumor cells the leukemic cells the other one which is less common is actually spontaneous due to high tumor burdens and it's usually secondary to high

tumor burdens it's just not as common and so what I really want you to associate tumor license syndrome with is it's usually a result of treatment of the leukemia okay so that's why we'll get into a little bit more in treatment but what happens is if it were to happen spontaneously and the reason why is you'd have to have like a very very very high number of these myeloblasts they would have to be very very high to the point where they're getting stuck in blood vessels like in leboostasis to actually pop open if this happens

what they do is they start spilling out tons of intracellular contents such as what such as potassium such as phosphates such as uric acid and what is the problem with this the problem is that these can really cause harm to the kidneys these can really do a lot of damage to your poor old kidneys and what happens is is the uric acid is actually nephrotoxic what can do is you can actually form these things called like urate crystals so it can actually form something called crystals they're actually called crystallica crystal-induced nephropathy so it can cause

things like these little crystals to form and these can get deposited into the actual nephron and cause damage to the actual kidney tubules and affect the ability to reabsorb and secrete substances the other thing is that phosphates can combine with calcium and when calcium combines with the phosphates these also form like calcium phosphate crystals like kidney stones and again they deposit and cause a lot of damage to the kidney tubules and eventually this will precipitate acute kidney injury which can look like a patient has low urine output or they may present with a high creatinine

or a high bun and see these are things to think about okay and again problem is usually due to this one is the I'd say the worst case scenario the uric acid but it can also be due to the phosphates and then having tons and tons of potassium in the bloodstream is not a very good thing as well because this can cause cardiac arrhythmias okay so we got leukostasis tumor lysos syndrome what else these can cause a lot of cutaneous manifestation so cutaneous and like mucosal manifestations so cutaneous and mucosal effects and so imagine they

deposit into the skin like into your actual like skin hair tissue what that can do is that can cause something called leukemia acutis so one thing you can do isn't cause leukemia cutis and you know what that looks like take a look at this it actually is pretty cool to see that's actually a terrible situation but leukemia cutus it's a very interesting picture so take a look at that now we see leukemia cutis is one another one is to get actually deposit into the mucosa of the gingiva and this can cause something called gingival hyperplasia

gingival hyperplasia so that's another potential thing to look out for so these are big ones leukemia cutus there's one cute DNA's manifestation and the other one is gingival hyperplasia let's actually take a look at what this looks like the last effect and probably the most fearful and downstream negative consequences of acute myeloid myelogenous leukemia is something called DIC DIC is terrifying and especially in this particular disease so imagine here I have a myeloblast here's my myeloplast and this is usually only seen in a very specific type so I actually have to highlight this this is

DIC only seen in APL go back remind yourself what was APL particularly 1517 translocation with the PML Rara Gene if that happens this is the only particular type of AML subtype that you can see DIC in now what happens is these myoblasts release two particular types of problems one is they can release something called tissue Factor and you guys know tissue factor from the clotting pathway this is actually factor three so it activates the extrinsic pathway and leads to increased clotting and then when you have increased clotting you actually decrease your clotting factors because you

cause so much clotting to occur that you consume so many of your clotting factors so it increases the clotting pathway but then over time decreases the amount of clotting factors that you have present so if you have decreased number of clotting factors now you can't actually clot when you need to clot that's terrifying situation the other problem here is it releases something called TPA so it has a particular enzyme on its actual surface called TPA and what happens is TPA can actually cause lots of fibrinolysis it can break down fibrinogen and fibrin strands and so

now you actually don't have the ability to keep a clot stable and you actually can't form a clot as well that's terrifying as well so now there's tons of fibrino lysis and so that also has decreased ability to clot and so because of that you have a very very high bleeding risk because you're causing tons of fibrinolysis via this particular molecule and you're causing lots of clotting factors to be consumed so this decreased quality factor is secondary to consumption that's important to remember secondary to consumption because you're just going and chewing through them now you

have an increased bleeding risk so the problem is in this disease is they make too much of this too much of this and they have a high bleeding risk and where do they bleed they bleed into the brain this is probably the highest mortality effect or into the lungs and they can also bleed into the cutaneous tissues as well so I see the worrisome finding would be an interest cerebral hemorrhage second one would be a pulmonary hemorrhage and then you know the one that you'd be thankful to actually have even though it's terrible would be

like any kind of bruising or bleeding potentially maybe they had like an IV in and they're bleeding from their IV sites or they're oozing from a lot of different areas that's a big big thing to watch out for so these are the complications and things that you have to watch out for my friends and patients who have AML now we have to do is go talk about how do we diagnose it I'm a friend so now we have a very strong suspicion that a patient may have acute myelogenous leukemia we started off by saying um

it had some history chemo radiation oh they have history of MDS or CML oh okay maybe they have like an unfortunate Down syndrome right that could be potential possibility but that's potentially the cause of it then they end up with features of high myeloblast within the bone marrow maybe they end up with a kind of like fatigue Disney appalar maybe they end up with bone pain maybe they end up with a lot of bruising and bleeding high risk of infections they have a lot of infections that are unfortunate for them and aren't easily explained they

also have a lot of other features such as leukemia cutis or gingival hyperplasia they have other things like leukostasis and DIC and tumor lysis syndrome features if those are possible you should start working them up for AML so first thing is a CBC with peripheral blood smear that's a good kind of screening test and the reason why is it kind of confirms or supports the things that we actually talked about in the path of is so for example because these myoblasts are crowding at the bone marrow what would happen to the red blood cell line

it would drop right so we would see features of low red blood cells that's one feature we would see low levels of platelets and we would see potentially see what for the white blood cells these can be variable believe it or not so that's the weird thing for the white blood cells for the actual true neutrophils eosinophils basophils all those particular cells the the variable variability of the white blood cells is what's very very interesting in this disease so it literally could be high and they could have leukocytosis or it could be low and they

could have leukopenia so it's not a a true reliable diagnostic marker but the low red blood cells and low platelets secondary too decrease space because of all those myeloblasts crowding at the bone marrow does support the actual features that we talked about then we need to see lots of Mile less so having infections yes you could prove pneumonia but there's a lot of the reasons people can have pneumonia we actually want to see the actual myoblast and so what we actually want to do is is we actually want to take okay lots of these mild

blasts we know that they can cause potential infections because they're not functional but what if I see them on a smear a peripheral blood smear they won't look like normal neutrophils eosinophils and basophils all those so they'll look weird they'll look not differentiated and so that would be a potential sign so what I do is I do a peripheral blood smear and on that you'll see tons of these myeloblasts there'll be just a plethora of these puppies and that would be enough to support high myeloblasts low platelets low red blood cells boom that's that's right

there that's our first step if we have these present right so if I see low red blood cells supporting anemia low platelets supporting thrombocytopenia and I see lots of myoblasts on my peripheral blood smear already I have a very strong differential a very strong suggestion of AML then what I can do is I can actually confirm it so once I've done this test I'm going to do a confirmation or definitive so this will be our definitive diagnosis this would definitely tell us if a patient has AML so what I'll do is I'll do a bone

marrow biopsy I'll take a piece of the actual bone marrow and what I should see is I should see a ton of these myoblasts within the bone marrow so much of them less red blood cells less platelets variable numbers of white blood cells differentiated white blood cells but I'm going to see tons of these these myoblasts we say that if there's actually at least greater than 20 of these myeloblasts within the bone marrow this is pretty much diagnostic for leukemia especially acute myelogenous leukemia the other thing that you may see is that when you look

at this on a peripheral blood smear or you look at this underneath a bone marrow biopsy and you actually take a look at it you may be able to see these kind of like little pink things here these are called Owl rods these are called our rods and our rods are very suggestive of AML but they're more suggestive of APL which is the subtype of AML it's actually just kind of like a polymerized crystallization of what's called myeloperoxidase enzymes okay so you may see our rods here or you may see our rods here and this

is again very suggestive of AML with this specific subtype called APL CBC with peripheral blood smear supported the reason we would have acute leukemia bone marrow biopsy definitely diagnoses and confirms acute myelogenous leukemia but then the next steps are really determining prognostication and treatment in other words they determine if a patient has a very specific sub type of AML what was that one that I keep stressing on Non-Stop APL that's what I want to know the first test that we can do is something called immuno phenotyping these aren't as helpful as the genetic studies in

this disease but what they'll look for is they'll support again the reason of AML and so immuno phenotyping we would have a very specific protein that would be positive you see this kind of like thing right here this is called myeloperoxidase and if the myeloperoxidase enzyme is positive or present this is supportive of AML that's very supportive of AML because there's another molecule that's actually seen particularly only in all and that's called tdt so it would be tdt negative in AML and mpo positive in AML that's really important flow cytometry is not helpful so I'm

just going to put that it's not applicable it actually doesn't provide any truly clinical useful information it's way more helpful in all okay so we'll talk about that when we get into all let's move on to genetic studies though genetic studies are actually very helpful and so what we can do here is I could take the nuclear material from this myeloblast and I can look at the actual chromosomes and I could try to find where is there an abnormal chromosome so I could do like a karyotyping basically and when I look and I'll see is

like oh shoot look there's this weird like swapping of genetic material on chromosomes 15 and 17. there's this weird translocation present if this is present this is suggestive of APL this is really important you want to know why APL which is a subtype of AML is a completely different treatment regimen that's why I need to know this so the purpose of genetic studies is not necessarily to diagnose AML is to find the specific subtype of AML which determines what type of treatments we will institute okay so this is really really important if I do this

genetic studies when I do cytogenetics and I find a chromosomal translocation 1517 is suggestive of APL that's important the next thing is I can do I can do like a PCR and what I can do is I can take and say okay here's my 15 17 translocation that I have I'm going to take the particular Fusion Gene and I'm going to look oh here's my Fusion Gene right here my Fusion Gene if I go out and I actually PCR and I actually try to find the specific Gene if it comes back positive for PML retinoic

acid receptor Alpha Gene it's positive for this this is highly suggestive of APL and again that's important because if I find this my friends this is going to determine a completely different type of treatment regimen that I would do for APL in comparison to all other subtypes of AML okay CBC with peripheral blood smear to start off the diagnosis of acute myelogenous leukemia bone marrow biopsy to confirm immunohistochemistry would give us potentially the mpo positive suggestive AML flow cytometry not super helpful in this one better for all and then genetic studies confirming the subtype of

AML called APL and which is important for treatment processes you can also test for some of the complications that we talked about leucostase is not as much um that would be a little bit more of a clinical diagnosis tumor lysosome you actually can test for and so what you're looking for is you're looking for all the evidence of those particular molecules that ruptured out of the cells to be present and so we actually the way I remember this is puke I know it sounds really weird but the cells are puking out their interest other contents

so there's going to be high levels of phosphates those will be high levels of uric acid they'll be so then you get to the the puke part right you got K you also have high levels of potassium so then you get to this weird one which is the okay we got the puke part you can actually remember that their calcium is low okay so the calcium should be low and the reason why the calcium is low is because it's complexing with the phosphates but if you guys remember what was the downstream negativity of the high

uric acid and the calcium phosphates they form crystals and these potential crystals that you can get plus this plus the calcium they can make these crystals and these crystals are the problem because they go and they get stuck where they get stuck son of a gun they get stuck in the kidneys and when they get stuck in the kidneys they cause a lot of acute kidney injury and when they cause acute kidney injury this may be evidenced by what a very high creatinine or a very high bun so these may be other things to think

about is potentially getting a electrolyte panel getting all of these electrolytes tested and also testing for any kinds of evidence of acute kidney injury the other thing is the DIC this is another scary one leukemia cutus and the ginger hyperplasia those are visibly evident but the DIC is another one that we have to be able to find and generally what we look at is the coagulation parameters so we look at things like the PTT we look at things like the INR we look at things like fibrinogen we look at things like d dimer we look

at things like platelets and we look at things like your red blood cells and this will kind of give us a good idea if a patient is in DIC and so what you'll see is that they're very bleedy bleedy and so because that usually whenever they have a high risk of bleeding the PTT and the INR will be elevated the fibranogen which was getting destroyed by the TPA is going to be in the dump the d diamond which is evidence of these fiber and degradation products there's lots of fibrinolysis D-dimer always goes up and then

platelets will also be getting consumed red blood cells will begin to consumed and also broken apart so these are the problems with this particular disease and this will help you to assess for and DIC so this would be for tumor lysis syndrome this will be for DIC and again leukemia acutis and the gingival hyperplasia is a physical examination finding and leukosases is technically a clinical examination finding as well or a clinical finding as well all right guys so now we're going to talk about treatment of AML now when we have a patient who has AML

the first thing that you have to remember is this is a disease that's primarily treated with chemotherapy okay so that's the primary thing that we're going to talk about so first thing is let's talk about AML specifically so the treatment of AML but specifically the non -apl subtype in this particular phenotype of AML the primary treatment is going to be chemotherapy all right so that's what I want you to remember chemotherapy is going to be the primary treatment process for these particular patients and the way we do chemotherapy for this patient population who has AML

of the non-apl subtype is we do it in a very specific way you actually do what's called induction chemotherapy then you do what's called consolidation chemotherapy for a certain amount of time and then you do what's called maintenance chemotherapy with the goal of being complete remission that's obviously the goal now the question probably comes is is what are the agents that are used to treat AML what are the chemotherapeutic agents and there's two preferable agents that are utilized one is called what's called a cytarabine so cytarabine is one particular agent and the other one is

called Ida rubison or its sister Donna rubison so you can do what's called Ida or Donna rubison these are the two particular options of chemotherapeutic agents that you would utilize for induction consolidation and potentially maintenance chemotherapy with the goal being hopefully complete remission all right that's the goal now if for some particular reason there's a very specific type okay so now we're going to talk about this next one here which is called APL so we're going to talk about the specific kind of like chemotherapeutic regimen that you can utilize in patients who have APL so

we're going to talk about the chemo therapy particularly in another specific type which is going to be the AML with the APL subtype in this particular population right this is a completely different treatment regimen so we use cytaribine eitheribusinodana rubicin for patients who have the AML subtype who have AML without not the APL subtype and we'll do induction chemotherapy consolidation chemotherapy maintenance chemotherapy with the goal of complete remission for this one this actually has a very favorable prognosis and so for this one we actually don't do this induction and consolidation and maintenance therapy we actually

can use something and what we're trying to do is the goal here is to promote differentiation so you're literally trying to take these myoblasts differentiate them into promyocytes and differentiate them into white blood cells like literally like turn them back into neutrophils eosinophils and basophils that's what you're trying to do so you're trying to literally take them to go from a myeloblast this is literally what you're trying to do you're going to give them something that caused them to go from a mild blast to a pro myelocyte to a granulocyte that is literally the goal

here and that might sound super weird because you're like why can't we do that with these this is one of the rare types of diseases that we can actually do this one and so that's what we want to do we actually want to try to stimulate this process to promote differentiation now the problem with this this can produce a really rare situation called differentiation syndrome we're not going to talk about that's beyond the scope of this lecture but the agents that we use to promote differentiation here are very cool so one is called All Trans

retinoic acid that's the first one this is high yield I can't stress this enough and then generally the add-on is what's called arsenic you're like arsenic sounds terrible is not good obviously but these are the two preferable agents to give to these patients and what you're trying to do with all trans retinoic acid and arsenic trioxide is you are trying to promote this particular process to be able to get rid of the my list because you've got tons of mild blasts start shunting them over to making granulocytes because now you have functional white blood cells

you don't have a lot of these mild blasts crowding out the bone marrow and causing all these complications pretty cool right if they do you can make massive amounts of granial sites this can produce produce something called differentiation syndrome where they have this massive cytokine storm and it can cause high mortality so usually with that situation we may add on steroids to this particular treatment regimen all right so this is the two chemotherapeutic options the options that the next com is is we can consider something called a bone marrow transplant and generally with a bone

marrow transplant this could be AML that's undergone so this is usually someone with AML and they have potentially two two particular situations they have AML with a very very poor prognostic type of AML so there's an AML with a pore prognostic findings so whenever we did the genetic studies if we found a very poor prognostic genetic mutation that was causing ml they're likely going to require bone marrow transplant because they're likely going to fail chemotherapy or if they have AML and they failed chemotherapy so they did not undergo complete remission from the induction consolidation and

maintenance therapy then we would go to a bone marrow transplant essentially what you're trying to do is create another hemocytoplast that's what you're trying to do you're trying to give them a hemocytoplast that will kind of be a better hemocytoplast and turn into proper myelow stem cells proper myelocity blasts and all the other types of white blood cells so you're trying to give them a bone stem cell that literally will actually take over and help them to produce functional white blood cells red blood cells all the other cell lines the next situation that I want

you guys to think about with AML is the treatment of complications and this is really what was the the big one so management of complications is the last thing that I want to talk about DIC that's I think that's kind of a little bit beyond this lecture uh it's specifically associated with APL so obviously treating APL with all trans retinoic acid and arsenic trioxide is of most importance the two particular complications that I need you guys to be aware of here is going to be leukostasis so leukostasis which is very high association with AML I

want you guys to think about leucostasis way more with AML than all and the other one is called tumor lysis syndrome and again what is this commonly associated with it's commonly associated with the chemotherapy you can't have it spontaneously but not as common leucostasis with the features of having more than a hundred thousand white blood cells are myeloblast technically clogging up the arteries of the brain clogging up the arteries of the lungs clogging up the arteries of the penis I'm sorry well technically the veins of the penis and clogging up the arteries of the retinal

artery causing things like headaches Tia cvas this neon hypoxemia acute respiratory failure causing blurry vision or vision loss and then potentially priapism or you know the problem whether the Venus of drains aren't uh properly draining things properly but in this situation there's too many white blood cells so in this situation you need to do something called cytal reduction so when this happens whenever a patient has leukostasis the big goal is cyto reduction and you have to do this quickly and the two ways that we can do this is one as you can start off with

what's called hydroxyurea and what hydroxyurea will do is it'll kind of like just knock down these actual myoblasts from continuously proliferating so it'll knock down the number of Mile blasts and then the other thing is we can actually suck some of those myoblasts out of the bloodstream so if we get rid of the ton of these mild blasts they won't clog up these blood vessels so get rid of tons and tons of myoblasts how do we do that we call this leukopheresis so Luca phoresis and this is technically going to be the best this is

I'd say the big high yield thing to take away this is the big one that I want you to remember okay so leukopheresis would be the way that we would help to be able to rip off all of these myoblasts and we would use hydroxyurea to also kind of shut down and knock down some of those mild blasts and then what we would do is we would transition and this is a strong indication for transitioning these patients into chemotherapy which we talked about above which would be the idea ardana rubison Plus cytarabine building is tumor

license syndrome what do we say was the problem with human lysis syndrome the problem with tumor lysosome is the high uric acid so remember what I want you to remember is uh here's a cell here's a myeloblast it ruptures out and Spills out uric acid now the problem is is actually let's go back a second because what does uric acid come from that's really the next important thing uric acid comes from something called purines so it actually it spills out something called purines purines they get converted into what's called uric acid and uric acid is

the thing that causes kidney damage so what I can do is when I have a patient with tumor license it's really kind of avoiding the Uric acids because that uric acid is what causes the to get kind of go over here to the kidneys and cause nephrotoxicity so it's really this uric acid molecule that's getting deposited to the kidneys that's causing acute kidney injury the whole goal of treating tumor lysosome is trying to avoid acute kidney injury so what I can do is I can give one drug and this drug is going to inhibit the

conversion of purines into uric acid this drug is called aloe paranol so that's one drug I can give the second thing is what if a lot of these peerings that I spilled out already got converted into uric acid allopurinol will help to stop it if it hasn't converted yet but what if I already have a lot of uric acid that's already been formed already and allopurinol is not going to be as effective well I'm gonna end up with a cute kidney injury so how do I avoid this I make him less toxic so I convert

them into something called Allen Towing and allotone is this is toxic this is nephrotoxic this is not toxic to the kidneys so the question is how do I give a drug that helps to stimulate this pathway this is called raspberry case this is called Razz beer case so raspberry case will help to be able to convert uric acid into Alan tone so I end up with less uric acid and less risk of acute kidney injury pretty cool right so that's the ways that I would do this allopurinol and raspberry case and then also keep these

things flushing through the kidneys so keep them properly hydrated so that the crystals don't have time to be able to precipitate and so the other thing I can do here is I can do Allopurinol I can do raspberry case and the other thing that I should give is to keep them kidneys continuously flushing out those crystals IV fluids so IV fluids would also be preferable as well other things that you could do is again you can also bind up some of the phosphates we said you can give things like sevalamir you can also give things

that can actually help to avoid the potassium kind of rising so you can give things like insulin D50 you can also give things like a albuterol treatment and things of that effect but I think this is the more important thing to take away from treating tumor lysosome is keeping the kidney skin properly hydrated and flushing out the crystals and avoiding Crystal formation all right my friends in this video we talk about acute myelogenous leukemia AML I hope it made sense I hope that you guys enjoyed it as always until next time [Music]