Acute Lymphoblastic Leukemia (ALL)

foreign what's up Ninja nerds in this video today we're going to be talking about acute lymphoblastic leukemia also known as all before we get started if you guys really do like this video it makes sense to you please support us and I really mean this one of the easiest ways that you guys can go about supporting us for these free videos is by hitting that like button commenting down the comment section and please subscribe it really goes a long way also I really urge you guys if you guys have the opportunity and the ability to

go down in the description box below go to our website we have some amazing notes and illustrations that I truly do believe will help you guys to understand this topic and follow along with me as we go through this together but let's get into talking about all so with all or a q lymphoblastic leukemia the problem is within hematopoiesis so what is hematopoies this is the production of all blood cells and really this should occur in the red bone marrow right so all we're doing here is that we're taking a chunk of this actual bone

marrow and we're just zooming in on it looking at all the actual cellular division that's occurring there and then we have to talk about a little bit so if you guys remember from our videos that we've talked about this before we have a kind of like a stem cell that generates all blood cells you guys remember what this is called some people call the pluripotent stem cell some also call it a hemocyto blast happens is it differentiates it differentially what's called a lymphoid stem cell and a myeloid stem cell and if you guys remember from

the AML video the myeloid stem cell will then actually differentiate in the presence of something called like erythropoietin it'll go into making what's called red blood cells then if it has the presence of what's called TPO or thrombopoietin it'll go to make platelets and then if it has the presence of like Colony stimulating factors it'll then go to become what's called a myeloblast and then myeloblast in the presence of other colony stimulating factors and interleukins will then go to become something called a granulocyte and there's different types of granulocytes if you guys remember this is

your neutrophils your eosinophils and your basophils so this was the process of hematopoiesis down this cell line but down this one it's a little bit different right so we have this lymphoid stem cell can become a generic type of blast we call this a lymphoblast now what can happen is that the lymphoblast can differentiate you just a little bit further and when they differentiate a little bit further they become something called a b lymphoblast so you can have what's called a b here I'm actually going to write this one over here so we can have

two different types of lymphoblasts if you will one is called the B lympho blast and the other one is called the T lympho blast and these are just two different types of just slightly further differentiated lymphoblasts but then what happens is is that these lymphoblasts the B lymphoblast and the T lymphoblast they should differentiate a little bit further in a true perfect kind of like world and how do they differentiate they differentiate completely into something called T cells and B cells or we can call them T lymphocytes and B lymphocytes so what these really should

become eventually is that these should become T cells and these should become B cells are also known as B lymphocytes and T lymphocytes and technically the T cells they should further go and differentiate and become a little bit more specialized in the thymus so these are the only ones that will go to the thymus whereas the B cells these will generally go to the lymph nodes and we'll talk about this a little bit later so the B cells generally go to the lymph nodes and the T cells go to the thymus and some will go

to the lymph nodes but we'll talk about these a little bit later but the problem really comes in discussing this is what is the true breakdown in the somatopoiesis process so we said all is a breakdown within the amount of police's pathway and really what happens is it's just similar to like AML is that in all there's a problem where the lymphoblasts become just a little bit more differentiated and they become these things called B lymphoblasts and T lymphoblasts right and what happens is they get stuck right here they get stuck right here and they

can't further divide and differentiate to become functional T cells and functional B cells so you end up with decreased functional B cells and functional T cells and you end up with a ton of these T lymphoblasts and B lymphoblasts and that's where the where the problem really comes in is that there is a problem where these cells are stuck in this division stage of continuing to form more and more and more lymphoblasts without fully differentiating and making functional B lymphocytes and T lymphocytes so the question then comes into the next part of this lecture which

is what would be the reasons why that we would have so many of these T lymphoblasts what would be the reason why we would have so many of these B lymphoblasts actually if you guys remember here was our hemo cyto blast becoming our myeloid stem cell becoming our lymphoid stem cell then this one went down and became all these different cell lines that we already talked about let's focus on this one here we have the T lymphoblast here we have the B lymphoblast and it just does not become a B cell and it does not

become a T Cell so it's stuck in this stage where it just continues to keep replicating and dividing without ever dying and having tons of these dang lymphoblasts and less functional T cells and B cells so what's the reason why it's stuck in this all right one reason is it could be due to chemo radiation just as we talked about this in the lecture on AML the chemo radiation may cause DNA mutations so there may be some type of mutation right so you have the DNA here's your DNA and then here's maybe a gene that

has now gained the capacity to continue to replicate without the cell dying this Gene is now mutated from the chemo radiation when it mutates in this particular way maybe it then gains the ability and the capacity to continue to keep replicating and so the DNA replications go haywire and if you have tons of DNA replication without the cell actually dying that's how you end up with these massive amounts of T lymphoblasts and B lymphoblast without actually completely fully becoming a differentiated T Cell on B cell so that's one reason the second reason is it actually

can be genetic let's actually bring these up here so genetic etiologies is another possibility here so when I say genetic there is some type of predisposition and there is three particular reasons one is it could be associated with what's called Down syndrome and we talked about this prior in the AML lecture so you can see Down syndrome associated with AML and all and this is also known as trisomy 21 so Trisomy 21. the other particular chromosomal abnormality is that you form a fusion Gene and this is usually due to two different types of translocation so

there's a trans location we talked about this one and the AML lecture was the most important one was 1517 for APL the translocations in all there's two particular ones one is called the 1221 translocation and this one what happens is it's the same kind of concept here here you have let's say a chromosome 12 here you have chromosome 21 and what you do is you just swap some of the genetic material and you make this like weird Fusion Gene and when you make this weird Fusion Gene this Fusion Gene gains the capacity to continue to

keep replicating and dividing without dying and that's how you end up with these massive amounts of these T lymphoblasts and B lymphoblasts the other concept is that it could be due to another translocation and this is really important one my friends 9 22 translocation and this concept you again have chromosome 9 chromosome 22 and you're just swapping some of the genetic material and you make a very very important Fusion Gene so we call this the Philadelphia I'm going to put Philadelphia chromosome and what happens is you make this weird Fusion Gene here was the fusion

Gene here here's the fusion Gene here and this one's actually really important we call this a BCR able Gene and this is really important for 922 translocations but again the same concept exists here where these Fusion genes gain the capacity to continue to allow for excessive amounts of DNA replication without the actual cell dying so becoming mortal essentially now one big thing here is that 1221 translocation is common in children which makes this an unfortunate and sad situation 922 translocations are more commonly associated with adults so it's less common the more common translocation that is

commonly seen in all is the 1221 translocation so if you have to remember which one is more common please remember that this is the more common one however it is important to be able to determine if they have this one the reason why is is there's a different treatment for this particular translocation and this particular Gene that's present it's a different treatment regimen okay the third and final reason that someone can develop all is a weird one and it's more specific to the T-cell all and this is usually due to an infection so there's an

infection a specific type of virus it's called the human T lymphotropic Virus so we call this the htlv virus so the human T Cell lymphotropic virus this one is primarily only associated with T cell all so there's two different types of all if you really want to think about it you can have an all where it's primarily the B lymphoblast and the T lymphoblasts that are the problem which one would be the more common one if I actually had to pick between these these B lymphoblasts and the T lymphoblasts this one is about 20 percent

of alls and this one is about 80 percent of alls so therefore when someone has all which is the more likely cell line to be affected the B cells so you're likely to see a B cell all more than you'll see a T Cell all but if you do see this one what's the one particular thing that you have to think about htlv okay so I'll add this one on here as well as an important kind of high yield thing to take away all right my friends so now we've covered at this point the abnormal

hematopoiesis pathway and we covered the reasons why we have tons of these B lymphoblasts and T lymphoblasts now let's talk about the consequences of these now all right my friends so now we got all these tea lymphoblasts and B lymphoblasts just populating like bunnies within this dang bone marrow right and what was the reason why again it could be due to chemo radiation causing mutations or it could be the genetic abnormalities associated with like trisomy 21 Down syndrome but you can see in AML and all and don't forget the translocations that cause weird Fusion genes

that cause excessive DNA replication and again these cells can divide divide divide without dying they evade apoptosis they become immortal and then the last one is you could have a T Cell all associated with human T Cell lymphotropic virus and again which one of the more common one B cell a allows 80 T Cell all is 20 so it's way more common to see and all with a B lymphocyte predominance okay we got all these lymphoblasts that are just populating in the bone marrow and they crowd out the bone marrow and they cause a lot

of problems so what are some of these problems well one thing is let's see all these cell lines so because you have these massive amounts of lymphoblasts these are going to be super high because you're just continuing to replicate and divide these without them differentiating maturing into true T cells and B cells and because of that you're taking up so much space in the bone marrow and you're hogging all the nutrients that is needed for red blood cell production and platelet production so now and these cell lines become affected and they drop what is the

reason why these cell lines drop because there is decreased space and decreased nutrients available for them to continue to undergo their production process so you drop these other cell lines when we have all these lymphoblasts in the bloodstream one of the problems is that these have a decrease their decreased functional white blood cells so you have these decreased functional white blood cells they aren't able to perform their normal functions which is fight off particular types of pathogens release cytokines promote an inflammatory reaction and fight off infections if I can't do that that's a problem so

now I'm going to lose the ability of these poor things to be able to perform their natural functions and so that's a downside to this one and so one of the big things that you want to remember is that now you have less functional white blood cells this is going to lead to a high risk of infections and infections for these patients tend to be one of the higher mortality causes of death so this is this produces the high mortality factor which is associated with leukemia now one of the ways that this can present is

they can present with pneumonia they could present with a UTI they could present with some type of cellulitis or abscess of the skin and so this is various different ways that the patient may present but again I think the big thing to remember is because you have less functional white blood cells there is a higher risk of infections associated with this the other component here is that you drop down your number of red blood cells and because you drop down your number of red blood cells you actually can cause anemia now anemia would be evident

if you got a CBC and showed that there was low numbers of red blood cells but one of the ways that these patients can present is they can present with power due to a decreased Hue to their skin you know red blood cells if they're oxygenated properly have enough of them they should give a nice like pinkish reddish shoe to the skin but if you don't have enough of them then you're not going to have that nice pinkish reddish Hue and they develop a pallor they're also supposed to supply oxygen to tissues that help us

to be able to perform normal functions give us energy we lose that then we become fatigued and on top of that you can develop dyspnea because of less oxygen carrying capacity now that's one particular feature that we could also see here associated with this now the other component is that we have less platelets because of that space problem so because that we call this thrombo cytopenia and the problem with thrombocytopenia is that yes you could see this on the CVC showing low levels of platelets but they could physically present with plates they're supposed to do

what supposed to clog up holes in blood vessels if they're broken or ripped up and if you can't do that now now you'll bleed through those holes and you can develop little bruisings on the skin which we can call petiki eye you can see bigger ones like pepera you can see even bigger ones in that like echymosis or you could literally bleed like you get a nosebleed you could get gingival bleeding you could bleed through your git so it's important to realize and look for features of bruising which can kind of present as fatigue eye

you could present as purpura could present as ecchymosis or you could present with evidence of bleeding epistaxis gingival bleeding or GI bleeding so watch out for this as well as potential features and complications associated with this problem of high lymphoblasts the last particular problem is is that since you have so many lymphoblasts within the blood within the bone marrow there's so many lymphoblasts that are just constantly replicating like bunnies in the bone marrow what's the problem with that well now if you have all these lymphoblasts and the bone marrow and you're making a ton of

them now the bone marrow has to be able to compensate and expand and make space for all these lymphoblasts so what happens is you end up expanding the bone marrow and when you expand the bone marrow you actually cause kind of a distension and activation of pain receptors and nerves and this will precipitate a bone type of pain which may present with the child limping and so watch out for maybe a limp or them complaining of particular bone pain in their areas where red bone marrow is actually present these are the big features that I

want you guys to watch out for which is associated with lots and lots of lymphoblasts within the bone marrow here's the next part though the next complication is that we know that b lymphoblasts and t lymphoblasts are made particularly within the bone marrow but then what happens is as we said prior is that these should get pushed into the bloodstream when they get pushed into the bloodstream they're supposed to go to specific areas of the body some will go to the lymph nodes some will go to the thymus some will go to the liver in

the spleen and some will go to other locations that we don't want them to go what would that look like so if some of these lymphocytes went to the liver in the spleen ah these poor things what happens is it actually causes the liver so now you're going to deposit all these lymphoblasts into the liver and into the spleen and what you end up with is something called hepato spleno megaly a big old liver and big old spleen and one of the problems with hepatosplant Omega is this can present with like nausea vomiting because if

you imagine the liver and the spleen getting bigger it's taking up a lot of space within the git and it can compress onto the stomach and onto the bowels and so when food is supposed to go through they're supposed to go through there without any kind of compression or kind of like restriction but now if you have things compressing onto the git organs like your stomach and bowels you're not going to be able to push food along easily and so that causes a lot of nausea vomiting abdominal fullness so watch out for that as well

so nausea vomiting and abdominal fullness this is a big thing to watch out for okay so hepatosplenomegaly is relatively common with this one the next one that I want you to remember and I think this is probably the biggest one to remember is that they can deposit into lymph nodes so B cells and T cells naturally go into lymph nodes and when they deposit into the lymph nodes and you get tons and tons and tons of these they can cause something called lymph adenopathy lymphadenopathy and this is probably one of the most common features that

you can see with any type of lymphocyte predominant type of Leukemia and you may see these within the cervical region or other areas around the body so really really watch out for this one the other one is that some of these actual lymphoblasts get deposited into the meninges oh this is a really really sad one and this is really really unique and really important to differentiate between AML and all if they did they kind of deposit into the meninges this can lead to something called meningeal leukemia meningeal leukemia so they can literally they can present

like they have meningitis and so watch out for features of meningitis so headache photophobia phonophobia you know nausea vomiting maybe focal neural deficits these are really really in big altered mental status these are really really important things to watch out for the other thing is that there's a lot of cranial nerves that move through and around the areas of the meninges especially the sixth cranial nerve and so when you get a lot of like deposition into the meninges and kind of compressing onto the six cranial nerve you can get a cranial nerve palsy so also

watch out for not just meningeal leukemia but also watch out for what's called cranial nerve palsies with the most common one being six nerve palsy six nerve palsy so watch out for any issues there so if your six nerve isn't able to work you can't abduct the eye okay so watch whenever you perform their actual extra ocular movements if they're unable to abduct the eye that could be a potential indication of this as well all right so so far we have been depositing into the liver and the spin causing big swelling of that one lymphanopathy

this would not generally be a painful one this would generally be kind of like a large non-painful non-tender type of swollen lymph node meningo leukemia they can literally present with features of meningitis or a cranial nerve palsy specifically six nerve inability to abduct the eye the other problem here is that these son-of-a-gun lymphoblasts can also deposit into the testes and if they deposit into the testes which is a really unfortunate thing in these children it can cause testicular enlargement so watch out for any type of testicular enlargement which is a really really unfortunate thing it's

not as common as compared to the meningo leukemia but it is something that you have to be aware of that they can deposit into the testes and again I say some of the biggest biggest features that really help to differentiate this from AML is the effect that they have lymphadenopathy and meningeal and testicular involvement you can see rarely splenomegaly with AML but it is it's not that common I really would rather you remember hepatible and omegaly more common seen in a ll than an AML okay here's the other really interesting thing that helps us to

further differentiate AML from all based upon pathophysiological presentation now if you guys remember the thymus sits on the heart right here kind of like sits like right here I'm going to draw this one in green so it sits and overlies on top of the heart what did what kind of cells what kind of cells specifically which ones deposit into the thymus together so this is our thymus here here's our thymus which specific types of lymphoblasts deposit into the thymus I only mentioned one the T cells so if you get lots of tea lymphoblasts that are

large and in charge and all mad you know all coming over here and depositing into the thymus the thymus will get larger when the thymus gets larger so you cause what's called thymic enlargement this can lead to a couple different types of problematic issues well think about the things that it's compressing it's big enough that it can compress on the trachea or bronchi so if it compresses on the tracheum bronchi so you get tracheal and bronchial compressions over trachea and it can also compress this one right here so it can compress here and here compress

the trachea and it can compress the esophagus so it can compress the esophagus now another potential issue that you can also see is that it can also compress this structure here so you see how you have this vein it's supposed to come down right here so you have what's called your brachiocephal you're supposed to have what's called this one right here so you have your subclavian IJ making the brachiocephalic and it'll come down right here and join and become the superior vena cava this thymus could compress onto the superior vena cava as well so we

could compress three particular structures here we can compress the trachea which can lead to dyspnea and Strider we can compress the esophagus which leads to dysphagia and we can compress the SVC which can cause SVC syndrome and this could present with a lot of like swelling like really enlarged neck veins or maybe a lot of like enlargement of the veins on the actual chest in the face and the arms maybe a bluish kind of discoloration as well so that's a real big thing to take away from here is that you can get thymic enlargement due

to the teeth lymphoblast depositing this is really important you would only see this only see this one in T Cell all you can see all of these in either b or T Cell but you will only see this thymic enlargement and T Cell all and if they cause Islamic enlargement they can compress the trachea they can compress the esophagus and they can compress the superior vena cava which may cause these particular types of clinical presentations okay these are the real big things that I think help us to delineate AML from all based upon pathophysiological presentation

there is two other things that can present I'm only going to write them down because we already harped on them in the actual electron AML but there's two other presentations one other presentation that you may potentially see is leukostasis so you may see leukostasis but I want you to remember that this is way more common in AML than it is in Alo so that is another potential presentation remember what they get tons and tons of these actual blast cells they get stuck within the bloodstream and they occlude the blood flow to the bloodstream and they

can cause Strokes tias right they can cause headaches they can cause a blockage of the pulmonary vessels causing hypoxemia and dyspnea they can block the retinal vessels and cause vision changes or vision loss and they can even block off the drainage veins of the penis and cause priapism so that's all potentially seen as well as in AOL but it is more common I'd rather you associate this with AML and the last one that you can also see is tumor lysis syndrome and we talked about this one this is whenever the cells either you have a

high tumor burden so massive massive amounts of white blood cells over these case the lymphoblasts that are actually present and getting stuck in capillaries and popping open or they're getting chemotherapy and it's busting the cells open and they're releasing potassium and phosphates and uric acid and you can get an acute kidney injury associated with that so again you can also see tumor lysis syndrome and leucostasis which we talked about which is present in AML and all so you can see this in AML and all but these are the new things that I want you guys

to remember if you guys already watched our video on AML these are the new types of presentations but leukostasis and tumor lysosome are also potential presentations that you can see in all but I want you to remember leukostasis more common in AML and tumor license center we'll discuss this a little bit further in treatment is usually a complication of chemotherapy but we've already talked about this in AML now let's move on at this point we've come to the consideration that if a patient has all we know that it's usually due to a problem with the

lymph lymphoblast the b or T Cell line we now know that they can present with potential alterations of blood cell lines we also know they can actually cause deposition and problems in multiple different organ systems and then potentially complications such as these that we've discussed now what we need to do is move on to how do we diagnose it when this happens you start off with the CBC with the peripheral blood sprayers kind of your general screening test now what this will do is it'll tell us the effect that we had from all those lymphocytes

that are in the bone marrow they're crowding out the bone marrow taking up space what were the cell lines to be affected what happened to the red blood cell line it will drop what will happen to the platelet line it will drop and so because of that what do we call this when we have low red blood cells we may see low red blood cells as evidence of anemia on the CBC we may see low levels of platelets or thrombocytopenia on the CBC and that is again secondary too low space the lymphoblasts crowding out the

bone marrow now the question is what about the actual mature white blood cells what happens to these These are variable I'm not even kidding you can't like diagnostically rely on these they could be high they could be low so you can have a lot of variability in your functional white blood cells so these could be variable so I just want you to remember that that's not a reliable marker sometimes you may have leukopenia sometimes you may have leukocytosis but what's the most important part the most important part is that you should have tons and tons

and tons of lymphoblasts that's really the big feature not know as much the functional white blood cells it's more the lymphoblast yes they are a white blood cell but they're not fully functional and so when you look at these what you should see is tons and tons of lymphoblasts and what we would find is if I were to take a section of blood if I took some blood out of a tube and if I were to take all of that blood and put it on a slide I theoretically if there's tons of these lymphoblasts there

should be a strong chance I will see a good chunk of lymphoblast on that slide from that blood that I took from you and so what we would want to see is is on a peripheral blood smear I would want to see evidence of these particular cells called lympho blasts and if there is evidence of these immature lymphoblasts that are present on the blood smear that's also indicative of all okay the reason why is you might be like oh well what about AML well AML yes it did have low red cell line it did have

low platelets it did have variable white blood cells but what kind of cells did it have on the peripheral blood smear myeloblast with the owl rods these will have specifically lymphoblasts no eye rods that's a really big Telltale sign all right you're like I'm not convinced I'm still not convinced that it's definitely a Halo all right unfortunately what we may have to do is a definitive diagnostic test so definitively diagnose this definitive diagnosis is we will take a chunk of the bone marrow out so when we take a chunk of the actual bone marrow out

in this I did not spell definitive right let me actually respell this one here definitive Definitive I'm terrible speller apologize guys so definitive diagnosis what I would want to do is is I want to take a chunk of the actual bone marrow when I take the chunk of the bone marrow out what I should see is what I talked about before I should see massive massive massive amounts of lymphoblasts present within the bone marrow crowding out the bone marrow dropping all the other cell lines so when I look here what I should see is I

should see greater than 20 percent lymphoblasts that are present in the bone marrow so I should see a Super Hyper cellular bone marrow with that primary cellular component being lymphoblasts if I see this this is highly highly diagnostic of a patient having all so at this point if I start off with a CBC with the peripheral blood smear and it looked like this is definitely a possibility of all you need to go to the bone marrow biopsy to definitively diagnose it and say oh dang there is a lot of lymphoblasts here once I've done this

I have diagnosed all but what I really want to be careful of is in AML we diagnosed the same thing AML off of cbco peripheral blood smear and Obama biopsy but then we went on to do something called immunophenotyping and genetic studies and the reason why we did that is to determine the subtype of AML and the same kind of concept there is no specific subtype of all well there is if you really want to think about there's T Cell all and B cell all so technically we can say there's a subtype but we also

want to know is this a specific type of chromosomal abnormality like a 922 because that's a different treatment process just like in AML we wanted to know if there was the 1517 translocation because that was a different treatment process same kind of concept so we have to do immuno phenotyping in genetic studies to help us out with our treatment and our prognostication so when I do immuno phenotyping what I want to know is first thing is immunohistochemistry is there a specific type of like molecule that's present in this lymphoblast that is not seen in myeloid

stem cells or in the myeloblasts do you guys remember that in this you're going to have a very specific type of molecule called tdt right so in these lymphoblasts and having these lymphoblasts one of the particular types of molecules that is a Telltale sign is they will be tdt positive and they will be what's called mpo negative please tell me you remember what MPL was myeloperoxidase that was only seen in myeloblasts there's one Telltale sign so if we have a ton of these lymphoblasts and we check for a specific type of protein that is present

only only in the lymphoblast and not present in the myeloblast this is what we should see so that's testing for specific protein inside of the cell now we want to do is test for specific proteins on the outside of the cell and how will I do that well what I want to know is what kind of CD proteins or cluster differentiation proteins are present on the outside of the cell because the type of cluster differentiation the CD proteins determines if it's a T cell or a B cell oh that's actually really helpful so now I

can actually use this to know is it a t lymphoblast telling me that this is a t a l l or is this a b lymphoblast telling me that this is a b a l l with knowing the percent likelihood is that it's likely the B cell right 80 bll B cell all now what I want to do is is I want to find out what are the specific types of proteins that are present on the outside of these cells so what we do is we take these cells and we put them in a column

and we run them through the column and put little antibodies that bind onto these proteins and they'll cause them to become fluorescent and light them up and so what I would want to know is is is the specific type of proteins that are present on this T lymphoblast and B lymphoblast what are they because that'll tell me which one it is so if I know I have a patient who has a l l I just want to know which one it is right so what I would do is I would run it through a column

and I'd put an antibody that would bind onto these things and then I would have this like little fluorescent molecule and it'll light it up and tell me oh this is specific for this specific particular type of protein so what are those particular proteins in t lymphoblast the specific CD molecules that they have is cd2 to cd8 with the most probably like significant one is CD3 being the most important one within that CD two to CD 8. so if you see CD3 or anything from cd2 to cd8 that's highly suggestive of the T lymphoblast type

so this would be t a l l all right so now with the B lymphoblasts they have another specific type of CD protein so on theirs when you actually tag these ones the specific tag will light up for CD 10 CD 19 and 20. so CD 10 19 and 20. now when these are present if you see these it's obviously B type of lymphoblasts and this is really really important so this is why flow cytometry is more beneficial for all do you remember it really wasn't helpful in AML it's because there's no specific cluster differentiation

proteins that really help to differentiate between the different types of AML most of them have the same cluster differentiation proteins but these have different types of cluster differentiated proteins which is helpful in identifying which type of lymphoblast is it and that is important so we've come through we've determined oh the specific protein in the cell is tdt not mpo that tells us it's not AML again we've already known that at this point but it can just confirm a little bit more we do flow cytometry to tell me is it T Cell all or B cell

all remember the low numbers is going to be the T Cell the high numbers are going to be the B cells all right at this point we now move into genetic studies and this is a really important one as well so what I want to do is I want to take the nuclear material and I want to string it out I want to look at the chromosomes and I want to find is there a specific chromosomal abnormality now we already know that there was the swapping of specific genetic material two types right there was a

swapping of genetic material two types there was a 12 21 translocation and a 9 22 translocation out of these which one was associated with children this was associated with children this one was associated with adults but the real important thing here is that 1221 is more common 922 is less common however with that being said when we yes we can find these particular types of translocations present one of the big things to be able to remember here is that with 922 translocations in this particular abnormality here this involves a very specific type of treatment process

so the treatment is different and that is crucial my friends so that's why we really want to be able to identify the 922 translocation of the Philadelphia chromosome because if we find that's present we will have to give them something called tyrosine kinase inhibitors whereas if it's this one it's a different it's a chemotherapy to graduate that we will kind of defer to a little bit more specifically now the last thing here is once we've done the cytogenetic portion which is finding the chromosomal abnormality we will then come down and maybe take it a little

bit further so if I take it a little bit further and I say okay I know that there was this 9 22 translocation that was present for the Philadelphia chromosome but I know that when they do this there's a specific Fusion Gene that's present and if that is present in combination with the 922 I know that's highly suggestive of a very specific type of abnormality that has a different treatment process what was this Fusion Gene it was called the BCR able if it is BCR able positive and on top of that a 922 translocation is

present this is important because this will involve the treatment with something called tkis these will be treated with what's called tkis tyrosine kinase Inhibitors and that is an important thing because what happens is the BCR able Gene just hyperactivates these tyrosine kinase proteins and causes excessive amounts of hyper stimulation and replication this is why this these lymphoblasts become immortal with that being said at this point now we've taken the genetic studies and we've said okay now the patient has all we've determined that they have all based upon the immune history chemistry we said okay I

know if it's T cell or B cell based upon the flow cytometry and then I said I can determine the chromosomal abnormality but the real one that I need to know here is is it 922 if that is present is there the BCR able if it is that's important because that determines the treatment with tyrosine kinase inhibitors now the last part here is that we have to talk about some tests for if the actual lymphoblasts are really really in high amounts they're getting into the bloodstream they're moving through the bloodstream and they're depositing into these

different tissues they're specific tests that we have to be able to recognize if they've deposit into different tissues so it's really straightforward if they deposited into the actual meninges so they deposit into the central nervous system what would it be good test to think about for that one I would want to get like a CT or MRI so a CT or MRI would be able to tell me if there is any features of meningitis so I would see it particularly enhance on particular sequences on MRI I also could consider a LP and an LP would

be positive for these specific types of lymphoblasts that are present within the actual subarachnoid space so I could do an LP or I could do a CT or MRI we also see a lot of testicular enlargement I could do a testicular ultrasound to be able to see is there a large kind of mass present within the actual again testes so if I wanted to do a testicular Mass to find that I would actually do a testicular ultrasound is what I should put to secular ultrasound so again you can do ctmri to look for enhancement of

the meninges on the Imaging and LP Define the high number of lymphoblasts that are present within the subarachnoid space testicular ultrasound to find the testicular enlargement so if there is thymic enlargement that's present right it's just pumping this sucker real big it can cause a lot of mediastinal widening and Mass Effect and so what you want to do is get a chest x-ray of the chest x-ray or a CT of the chest and this will be able to show that kind of like enlargement of the thymus and really enlargement of the mediastinum the last one

if there's a lot of this kind of like deposition into the actual liver and spleen you'd see a lot of hepatosphenomegaly and the apatosphonomegaly can actually be picked up with an abdominal ultrasound or it can be picked up with a CT scan of the abdomen so these are potential things to be able to consider as additional tests to support the features and complications we talked about about before so if a patient has meningitis right you'd really want to be able to diagnose that not just off physical exam findings but Imaging and lab testing testicular enlargement

find that with potential physical exam and palpation but also ultrasound to find the enlargement and then again a thymic mass you can have features of SVC syndrome tracheal compression lymphoid the Disney and Strider or dysphagia but find the mass that's compressing that and then again if they have kind of features of abdominal fullness or kind of a larger admin nausea vomiting anorexia find the hepatosphonomegaly based upon that as well all right my friends now let's talk about the treatment of all armor first so now we're going to treat the patient who has all so regardless

of it being kind of a ba uh b-cell all or T Cell all you kind of treat it relatively the same so we start off with something called something called the combination chemotherapy and so it's the same kind of concept we talked about in AML so we have to start them off with chemotherapy but there's two different types so there's what's called systemic chemotherapy that we'll start off with on these patients but then we have to do something else and this is called intrathecal chemotherapy and I'll talk about this in just a second but you

should understand that intrathecal is essentially you're putting things into the brain and that should make sense off right off the top of the Dome because we remember that patients get that meningeal leukemia so oftentimes if they we will treat them we'll actually do prophylactic treatment to prevent them from developing meningo leukemia but we have two different types of semichemotherapy and intrathenco chemotherapy so when we start off with these we do the same kind of concept as we did in AML we automatically initiate what's called induction chemotherapy so we do induction then we do consolidation and

then after that we do something called maintenance chemotherapy maintenance and the whole goal is to get these patients all the way into the point of complete remission sometimes that works sometimes that doesn't the agents that we utilize here and I don't think that this is something that you should focus a ton on but I'm going to put them there but again I wouldn't go too crazy having to spend too much time remembering this but the way that I remember them is called cvad so remember c v a and then two D's here so with these

the first one is cyclophosphamide so cyclo phosphide again when we do our pharmacology lecture on all the chemotherapeutic agents we'll go into this in more detail the next one is called vincristine the next one is called asparaginase asparaginase and this is a plus or minus so sometimes we utilize this and sometimes we don't the other one is called Donna rubison and the last one is called dexamethasone and this is a steroid so dexamethasone and this is a steroid these are the three particular these are the actual drug regimen that we would utilize and a patient

who has something like all and we would use these within the phases of induction consolidation and maintenance now once we've done this we do this with a goal of hopefully being able to induce remission so hopefully eradicating and causing the patient to become completely cancer free now what happens is because all has the possibility of spreading to the brain and causing meningeal leukemia which is a very very frightening type of thing we like to prophylactically treat them so how do we do that so what we'll do is we actually do a prophylactic treatment and we

will use two different ways of doing this one is we'll use chemotherapy and the other one is we'll use something called radio brain irradiation and this will actually be a plus or minus we can do cranial radiation plus or minus but the chemotherapeutic regimens that we would use is we use something called Methotrexate and we use something called cytarabine and we also can use something like steroids the most important one and the one that you'll likely see on your exam is going to be Methotrexate so but these are the three chemotherapeutic regimens that we will

utilize for intrathecal components so we could actually do this via lumbar drain and then push this medication into the subarachnoid space or we can do it via what's called like an EVD we put like the catheter into the actual ventricle and squirt this medication into the ventricles but either way you're trying to just get this into the subarachnoid space and trying to be able to prevent the meningeal leukemia from occurring so this is usually a prophylactic way another way that we can do this is we can do cranial irradiation therapy but this is usually a

plus or minus so we can do cranial plus or minus cranial irradiation after the chemotherapeutic regimen but this is at least what I would want you guys to remember this is a really important one with all they have a high risk of meningo leukemia you can treat them with systemic chemotherapy but you should prophylactically do intrathecal chemotherapy to prevent meningeal leukemia by giving them intrathecal Methotrexate if you can remember the other two great plus or minus brain irradiation therapy that is important now if these fail we have other Advanced therapies so there is other advanced

therapies and this gets into the other concept that we talked about and there's two particular Advanced therapies that you don't want you to remember one is going to be what's called tyrosine kinase Inhibitors and the other one is called a bone marrow transplant now in these two particular situations tyrosine kinase Inhibitors there's one specific agent that we would utilize here this is called a matinib a mat nib is the most common agent here we utilize this in patients who are positive for the 922 translocation and they are positive for the BCR able Gene if they

are positive for these particular things then they meet the criteria to be treated with tyrosine kinase Inhibitors such as a matinib now if these patients fail chemotherapy they fail chemo they fail the tyrosine kinase Inhibitors or they have a poor prognostic findings on their labs then we will go to a bone marrow transplant prognostics then we would go to a bone marrow transplant okay now this is the general treatment so to get a recap this we would treat them with induction consolidation maintenance chemotherapy with at least if you can remember them these particular agents such

as cycophosphamide been Christine as plus or minus asparagenase donorubicin as well as dexamethasone hopefully with the goal of remission we have to remember this one we have to prevent them from developing meningo leukemia so we intrathecally treat them with chemotherapeutic regimens into the subarachnoid space such as at least remember Methotrexate if you can remember cytarabine and steroids great also we may consider brain irradiation therapy to prevent this as well in advanced therapies we can do a bone marrow transplant if they've failed all treatment regimens with the chemotherapeutic regimens and the tyrosine kinase Inhibitors or if

they have a poor prognosis and then we can do tki's tires and kinase numbers like a matte nib if they're positive for that 922 or BCR able Gene the last thing is the complications and we briefly talked about this prior and the one complication that I really want you guys to remember here is the tumor lysis syndrome remember leucostasis is more common in AML not as common in AML all but if you do remember leukostasis it was hydroxyurea and leukopheresis and then get them to chemotherapy but complications here the most important one that I want

to remember is tumor lysis syndrome and if you guys remember it was the same kind of concept I just don't want you guys to forget this because it's a high yield topic if I take those cells here's my uh cells the leukemic cells and I hit them with the chemotherapy and they pop open they release out their different contents and the contents that they release out into the actual extracellular environment is phosphates they release potassium and they release uric acid and these are problematic molecules because what they do is this specifically will cause acute kidney

injury so how do we prevent them from developing all these uric acid crystals we treat them with what were the particular regimens we do one IV fluids second is we inhibit purines from converting into uric acid which was Allopurinol aloe puranol and then third if most of the uric acid has already been formed we bind up the uric acid and convert it into something else that's not nephrotoxic which was raspberry case Razz varicose all right my friends that covers our entire discussion on Al I hope it made sense I hope that you guys enjoyed it

and as always until next time [Music]