Acute Leukemia | Clinical Medicine

What's up, Ninja Nerds? In this video

today, we're going to be talking about

acute leukemias. This is a part of our

clinical medicine section. If you guys

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let's dig in to the pathofizz. All

right, so let's begin our discussion on

the pathophysiology. So when we talk

about acute leukemias, this is basically

two different types. One is acute myoid

leukemia, AML, and the other one is

acute lymphoplastic leukemia or alll.

Now when we talk about these, these are

really disorders of hematopolesis. So we

have to define what that is. So

hematopoesis is basically imagine here's

your bone marrow right you know the site

of uh white blood cell production red

blood cell production platelet

production all of that's the red bone

marrow so we can define hematopoesis as

the site of blood cell production and

that occurs where in the red bone marrow

so for example let's say that I have

here a bone in this bone right we'll

have some red bone marrow that red bone

marrow is the site of where we're going

to make all our different types of cells

that circulate throughout the blood the

white blood cells this can be the

granulite and the a granular sites. This

could be your red blood cells and this

could be your platelets. Question you

may have is how do I take this bone

marrow and make all these different

types of cells? Well, that goes back to

your physiology. So, you have to

remember inside of the red bone marrow,

there's a stem cell. This stem cell is

called the hemocytoblast. So, the

hemocyblast is basically like a pur

potent stem cell which can make all

different types of cells. That's what

makes it cool. I can make red cells,

white cells, platelets, all these

different types. What's really cool is

that this guy can differentiate. So

imagine he proliferates himself and then

he differentiates to become more

specialized. So he's no longer going to

be this kind of cell. He's going to

become these two different types of

cells. This one over here is called a

lympoid stem cell. Let's write that out.

And this one over here is going to be

the myoid stem

cell. We have these two cells that are

different from that purotent stem cell.

What's really important at this point is

this is where we kind of diverge. So at

this point, if there's an abnormality in

this process, it's going to lead to

maybe the alll. If there's an

abnormality in this process, it can lead

to AML. We just have to figure out where

exactly in this process. Let's come down

this arm first. My stem cells what can

happen is they can actually further

differentiate. And what happens is they

can differentiate into what's called a

myoblast. And myoblasts are important

because myoblasts will then further kind

of like change their neutrfil, become

more segmented and they can become

granulitic white blood cells. So again,

which one's this one called? Just so I

can be very very specific. Myoid stem

cell to a myo

blast. Now the thing here is whenever I

have a myoblast, this is going to make

my granulosytes. And there's different

types of granular sites here, right? So

we have

neutrfils, we have

eocinophils and here we have

basophils. These are all really

important because they are going to be

derived from that myoblast as a whole.

We call these a very specific type of

white blood cell. You know what we call

this one? We call these granulositic

white blood cells or

granulosytes. So here's what's

important. A myoblast can turn into all

of these different types of white blood

cells. The next component here is that

sometimes this myoid stem cell can also

differentiate into some other different

types of cell lines. I'm not going to

write them down, but it can become a

what? An ariththroblast. An

ariththroblast can then further

differentiate and become a red blood

cell. So this could become a what? A red

blood cell. Or it could further

differentiate from this myoid stem cell

and become a

meggaaroblast which then eventually

becomes meggaarasytes and blows up into

a million pieces and becomes platelets.

And then lastly this this actual myoid

stem cell could also differentiate

further and become a monolast and

monoblast actually could go further and

then turn into a monocight. So this

could become a

monocy. So this is your basic like

physiology when it comes to

hematopolesis. When we talk about this

with acute myoid leukemia, the problem

exists here that you have lots of

myoblasts. So really this is what's

happening. The bone marrow is producing

tons and tons and tons of myoblasts. So

that's really where this disease comes

into play. You have increasing amounts

of myoblast. If you really want to

define it, if I were to take the

percentage of these cells and how much

they occupy within the bone marrow, you

have to have at least greater than or

equal to 20% of these cells in the bone

marrow. So, I really need a lot of these

things. That's a significant proportion

to account for inside of the bone

marrow. Now, with myoblast, the question

is is why am I making a lot of these

myoblast? We'll get into that, but the

myo stem cell can differentiate to a

myoblast. But what if I shut down the

myoblast further differentiating? It no

longer turns into a neutrfll. It no

longer turns into an eosinaphil or a

basopil. And sometimes this could even

affect your monocytes as well. If that's

the case, this builds up and then all

this guy does is he just keeps

replicating onto himself. He keeps

replicating and proliferating and then

what do you get? You get a substantial

amount of myoblasts. When that happens,

guess what? You have you have acute myo

leukemia. Now, AML is interesting. With

AML, there is eight subtypes. And I

don't want to go through all of them

because it's not as high yield as when

we get into all. But we kind of say

these are M0 to M7. And the most

important subtype that you actually do

have to remember because it's pertinent

because it changes a the whole prognosis

of the patient. it's a different

treatment for the patient is APL and

this is the M3 subtype. So the

M3 subtype of AML is also referred to as

acute prominitic leukemia. This is the

only one that you have to remember as

the subtypes and the reason why is this

one has a completely different treatment

and prognosis. This can lead to DIC

that's worth knowing right? Absolutely.

Here's a question I think I had when I

was learning this topic. How in the heck

would I know if a myoblast is building

up inside of the bone marrow? Well, one

of the things is some of these

myoblasts, they seek seep into the

bloodstream. And if I got a blood smear,

I may be able to find these things. But

the best places to take it out of the

bone marrow. And when I look at these

myoblasts, they have special types of

markers on them. And so what we would

see is when you actually look at these

under the microscope, you would see

these things called our rods. You see

these like little these little pink

structures right here? These are called

your hour rods and these are an

identifier. So when you see these on a

bone marrow biopsy or if you get lucky

and you see on a peripheral blood smear

that's very specific for AML. Another

thing you see all these like maroon

dots all these maroon dots are a special

type of like enzyme that's present

really in myoblast and not in

lymphoblast. You know what that's

called? It's called myoparoxidase or MPO

we commonly abbreviate it. So if a

patient has the presence of our rods on

peripheral blood smear or their biopsy

if they have the presence of this enzyme

when we do what's called

flowcytometry that's really suggestive

of

AML. There's another thing I'll talk

about it just because we're going to

talk about it over here and I don't want

you to think that they don't exist. But

you see these like little blue proteins.

These little blue proteins are called

cluster differentiation proteins and

they differentiate different types of

white blood cells. There's a bunch of

them and I don't think they're super

worth a squeeze, but I just want you to

know that they do exist. And this is

CD13 and 33. If these do tend to be

positive, it's not going to be super

super specific for AML as compared to

the mo and rods, but it is worth knowing

these are identifiers of the myoblast.

So I got a bone bone biopsy. I see the

myoblast. I see this. I test for these

things. Oh, baby, that's a myoblast. And

then all the downstream consequences

that can occur in this become more easy

to understand. All right, we now move

into the acute lymph plastic leukemia.

Lymphoid stem cell. This one turned into

a myoid. And look, look at all the

things that could go from there. The

lymphoid stem cell is not as much. It

really just becomes a lymphoblast. So

here we're going to have a lymphoblast.

Then from the lymphoblast it then

further differentiates and when it

further differentiates it differentiates

into what's called T- cells and into B

cells. Now technically we call these

Tlymphosytes and we call these

belymphosytes but for right now I'm just

going to write T- cells and B

cells. Okay. So here's the pathway now.

So we saw from the myoid you can make

red cells, platelets and all these

different types of granulositic white

blood cells and monocytes. From lymphoid

stem cells, you really only make T-

cells and B cells. And if you want to go

a little extra mile, it makes natural

killer cells. Don't go too crazy. But

the problem in this disease is the same

thing. It's right here, the lymphoblast.

It's not

fully differentiating into T- cells and

B cells. And all it does is it just

keeps replicating on itself. And as it

replicates on itself, you build these

puppies up inside of the bone marrow. If

they build up in the bone marrow to the

point where there's so many

lymphoblasts, how many I put there?

Three. We'll do three here again. So

many

lymphoblasts. What's the percentage have

to

be? Greater than or equal to 20%. Baby,

that's a lot. So at that point, that's

now causing acute lymphoplastic

leukemia. The next thing I need you to

know is there's eight subtypes for AML.

What about the subtypes for ALLL? You

know, it's pretty cool. So, for this

one, it's only two specific ones that I

really want you guys to know

about. One is going to be T cell. All

right. So, watch this. I'm actually

going to bifurcate this puppy. So, we're

going to bifurcate this one. And when we

bifurcate this, we're going to say if I

have lots of these, let's say T-

lymphoblasts, lots of the T-ymphoblast,

I have too many of them, that can make

what's called T-C cell alll T-C cell

predominant acute lymphoplastic

leukemia. All right, way less common.

All right, way less common. Only

accounts for maybe maybe 20% maybe 20%

of ALLL. The more p-ominant one is when

these lymphoblast, the ones that are

made up here is if they're

belymphoblasts. This determines a

patient having B cell alll. And this one

is much more common

80%. So if I tell you what's the big

subtype to remember for AML, the most

important one is M3 or which one? It's

M3 or the APL. If I tell you which one

to remember for all, it's BLLL. Here's

the question. When I have to identify

the difference between a a T

lymphoblast and a B

lymphoblast, it's different. So, for

example, I'll talk about this later.

When we talked about APL, it really

differs. They still have ALS, they still

have MO, they still have these CD

proteins. What really diff between APL

and all the other of the eight subtypes

is that APL involves pro-yoccytes which

we'll talk about when we get down here.

For this one, they're both lymphoblasts.

So, their morphology is not really

different of their structure or the type

of cell and their stage that they are

during the differentiation. What really

helps to differentiate these is when we

look inside the cell. What are these

like little orange dots? These are

called TDT. So it's a terminal

deoxyucleotidile transferase. You you

don't need to know that whole thing.

Just know TDT. If they have the presence

of TDT on the inside of the cell, that

suggests all. All right? That's what's

really important to remember. This

suggests all. All right? Whereas if I

said MO, that one suggests AML. All

right? That's the big difference. Now,

cluster differentiation proteins were

not as high yield for the myoblast, but

they're super high yield for the

lymphoblast. So, look here. You see

these on the T? They're CD2 to CD8. So,

CD2, CD3, CD4, CD5, you get the point.

Anywhere from CD2 to CD8 suggests a T

lymphoblast.

But if I have cluster differentiation CD

10, CD 19, CD 20,

these are suggestive of Blymphablast.

That's what I need you to remember. So

the identifiers for

Tlymphoblast, let's actually make sure

this is very clean here. CD 2 to 8 that

suggests the

Tal CD

2 to 8. And if I say CD 101 1920, you

would say

Bympholast. All right. So we have our

identifiers TDT

alll CD2 to8 T alll CD 101920 BLLL. If I

said which one is the most important AML

subtype because it's promyo sites, you'd

say APL. All right, I think we got that.

Last thing I wanted to talk about is

that when you get to a blast technically

how when we talk about how lucapois is

making white blood cells occurs you

always start off with a blast then it

becomes a promyoite then it becomes a

miloite then it becomes a band cell and

then it eventually forms a functional

granular site I'm just using this as an

example right for lymphoid it would be a

lymphoblast a prolymphosy then a

lymphocy or b whenever we go through

these stages. If it's in the earlier

portions of the differentiation stage

here, that is

acute. These are the cells that are more

likely to be involved. The blast. So,

this is what's really important to be

remember this involves the blast.

Later in these parts where the nuclei

are starting to segment, they're

starting to become more specific and

more functional. That's chronic. So,

it's not going to be as many of the

blast now. You're going to have more of

the close to functional, but not quite

there. So, we're going to say a little

bit. We're going to say less

mature white blood cells because they're

not really blasts. You're going to have

a lot of these, but they're going to be

at the later stages where they're just

not close yet to being mature, but

they're definitely a little bit more

functional than these acute ones.

The problem with this is that blast

makes the progression of the disease

rapid. All right? So, this is rapid

progression. Whereas chronic is it's a

little bit slower because these are a

little bit more functional as compared

to these. They're a little bit smaller.

You're not going to have as much of that

devastating effect. And so, because of

this, this will be a gradual

progression. I'm killing it. Right. Mhm.

All right. So at this point we've c

talked about a lot the pathophys of

acute leukemias. What I need to now say

is okay what in the world is causing

these lymphoblasts to build up or they

don't differentiate but they just keep

proliferating. What causes the myo blast

to not differentiate but just continue

to proliferate. And then once we do that

we can say what's the problem? Why is

having so many of these myoblasts or

lymphoblast in the bone marrow out in

the blood or in the tissues a problem?

So with this we talk briefly and I mean

briefly about what we just said. When

you go through from a myoid stem cell to

a myoblast you go to what's called a

promyo site. Remember I told you that

most of the time if you have a myoblast

and you build these up that's your AML.

That's usually M0 to M7. So really

whenever this builds up significantly

that's going to be what's really

triggering a lot of this stage for you

know M0 to M7 except for so M0 to M7 AML

what's the only exception except M3. I

just don't want to write M012 and then

all the rest of them. So that's the big

thing there. But if I have lots of

these, if I have lots of

these. Oh man. Oh daddy. This makes the

M3

AML and that is defined as APL. So at

these stages what's happening is you can

have lots of blasts that can make these

types of problems for AML or you can

have lots of promyosytes that'll make a

lot of the problems for the M3 ML. AML

problem is they get stuck in these

stages and they never further

differentiate. The question is why why

does it get stuck in this proliferative

stage but not in the differentiation

stage and it's usually for acute myoid

it's genetic. So it comes down to

chromosomal

transllocations and so one of them

that's relatively important to remember

is for APL. That's why I kept stressing

that's the really important subtype to

remember out of the M0 to M7. For APL,

we care about a specific type of

chromosomeal transllocation and it's

called the

1517

transllocation. What happens is on

chromosome 15 you have a PML gene. On

chromosome 17 you have a raw alpha gene.

This is a retinoic acid receptor

receptor. What happens is you end up

swapping some of that genetic data and

you end up making a fusion gene. So now

I have a fusion gene which here's the

PML and here's the raw alpha. What do I

make? I make the

proyoite retinoic acid receptor alpha

gene. That's what it's called. So

PML R alpha gene.

When you got a lot of this gene, dude,

oh boy, it causes the promyoccytes to

rapidly divide but never differentiate.

That's the concept here. And so the big

thing to remember for why I talked about

acute milo leukemia, the specific

subtype APL or M3 is because this one is

defined as a 1517 transllocation. The

other ones don't really have that. Now

with that being said, in patients who

have what's called

tricomi 21 which is known as down

syndrome, these patients have a higher

risk of developing. So they're they have

a higher risk of AML. Do you know how

many times? 10 to 20 times. That's

significant. If a patient has Down

syndrome, they have a 10 to 20fold risk

of developing AML or ALLL. That's pretty

significant. So that's really important

to remember as a potential trigger

related causative factor. But basically

these genetic abnormalities are

basically shutting down the

differentiation but triggering

proliferation. Now other causes that I

think are just important to quickly just

check off is don't forget about chemo

radiation. So chemo radiation can have

that types of damaging effects and can

definitely lead to mutations that are

arising and that can cause proliferation

without differentiation. Other ones are

going to be milo proliferative

disorders. So

milo

proliferative disorders. We talked about

this in another video. So this was your

ones like polyythemeia vera, essential

thrombocythemeia, chronic milo leukemia

and primary milo fibrosis. All of these

carry that risk of converting into AML

because as they proliferate proliferate

proliferate you bring about the

opportunity for more mutations. And even

if you wanted to, I could add in another

one and but I'm not going to go too

crazy on this one. It's called

milo displastic syndrome. So this is a

disease where you have displastic white

blood cells and you can have blasts that

are starting to form but there's less

than 20% of them whenever it converts

from less than 20 to greater than 20 or

greater than or equal to 20. That's the

definition of AML. All right. So that's

the concept here. Now for all or acute

level blastic leukemia you have blast

goes to a

prolymphosy but it gets stuck right here

so it does not further differentiate and

so you don't go down this pathway and so

what ends up happening is you build up

these blasts right and this is what

leads to your alll which could be the b

type or the t type now when we talk

about these these are usually going to

be really important genetic causes so

one of them is a sign of a good

prognosis. And interestingly enough, we

see this in children. So often times

it's really really really I can't stress

enough really important to remember that

ALLL is a disease of little people. It's

a pediatric type of cancer. AML is a

disease of older individuals. CLLL, CML

are all diseases of older individuals.

But all is a pediatric disease. So

because of that, you're going to see

this in younger patients. So you're

going to see this as our pediatrics.

There's a very small

percentage, very small percentage of

people that can have all that could be a

bad prognosis, but we see this more in

adults. And this could also be due to a

genetic problem. What's the difference?

For the good prognosis, it's usually due

to a 12 21

transllocation. like the PML raw alpha

gene. I don't think it's as high yield,

but you have an EVT6 gene that gets

passed over to a RUNX1 gene. You're

probably like, I don't know what that

means. Don't worry about it. It's not

that important to remember, but you get

this

EVT6 and you get this RUNX1 gene and I'm

going to write them down, but please for

the love of everything, you know, and

holy, please do not memorize this. I'm

just trying to give you an idea that you

get this gene and this is the gene

that's responsible the same way the PML

raar alpha gene is there. This is the

other gene that's going to kind of put

the accelerator on proliferation but not

on differentiation. And that's what

happens. It just gets stuck here and it

just keeps proliferating. This is what

we would see in younger patients. This

is the one that I need you to remember.

This one not that common but you can see

this with a

922 transllocation. You take a BCR gene,

fuse it with an ABLE 1 gene. When you

fuse that, you get something really,

really bad. This is called the BCR Aable

one. So, this is going to be called the

BCR ABLE one gene. And what this does is

is this accelerates your tyrroscen

kinise pathway. And the tyrroscen kynise

pathway is going to do the same thing

that we've been talking about a million

times. It's going to put the accelerator

on proliferation but a block on

differentiation. That's what's happening

here. I already mentioned this before

but again tricom 21 is just a nice

little quick reminder that patients with

Down syndrome what happens they carry a

significant risk. Anytime you have this

you increase your

risk

of all and

AML by 10 to 20 times. That is the big

thing to remember. Okay. Other causes

again cheo radiation is a potential

trigger here. If you cause that

chemotherapy or that radiation it can

cause damage to cells and if you cause

that you can lead to mutations

obviously. And the last one is an

infection but it's a very specific one.

It's called the HTLV infection. This one

is only

specific only for T-C cell alll. Is it

really important to remember it?

probably not as much just because T-

cell ALLL only accounts for about what

20% but at least consider that. All

right, this is our causes. So at this

point we've said does a patient have

AML? It's the myoblast. I got a lot of

them in my bone marrow. There's eight

different subtypes. The most important

one is APL or is it AL? Lots of

lymphoblast, lots of them in the bone

marrow. Is it B or T? I now know how to

identify the differences between T and B

and how to know if it's a myoblast.

That's very very specific on bone marrow

and other special studies that we'll

talk about in the diagnostic section.

And then I even told you guys to

remember what are the most important

genetic causes that are happening where

we put the accelerator on proliferation

but the brakes on differentiation. For

AML the most important one is the 1517

transllocation. For all it's the 1221

rare cases 922. What's the disease where

you have three chromosomes which

increase your risk by 10 to 20%. That's

down syndrome. That's the big things to

take away from this. So now that we've

done that, I want to talk about the

havoc that these blasts myo or

lymphoblast have on our body when

they're in the bone marrow proliferating

or when they're in the tissues

depositing. Let's do that now. All

right. So let's talk about the classic

clinical findings that we see in acute

leukemias. When it comes to leukemia,

they have kind of a beautiful classic

picture I would say that you should be

thinking about. One of them is

pansyenia. The concept behind this is

that regardless if it's AML or

alllcellular bone marrow. For AML, their

bone marrow is filled with myoblast.

Whereas, if it's

alllast, when you have all of these kind

of building up in the bone marrow, they

take up a lot of space. They're pretty

honky cells, right? So, they're they're

they're chunky cells. And so with that

being said, you're going to crowd out

the bone marrow, per se. And by crowding

out that bone marrow, you make less

space in the bone marrow that's needed

for other cells to divide and to to

form, right? And so that's what usually

starts to happen is because of all of

this, you crowd out, we're just going to

use that in quotations, per se, you

crowd out the bone marrow. Now, when you

crowd out the bone marrow and you make

less space, what happens here is that

you don't have enough space for other

cells to develop, proliferate, and then

form, such as our red cells, our

platelets, and our white blood cells.

And so, because of that, we can't push

other cells out of the bone marrow into

the bloodstream. So, we're not forming

our red cells. We're not forming

playlist. We're not forming our

functional white blood cells. Now what's

it called whenever you have less red

blood cells? So whenever there is a

decrease in the number of red blood

cells and we measure this on our CBC via

what? Hemoglobin. So technically the

hemoglobin is what's actually going to

be low,

right? If we're really being

specific. When you look at a CBC, you'll

see that there's less red blood cells,

there's less hemoglobin, there's a lower

hematocrit. That might be the way that

you diagnose these patients as having a

form of the pansyenia the anemia

portion. How does anemia though? So this

is how we would define anemia, right? So

we would define this part as anemia.

Anemia could be a laboratory diagnosis

if the hemoglobin is less than 13 in a

male or less than 12 in a female. But

how would they come about

symptomatically? So anemia can present

symptomatically based upon the presence

of fatigue, palar, dysnia. These are

usually classic signs. But I'd say the

most common one is fatigue and palar.

All right. So that's one thing. You get

a CBC shows a lower red cell line. They

have symptomatic that could be anemia.

The next component here is what if the

platelets are lower? So if you have less

platelets now less platelets is pretty

straightforward. It's no specific kind

of like parameter like hemoglobin. It's

it's the platelets itself. So if they're

low, this is called

thrombbo cytoenia. And this is defined

as less than 150,000 platelets. When you

have less of these, the symptoms is that

of what platelets do. So red cells are

designed to deliver oxygen to the

tissues. So the reason why you develop

fatigue is because of less oxygen

delivery to the brain. You'll have

generalized weakness because of less

oxygen delivery to the muscles. You'll

have palar because of less oxygen

delivery which carries that reddish shoe

to the skin particularly to the

conjunctiva and as well as other tissue

spaces. With platelets they're supposed

to help you to clot and if you don't

have them you can't clot. So you will

bleed and so therefore the symptoms

could be bleeding and usually platelet

related bleeding or bruising is usually

kind of a classic picture. So the

bleeding is usually going to be things

like gingal bleeding, epistaxis,

minorio, prolonged bleeding from like a

cut. So those are things that suggest a

platelet disorder related bleeding. The

bruising is usually in very small little

blotss on the skin like pikia and

pipura. All

right, the next component here, this is

the interesting thing. When you think

about all these lymphoblasts or

myoblast, they're white blood cells.

They're just not mature. All right. So,

what could happen is, and this is what

usually can get people, you crowd out

the space, which leads to less space for

functional white blood cells. And the

most important one that we really care

about here is our neutrfils. And so, you

can get less functional white blood

cells. So, you can have a decrease, and

I'm going to be very specific. I'm going

to say functional white blood cells. And

this is defined as

lucopenia meaning you have a decreased

number of white blood cells. What's an

example again of the most important one.

So most the example here that I would

want you guys to think about is

neutropenia. All right neutropenia when

you have a decreased number of

neutrfils. Now here's the problem.

luccoytes. All right, they are white

blood cells. When you get a CBC and you

see, oh, the red blood cells are lower,

the hemoglobin, the maticus lower,

that's anemia. Oh, the plots are lower.

Okay that's

thromocytoenia. The white cell count may

not always be low. It's the amount of

functional white blood cells that'll be

low. Because what will happen is when

you get the white blood cell count,

you'll have the lymphoblast or the

myoblast plus some of these functional

white blood cells. Your white blood cell

count could be very high. It could be

normal. It could even be low. It really

depends. So, it's a variable white blood

cell count. What is important to know is

when you look at the differential. So,

the white blood cell count could be

pretty high, could be normal, could be

low. But when you look at the

differential, and that's the key, you're

going to have less of these neutrfils,

basopils, and eosinaphils, but neutrfils

is the most common. The reason why this

is important is functional white blood

cells are supposed to help you to kill

bacteria and viruses and infections. And

so now you can have

frequent

infections or fevers. This is where I

want to talk about an example of why

this is so

important. When you have all these

blasts that are taking up the space and

you have less functional white blood

cells that are circulating throughout

the bloodstream, especially neutrfils.

And how we truly define this is whenever

the absolute neutrfill count is less

than 500 plus a fever. This is a

oncologic emergency. So if a patient has

AML or all their neutrfll count when you

calculate their absolute neutrfill count

if it's less than 500 and they have a

fever this could be a sign of a really

scary disease and this could indicate

something called neutropenic fever and

it's actually worth remembering this. So

neutropenic

fever. This is the patient that if you

have a patient with an absolute neutrfil

count of less than 500 and a fever, you

don't know where that could be coming

from. And you have to assume that they

have a really bad infection going on.

Could be pneumonia, could be sepsis,

could be urinary tract infection. You

need to get blood cultures, urine

cultures, all different types of

cultures. Start them on antibiotics once

you get those cultures and try to sus

out what's going on. These patients are

super high risk and they can die. All

right. So with that being said, patient

comes in, they present with fatigue,

pallet, their CBC suggests that that's

the anemia component. They come in with

bruising, bleeding, their CBC suggests

thrombocyopenia that suggests a part of

this. They come in with variable white

blood cell counts, but when you look at

the differential, there's less neutrfils

and they've having fevers or they're

having frequent infections that accounts

for that component of pansyenia. You can

see this in either of these.

bone pain you're not going to see as

much in AML and it's going to be more

common in all. So for here's what I want

you to remember. I'm going to first off

starting by saying that this is less

common. This is more common. So less I'm

sorry more common for

all less common for

AML. Either way the same concept exists

that we talked about here before. or an

AML you're getting a

boatload of these myoblasts. In an alll

you're getting a boatload of

lymphoblasts and these things are

honking big man they're huge. So because

of that they're taking up a lot of

space. And not only does that space

factor account for less production of

other cell lines, it also starts

expanding the very undesirable uh tissue

who doesn't really want to expand. It

has to start to you know do that. So

then what happens is you start

experiencing a little bit of bone marrow

expansion. So what occurs here? you

experience some bone marrow expansion.

All right? And that's just because of

all these cells taking up all that space

in the bone marrow. This starts to

really occur. When you get a lot of this

bone marrow expansion, it occurs in

specific types of tissues, usually long

bones. What are the most common bones to

be affected here? Well, the pelvis is

going to be one. So, the whole structure

of the pelvis, the femur, and the tibia.

These are going to be some pretty common

ones. So think about any of the bones

that make up the pelvis. Think about the

femur and think about the tibia. These

are all weightbearing

bones. If you have bone marrow expansion

and it starts to involve these bones,

what will be the symptomatology? These

are designed to hold weight. Bro, what's

going to be the big symptom? The big

symptoms from this is a patient will

refuse to put weight to bear weight or

they'll start limping because of the

pain to kind of help with that process.

So it could lead to a limp or a refusal

to bear weight on that limb. So watch

out for a patient coming in with

pansyenia and symptomatology of that and

bone pain with symptomatology of that

should make you think of acute leukemia.

But if you want to really be specific

for the vignettes, it's going to be a

little bit more common having bone pain

with all, not as much with AML. That

comes to the last type of classic

presentation for

these. Whenever you have

AML, and it's a very specific subtype,

remember I told you that I told you

there's eight subtypes, M0 to M7. M3 is

the most important one. I'm only going

to quickly add this here that you can

have

M4 M5 AML which is called acute

monocidic leukemia. So this is where

that monoblast line is actually affected

believe it or not. In this one the

monoblasts actually come out here and

you get a lot of these puppies here.

They get pushed into the

circulation out of the bone marrow into

the circulation and from here these

cells go and deposit into the uh m mucus

membranes as well as the cutaneous

tissue. When they do that they cause

some interesting process to occur in the

gingiva. It can actually lead to a

process here called gingival hyperlasia.

And with that being said, not only can

that happen, but it can also cause these

raised bumps, raised like red purplish

bumps to appear on the skin. And this

can cause an uncomfortable sight as

well, which we refer to as

leukemia

cuts. So when whenever you have this

one, you should definitely think about

AML. It looks a little bit like

this. If a patient comes in and they

have mucaneous findings and panytoenia,

which one are you leaning more to? AML.

If I say a patient has pansyenia and the

bone pain, refusal to bear weight or

they're limping because of those bones

being affected, you would say more

likely all. How do we really iron out

other complications or presentations of

these two types of leukemia? Let's do

that. Now when we talk about these alll

acute lymphoplastic

leukemia in a perfect world you know you

may have a patient who comes in and they

present with pansytoenia and maybe just

some bone pain you make that diagnosis

but oftent times patients come in a lot

sicker and it's important to be able to

realize these presentations and to

consider them because they may come in

with some kind of like non-specific

stuff and it leads you to the diagnosis

of AL. What are those things? One of

them is

lympadenopathy. I like to think about

this easily. Um so lymphocytes love to

deposit into lymphatic tissue. So

whether that's nodal tissue like lymph

nodes or extra nodal tissue such as like

liver, spleen, other different areas of

the body. It's very common for

lymphocytes to deposit into these

tissues. So lympho blastic leukemia is

going to involve more organ involvement

whereas acute miler leukemia is going to

kind of really reside within the

bloodstream. That's where it's really

going to do its kind of problems. And I

think that's really important to

remember and it may help you to sus out

these two types of disorders and their

complication presentation. So

lymphodenopathy you get a lot of these

myoblasts right I'm sorry lymphoblast

you're pumping these things out of the

bone marrow into the bloodstream when

these lymphoblasts get into the

bloodstream they go and deposit into the

lymph node now you have these

lymphoblasts depositing here and they're

going to cause enlargement of the lymph

node that's called lympodinopathy how

would that present usually it's going to

be

painless

enlargement of lymph lymph

nodes. And what's the most common ones

to be affected? Well, it could be the

cervical lymph nodes, right? These are

definitely common. The axillary lymph

nodes are very common. The

superclavvicular, the inguinal lymph

nodes, and sometimes it can even get

into the mediainum. But I'd say the big

thing about this one is it's kind of

diffuse. It can hit a lot of different

lymphatic tissue. Cervical, axillary,

inguinal superclavicular mediainal.

That's one way that we can think about

this. Here's another thing. This chunk

of lymphocy, the lymphoplast, they get

deposited in here. They also pump out

cytoines. And so when they pump out

cytoines, they pump out things like

interlucan one and tumor necrotic factor

alpha which trigger the hypothalamus and

cause fever, chills, things that kind of

like are periodic and sometimes we can

call this B symptoms. So if a patient

comes in with fevers, chills, fatigue,

malaise and on top of that

lymphatinopathy painless

lympadinopathy, you think about

lymphoma, consider all. All right. All

right. The next one is a paddle

splinomegaly. Same concept here. Your

bone marrow is pumping out these

lymphoblasts into the bloodstream. And

these lymphoblasts when they're getting

pumped out into the bloodstream just

like there's getting pumped out here,

they can go and they can deposit into

the liver and they can deposit into the

spleen. When they do that and they

deposit into these kinds of organs,

they're going to cause the organs to get

larger and this is going to lead to

hpatosplenomegaly. HPA splenomegaly. One

of the biggest things to remember is

that your right side is going to be

occupied right upper quadrant liver,

left upper quadrant, spleen. It's going

to push everything in the middle. What's

right here in the epigastrium? The

stomach. So the stomach is commonly

compressed. So you get

stomach compression. What's the stomach

supposed to do? Don't you dare say, "Oh,

it breaks down my food, bro." It does.

Yes, but it's supposed to accept food

from the esophagus. If I compress the

stomach, I make it smaller. Whenever

food and fluids come into it, it

stretches and it's going to stretch a

lot quicker and it's going to reach that

point where you're going to be fuller.

It's kind of like acting like you have a

buriatric surgery essentially like you

did like a a lap band or you did a

vertical sleeve gasterectomy. It's the

same concept. I wish I had that

sometimes. But this scenario is going to

cause early satiety. You're going to

feel

full. Again, I wish I knew what that

felt like. Sometimes I eat like pizza or

the the the

the sink like a rat. But hey anyway

let's keep going. So we have a battle

splenomegali when these patients have

these big enlarged livers of big

enlarged spleens. Sometimes it can be

palpable but the biggest presentation is

early satiety or abdominal fullness. If

you actually happen to get images of

these it would look a little bit like

this. Okay. So we've seen now if a

patient comes in with lympadinopathy

they come in with a paddlomegaly

pansyenia bone pain you're thinking alll

let's add another thing now

lympadenopathy and pylonomegaly these

can all be seen in any type of alll cell

alll which one's more common so this

last thing you only see in T-C cell alll

so let's add that here this is only son

of a gun this is only in t- cell alll

only in T A L. And let's actually box

this so that you guys remember this is

the only thing that you'll only see in

this one and you won't see in B cell all

and it should make

sense. Bone marrow is pumping out what

lymphoblast. How do you identify it's a

T lymphoblast versus B lymphoblast? It's

got the TDT but it's got CD2 to CD8 for

T. CD1019 20 for B cell. Just a little

seeing if you guys remember from here

these tly lymphoblast they go and they

deposit into the thymus. This right here

this is this is your thymus. So now

you're going to get thyic enlargement

bro when that thing get

big. It has mass effect. So then it's

going to lead to a mass effect. All

right that mass effect is it means that

it's going to push on structures nearby.

Let's pretend where's my green marker?

Here it is. Let's pretend the thymus

gets bigger and it enlarges and

compresses this little brown tube.

What's that brown tube that I'm smashing

on? The esophagus. So, if I compress the

esophagus, all right, so if I hit the

esophagus, what would that look like?

That would cause

dysphasia, difficulty swallowing, right?

What if I compress this other guy? So

now it's good. A little green goo going

here, branching out into this guy.

What's this? The trachea. So now I'm

compressing the

trachea. What's that going to look

like? Well, it's going to decrease air

flow. That could lead to dysnia. And in

worst cases, it may even cause strider,

which is that really loud sound that you

hear during inspiration. So, they can be

short of breath or when they take a deep

breath in, it sounds like they're really

trying to squeeze air through a tiny

little hole because the diamond is

compressing on it. Here's the scary one

though. The scariest part of the mass

effect is if you compress the

SVC. So if you compress the

SVC. So now imagine

here that this guy goes over here and it

starts

compressing on the SVC. Are you going to

be able to get good venus return into

the right atrium? Now no blood's going

to back up from the superior vennea into

the brachiosyphalics into your internal

jugulars into your subclavians. What's

going to

happen? These patients can get real

sick. So they can have if it backs up

the J. So let's say it backs up. So

it'll cause backup into the internal

jugular vein. So the internal jugular

vein that's going to cause

face and neck swelling. If it backs up

via the subclavian veins, that's going

to cause

chest and

arm

swelling, right? because you're going to

be causing blood to back up and that's

going to cause the kind of enlargement

of the veins and on top of that it's

going to enlarge the soft tissue. So

they'll look like they have a big

swollen face, big swollen neck, swollen

chest and arms and it even gives a

bluish kind of like a light tinge of

bluish discoloration to it. This is

usually again what we would see here. So

it's going to cause compression. So,

you're going to compress this. So,

you're going to uh squeeze on the

internal jug of the vein, squeeze on the

subclavian vein, and you're going to get

all this

swelling. Now, here's what's really

important. This can actually become an

emergency if an SVC

syndrome you get so much backflow.

So if you get

backflow of internal jugular vein, this

can lead to impeded venus drainage from

the brain. You know the brain has the

sinuses which eventually drain into the

uh sigmoid and then the internal jugular

vein. Well, if you got a compression of

the super venne, it's already backing

up. That's going to cause poor venus

drainage because blood's supposed to go

from high to low pressure. But now you

have the outflow which is what's going

to come out of the brain into the

internal jug of the vein. It's high.

That's going to cause blood to back up.

intraranial pressure can go up. So this

could lead to an increased intraranial

pressure. Oh no, that's not good. The

second thing is it could back up the

internal jugular vein and what happens

is it kind of flows into these

collaterals near the larynx. Those get

enlarged and the larynx can get adeus.

If your larynx gets adeus, dude, you

can't get air flow into your airway.

That's terrifying. So sometimes it can

even cause luringial

edema in these scenarios. This is

emergency bro. This is you. This can

cause respiratory distress. This can

cause them to herniate. In those

scenarios, you got to get these patients

and get a stent in that vessel and open

it back up. Sometimes it's not common,

but if you compress the superior vennea

enough that you can't get blood into the

right atrium, you could even cause

hypotension. But you see it more because

it actually starts to really compress

the heart like a tamponot effect. But

that's not as I worry about these two

big ones here. All right. So, we see

this as being a pretty big concern here,

right, with T-C cell all. Well, is there

anything else? Yeah. So I had a patient

when I um I was I was in the

neuroscience ICU. young patient was

diagnosed with all and she ended up

having signs of menial leukemia because

what happens

is this disease sometimes man it can be

so rapid and so aggressive that they can

pump out these lymphoblasts and these

lymphoblasts they have sanctuary sites

the testes it's rare it's a rare finding

but it can go to the testes a higher

likelihood of a sanctuary site um is it

can go to the meningis and it can

deposit so here I'm going to show these

like little black dots here this is the

leukemic cells

depositing to the meningis they'll

create like a meningial reaction now. So

it's going to get like inflamed. So if

you have an inflamed meningis now that's

going to be called

menitis. They can get symptoms of

menitis. Dude it's just terrible. So

that what's that going to be? Well the

biggest symptoms is headache right

that's one thing because when you

involve the meningis you affect the

trigeminal nerve. You can also cause

nausea and vomiting. You can also the

meningi spread down into the neck. So

you can also get neck pain or nucal

rigidity. We'll put

EG nucal rigidity and you can even

involve the cranial nerves. So you know

cranial nerves three, four, six and even

the second nerve uh can actually be

affected and so you can even get cranial

neuropathies cranial

nerve pauses. The most common is going

to be cranial nerves two, three, four,

and six. So you can get dipopia and

blurred vision and papa edema. These are

characteristic findings of menitis. How

do I know if it's leukemic related? You

would need to do an LP. So I'd actually

have to do an LP test the cerebral

spinal fluid and look for that LP to

show me cytologology of the leukemic

cells. So another thing I would need

here is I would actually have to do an

LP. So I'd actually have to take and do

a lumbar puncture because again the

meninges you have that subacoid space

right you would be trying to tap into

that and take some of that cerebral

spinal fluid off and that would show me

what it would show leukemic cells. So it

show me lymphoblast and that presence of

lymphoblast with the

findings of this would be enough for me

to say okay this patient can have

meninja leukemia. We never want this. We

never want this. So you know what we do

whenever a patient has all this is what

happened to this young patient. She had

to get intratheal chemotherapy. So she

was diagnosed with ALLL but we have to

prevent the leukemic cells from

spreading to the meningis and so we'll

put in omia reservoirs or we'll do

lumbar punctures and squirt in the

chemotherapy to prevent those leukemic

cells from infiltrating that. That's why

it's really important to remember this.

All right. Okay. The last complication

now I want to preface tumor lis syndrome

can occur in both all and it can occur

in both AML but we see it more common.

So here I want to write this down. You

can see this. It's more common

in all, but you can see it in AML. The

concept behind this is that again your

bone marrow is pumping out the

lymphoblasts. When you have these

lymphoblasts, right? And and what we

find is that in patients who have all

they tend to have what's called

hyperlucytosis, like crazy crazy crazy

high levels of white cell counts. So

they can have very very high

luccoytosis. We call it

hyperlucytosis. All right. Problem with

that is that creates a tumor burden.

Imagine I have 450,000 white blood

cells. Could you imagine that's a high

tumor burden where if these cells for

some reason decided to die? In other

words, I trigger the initiation of

chemotherapy. What is chemotherapy

supposed to do?

It's supposed to kill these cells. So

that's what I want to do is I want to

stimulate these cells to

die. But when I do that, they pop open

and release all their super super

important contents like phosphate, like

potassium, like uric acid and we see the

presentation of tumor lysis syndrome.

That's why when a patient has all and we

start chemotherapy we need to monitor

for this and prevent this from

happening. So hypercalemia what we know

about this from cardio from renal is

that this has a very profound effect on

the cardiac system particularly the

electrical activity and so what we may

see is we may see

arhythmias

or we can see the classic ECG changes

and this is what they like to to test on

uh for the exam. What's your uh ECG

changes that I need you guys to

remember? Let's let's highlight them.

What's the first presentation you always

remember? Go up this way, down, and

back. So up is your peak T-wave. Second,

as you go back, the prolong PR interval

down you flatten the Pwave. Back to the

right, you widen your QRS complex. From

here, if this progresses, it can become

a sine wave and break down into VIB or

ASY. Can you imagine how dangerous that

is? So when we have a patient who gets

chemotherapy, they have all we like to

put them on telemetry where we

constantly monitor them for any ECG

changes or arhythmias. What kind of

arhythmias can they develop? I just told

you they can have brada

cardia. So they get brada cardia or they

could have cardiac arrest. So they can

go into cardiac arrest. This could be

asy or vib or they could also develop

brada cardia particularly a blocks. So

they can develop like a first degree,

second degree, third degree AV block. So

this is important thing to remember. So

we got to watch out for this. Now

hyperasemia is where it kind of gets

scary. So whenever you got lots of uric

acid, right? This uh let's represent it

with this like this blue dot here. These

little blue this is this is your uric

acid. When these little guys get over

here and they move across the

glomemeilus, what we see is that these

little sons of

guns are super toxic. They're

nephrotoxic. They get into these cells

here and they can

induce a nasty

toxicity and they cause damage to the

proximal tubular cells. So now I'm going

to have what is this called? Acute

tubular necrosis. So I'm going to have

acute tubular necrosis. That's I just

stimulated that by these toxic uric acid

crystals. Now what happens is when these

cells die, what do they what do they do?

Do you guys remember? They start sloing

off. So, let's imagine here I start

breaking up this

cell. And what I'm going to do

is I'm going to

start shedding off sloing off some of

that tissue. As I sloth off the tissue,

such an interesting word, sloth. As I

sloth off that tissue, what do I do? I

obstruct the flow of urine. Can you

filter things across if all the pressure

is built up in that tubes and in the

capsule? No, you can't filter this. Look

at this. All this is going to be

inhibited. Your GFR is going to go down

faster than you can ever imagine. And

because of that, what's going to happen

is this is called an obstructive

uropathy. So what is this called? This

is going to cause obstructive

uropathy. So

obstructive uropathy due to those nasty

cells and that's going to again cause a

drop off in the GFR.

an abrupt

one. All right? Because you're going to

build up the pressure. You're going to

build up the pressure in the capsule and

that's going to impede the net

filtration pressure. Now, GFR determines

the way that we clear metabolic waste.

My GFR is going down. Am I going to

clear metabolic waste? So, if I'm

impeding this process where things are

supposed to be filtered or secreted, now

this process is impeded. So, I can't

filter and I can't see creep because

these cells are damaged. Bro, that's

terrifying because now my creatinine can

go up and that's really what determines

the incidence of an AKI. That's really

whenever it goes up acutely, that's

determines what an AKI is. I can

also see the potassium, the water, the

protons, and the ura go up. So, what if

my potassium goes up? That's hyperlemia,

bro. Wait a second, Zach. They're

already at risk for hypermia. Exactly.

That's why this is such a disaster

whenever you have these two together.

The other thing is that the water can go

up. So, they can develop hypervalmia.

They can get volume

overloaded and then they can also build

up their protons. They can get

acidotic. And then lastly, if the ura

builds up, it can cause

uremia. And these are the concerns,

right? So I'm not going to write those

out, but again, hyperalemia,

hypervalmia, acidosis, uremia. It's

really important to remember that that's

the presentation of an acute kidney

injury. So an ATN is the way that these

patients will present with what we would

define as an AKI, an acute kidney

injury. This is why this part is super

critical to identify. The last thing is

so if a patient comes in, they got

kidney injury, they got hypercalemia,

and they got um a history of all, some

chemotherapy, and then another thing you

check their fossil levels. Fossil levels

are through the roof. You know what the

problem with phosphorus is? You don't

really think about it doing very much.

One thing it does do is it binds free

calcium. So, it loves to bind that free

calcium. If you got a lot of this sun to

gun and it binds up the free calcium,

what's going to happen to your calcium

levels? It's going to go down. Might

have less ionized calcium, bro. Ionized

calcium is important because high

calcium blocks sodium channels. Low

calcium doesn't block the sodium

channels. These things are going to fire

like a son of a gun. These neurons are

going to go absolute ham bone and

they're going to fire and fire and fire.

What's that going to present as?

Neuromuscular irritability. What's that

called? Tetany. I could come in with

shave tech sign, triso sign, what else?

Peroral paristhesas, seizures. It's

pretty

terrifying. The whole point of really

identifying tumor licis syndrome is that

whenever a patient has this and they're

getting treated, you monitor these

things. And there's a pneummonic. I

don't know if it's great, you may hate

it, you may love it. I think it at least

gives me a basic idea of the

contributing factors. I like to remember

puke all in caps and then calcium and

lowercase

that phosphorus is elevated,

uric acid is elevated, potassium is

elevated. So this these two elevated,

calcium is lower case, it's decreased.

May help you a little bit to at least

remember that these are the the four

characters that are the problematic

issue in tumorlyis syndrome. Okay. Now

that we've done that, let's see what's

the big presentation for AML. All right,

so now we move on to the complications

of acute myo leukemia. Now it's really

important to remember that for acute myo

leukemia, can you get tumor lis

syndrome? Absolutely, you definitely

can. All right, so in acute myo

leukemia, they can get tumor lis

syndrome. All I wanted to emphasize is

that you see it more commonly for all.

The reason why I'm doing that is so that

they present it in the boards. They're

going to utilize that concept that it is

more common in ALLL. All right. So,

don't forget that. With that being said,

we're going to talk about luccoasis and

DIC because that's the two big

complications that you see in acute mild

leukemia. Can you see luccoasis in all?

You can. You definitely can. It's just

it's more common in AML. Let's talk

about these. So, luccoasis, what is

this? This is basically um a concept

here where you see it in AML, they pump

out lots of these myoblasts, right? So

you're going to get lots of these

myoblasts. Now remember I told you that

these account for white blood cells. So

when you get a CBC and you get a white

count that's like you know 300,000 these

are accounting for that. So the more

myoblasts you have the higher that white

cell count is going to be. The higher

the white cell count the more incidence

of luccoasis you're going to have. At

what

point in the bloodstream when you do a

CBC when these guys get into the

bloodstream at what point are you

concerned about luccoasis? We get

concerned about

luccoasis whenever the white blood cell

count is greater than

100,000. At that point we start saying

that okay there's so many myoblasts here

in the bloodstream that what it could

actually do is is it could do a couple

things. One is it could decrease the uh

it could increase the viscosity of the

blood. So you're going to increase blood

viscosity and then that's going to start

causing little occlusions. these like

little white cells, they can start kind

of like shoot and they get stuck in all

of these like microvasculare. And so

then what's going to happen is you're

going to get

microvascular occlusions. So now look at

this. If I get these white cells and I

have so many of them that they flow

through here and they start kind of

accumulating here and they get stuck in

these like smaller micro vessels. Blood

which carries oxygen is supposed to be

moving through this to these tissues. Am

I going to be delivering oxygen to these

tissues now? No. As a result, there's

going to lead to decreased O2

delivery. That decrease in O2 delivery

because of these white cells plugging up

the microvasculare can then present

with organia. And the reason why is if I

start stimulating organia, this can

present in different organ systems.

For example, let's pretend these tiny

little white cells get stuck here in the

microvasculare of the MCA or in the

microvasculare of the ACA or in the

microvasculare of the PCA or the

microvasculare of the vertebrate. You

get the point. They're clogging up these

areas, decreasing oxygen delivery. It

could be to the point where it causes

mild symptoms, sometimes headache,

dizziness, right? But the scariest fact

is if it causes enough blood flow to be

reduced to the brain where they start

having neurological deficits, but they

can it's only transit. They go back to

their normal status. What's that called?

A TIA. So in mild cases, it could be

just a headache and uh dizziness. That

could be the most mild scenario, but it

could get worse, right? It could then

progress to a TIA where you have

transient eskeemic attack or it could go

all the way to the point where you

develop a true infarct of the brain.

Here's an infar. Right? That's the scary

concept here. So I could actually

infarct this tissue if I'm not giving

enough oxygen supply. It could start off

where it's just headaches. Right? That

could be the first symptom. Then it

could then progress to a TIA. Worst case

scenario, it can progress to a CVA. So

this is usually in the order of how it

may

progress. Sometimes they may go straight

to a stroke. It might just be too bad.

So that's one thing. The second thing

that I need you guys to think about is

it could also kind of plug up the flow

out of the retinal veins. So imagine I

olude the retinal veins. Well, retinal

veins are supposed to bring blood out of

the retina here. But now that's going to

be impeded because I got this occlusions

here. If I olude that all this blood

proximal is going to start building up.

These retinal veins are going to get big

as a son of a gun. Look at these. Look

at these things. Look at this.

These things are getting huge. That's

going to cause dilated retinal

veins. If you get dilated retinal veins,

the problem with that is that you cause

a back pressure in the retina. And that

back pressure, the issue with that is

that it can cause hemorrhages to form

within the retina. So sometimes this may

cause what? It may cause retinal

hemorrhages. Now another thing that's

really important to remember is that you

have the optic disc. That's where like

your retinal artery, the retinal vein

kind of through that area and even have

the optic nerve. Sometimes when these

retinal veins get super engorged and

dilated, they cause the enlargement of

that optic disc. That's called

papadeema. Papaladeema.

When you have this, when you have

papadema, that's one thing that may

cause the blurred vision. Retinal

hemorrhages could cause blurred vision.

These are the big things to remember. So

often times with this type of

presentation, one of the big ways that

these patients may present is they may

present with that blurred vision. So

this could be the fundoscopic findings,

but this could be the symptomatology of

those fondoscopic findings. So watch out

for that. Could they be presenting here

with blurred vision? That's the big

thing to

remember. The other one here is that

sometimes these little white cells can

plug up the pulmonary arteries. Could be

in like the more distal ones, but it

could plug up these pulmonary arteries.

What are these supposed to do? Well,

blood's supposed to go from the right

atrium to the right ventricle to the

pulmonary arteries to the pulmonary

capillaries where we deliver oxygen. I

mean, where we actually pick up oxygen

at the alvoli, drop off CO2. Now,

because of that, you're going to get a

decrease in the gas exchange at the

alvoli. So, you're going to get a

decrease in the

alvolar gas exchange. If you don't

exchange those gases, you're not going

to be able to have a good oxygen. So,

you're going to end up with what's

called hypoxia that may be evident on

the patient's SPO2. Or they may come in

with dysnia because of the hypoxia. They

may come in with an increased

respiratory rate to compensate for their

hypoxia. They may be working hard to

breathe to compensate for their

hypoxia. These are the things that you

want to be looking for. So because they

can get microvascular occlusions in

their pulmonary circulation, they can

present with hypoxic respiratory failure

or dissant due to their hypoxia. They

can present with neurological deficits

in worst case scenarios and they can

present with blurred vision due to the

fundoscopic findings. All

right, man. That's luccoasis, right? And

again, luccoasis is a pretty severe one.

Now, here's what's interesting. So you

you're probably asking, okay, Zach, I

feel like you said back there that all

can have hyperlucytosis. So wouldn't all

lead to luccoasis more likely than AML

since their white counts tend to be

higher? You would think that. But what

we found is that there may be other

alternative reasons, and this is what's

interesting, as to why AML develops

luccoasis more than all. It may not just

be the elevated white count alone. It

may be something else present that we

just don't know yet. But for now, white

counts greater than a thousand with

symptomatology is luccoasis. Which one

do you see it more commonly in? It's

going to be more

common in AML, but you can see it in

all. All right, cool. Next one. DIC.

This one you're only going to see in

AML, but again, it's specific. It's only

in a subtype. Remember, mediaal masses

are only found in uh TALL. Well, in DIC,

you're only going to see that in APL,

which is the M3 variant of AML. So, it's

only going to be in APL. Now, if you

remember with APL, the bone marrow is

going to be pumping out a lot of these.

It's not the blast. What was the big

difference? You had that fusion gene,

the PML

procinoic acid receptor alpha gene that

was in the

processes. So, these are going to be

your proylotes.

They're like one stage after the blast.

So, you're going to have a ton of these

little sons of guns. Now, promyocytes

are dangerous. And the reason why is

they secrete lots of chemicals that

these blasts don't usually secrete. And

so, when they get into the bloodstream,

when they infiltrate into the

bloodstream, these are disastrous, dude.

So, for example, they can release things

like tissue factors. So remember tissue

factor that's something that activates

the extrinsic pathway because it binds

with factor 7. It can also release all

these different types of

coagulation factor activators. So it can

activate other coagulation proteins. So

the whole point here is that you're

releasing certain things that are going

to do what? Trigger the coagulation

cascade. So I'm going to increase the

clotting proteins or I'm going to

increase my clotting

cascade with this concept here. So these

little promyioytes are sons of guns.

They release tissue factor. They release

these activators of the coagulation

cascade and that pumps up my clotting

cascade activity. Now if I have clotting

proteins, what do I need in order to

bind to the actual vessel first to start

a clot? I need platelets. So I need

platelets present to be able to help

that process. So what happens is the

platelets will start sticking to the

endothelium. When the platelets stick to

the endothelium that activates other

coagulation factors and these

coagulation factors will then start

again triggering that fibbrin mesh to

form. So pl start the primary hemostatic

plug and the coagulation cascade leads

to the secondary heistic plug. Either

way, the combination of these two are

what I

get to form these micro throi. So now

what ends up happening is in DIC I get

widespread micro

throi. These widespread micro throi can

lead to organ eskemia. But here's the

problem. Here's where it really gets

bad. When you use these clotting

proteins, and I'm talking you you make a

lot of these things, dude. You make

clots all over the place.

You consume your clotting proteins, you

consume your platelets. So what ends up

happening here is you end up with two

effects because of the

consumption of platelets and the

consumption of clotting proteins to make

all these

throi. What ends up

happening? So I increase the consumption

of pllets. I increase the consumption of

my clotting proteins. What does this

do? The problem with this is I have

these micro throi, but now if I have a

little nick in my uh vessel here, I

won't have the platelets or the clotting

proteins to stop the bleeding. So now,

as a result, these patients can have

clots and they bleed. That seems

paradoxical, Zach, but that's what

happens here. So, they can get bleeding.

This could be in the form of what?

Echimosis, GI bleeds, brain bleeds. This

could be uh prolonged bleeding after

surgical procedures, oozing from IV

sites. The list goes on and on and on.

But this is usually bleeding that's

going to be presenting because of the

consumption of platelets and the

consumption of clotting proteins. So, if

I have a new nick, I can't stop that.

All right, that's interesting. So, a

patient can have thrombi and they can

bleed. That is kind of interesting. But

here's what gets worse. The

promyosytes, not only do they release

these things to cause the clotting

cascade, which eventually gets consumed

that causes bleeding. But they also

release something called, so here's my

promyite. They release something called

a nexin

2. Now, don't go too crazy. All I want

you to know is that it's basically

increases the activity. It leads to

increased activity of plasmine

eventually. Now

plasmine if you guys remember helps to

break down fibbrin and fibbrinogen. And

so what it's going to do is it's

actually going to break down some of the

clots. And so it's going to lead to the

breakdown of fibbrin and

fibbrronogen. This starts breaking up

clots. Dude, what's that going to do?

That's going to further worsen the

bleeding. Oh my gosh. So, not only do I

have thrombi that are forming because of

the consumption of the plates and the

clotting proteins, but I end up

consuming them, I have less of them to

stop myself from bleeding. And then on

top of that, these dang

proyoytes, they release things that

break down clots. So what do I end up

doing any even more? Again, I trigger

more bleeding. That's why this is

disease is super super super scary and

it's something that you have to be able

to

recognize.

Now the next concept here, okay, we have

patients that bleed and they have clots.

But here's another thing. When you make

these micro throi, right? You know who

um just unfortunately get the brunt of

this sometimes? Here's all these micro

throi. Red cells are just a little bit

too big. So when they run through these

micro throi, they get shredded to

pieces. It's terrible. And when they get

shredded to pieces, they make these like

weird shredded up cells. And what are

these called? These are called

shisttoytes. So these patients will have

shistytes. The only way that you can

truly see shistytes is you look on a

peripheral blood smear if the patient

has anemia. So they can get anemia and

they can have the presence of shistytes.

So one of the ways that we truly

diagnose a patient having DIC is they'll

first start with

bleeding, skin bleeding, echimosis or

petiki or they can have prolonged

bleeding from surgical sites, they have

GI bleeds, they have uh brain bleeds,

they have oozing from IV sites, all

these different things. Either way,

they're bleeding. And on top of that, we

get certain types of labs. First thing I

do is I get a CBC and I show that my

platelets are low. So, what would I see

on my labs? My labs are the key thing

here that helps me to make the

diagnosis. So, yes, it's not just the

bleeding, but there's certain

labs. One thing is I'm going to because

of the consumption, I'm going to have

less platelets, right? So, my platelets

will be

low. I'm going to rip up my red cells.

So my red cells are going to be low. So

I'll have a lower

hemoglobin. All right. If I look at the

peripheral blood smear, I'll have

shistytes on the peripheral blood smear.

If I look at because I consume my

clotting proteins, I can't now stop

myself from bleeding. What happens to my

coagulation labs, my PT, my PTT? Those

all go up. So I have an increased PT and

PTT because I'm making clots all over

the place. What's one of the things that

tells me if I have a heavy clot burden?

D- dimer. So D-dimer will be elevated.

And because I have consumed so much of

my fibbrin and fibbrinogen because I'm

breaking down the clots, what happens to

my fibbrronogen level? That goes down.

Do you see why I break this down? that

precipitates bleeding but it also lowers

your fibbrronogen. So then you have a

low fibbrronogen. These are pretty much

characteristic for DIC. Okay my friends

at this point we've talked about acute

leukemas with respect to the patho the

causes the classic findings the

complications. Let us move on to the

diagnostic approach. Putting all of this

together is really the key right because

we've talked about a lot. So if I see a

patient who comes in with potentially

fatigue and palar I want to think about

anemia. If I see easy bruising and

bleeding, I want to think about

thrombocyopenia. And I hear that, oh,

they've had a couple infections this

year and they've had frequent fevers, I

want to think about neutropenia. These

things are telling me the sign of

pansyenia. And I can get a little bit

more specific. And if they say anything

about bone pain or having difficulty

bearing weight or limping, I think alll.

And if I hear mucinous lesions on their

manifestations of their physical exam,

I'm thinking AML. So, okay, I want to

prove the panytoenia and I want to look

to look at the specific type of cell in

the blood in the bone. So I get a CBC.

I'll get make sure it's with a

differential so I can tell the types of

white blood cells and then I get a

peripheral blood smear to get an idea of

what's that the actual cell in the blood

and see if it can help me determine if

it's lymphoblast or myoblast. So if I do

the CBC with diff and I see that they

got pansyenia all those cell lines are

are low that would support these

symptoms. And if I see they have lots of

blasts on their differential oh okay

cool that tells me that these are

definitely more of the acute types of

features. This could be an acute

leukemia. I have to look at the actual

blood smear and say, is it lymphoblast

or myoblast? So, if I look and I see

lymphoblast, that's very helpful. When

you kind of look at a blood smear here,

you can kind of see I have a lot of red

blood cells here. When I zoom in, look

at all these. These are tons and tons

and tons of lymphoblast. And when you

really zoom in here, you can kind of

notice, oh yeah, wow, these are very

large appearing cells with a very large

nucleus and large cytoplasm. This is

characteristic of my lymphoblast.

Now it doesn't guarantee that the

patient has um alll. The reason why is

this is just in the peripheral blood. I

actually have to confirm that this is in

the bone marrow. So I would have to

follow up and get a bone marrow biopsy.

But let's say that I move to the next

step which is all right. I have another

patient who has a differential that

shows pansyenia. They got increased

blast. Maybe they have mucaneous

lesions. And when I look at their blood

smear I see myoblast with our rods. And

so when I zoom in on this portion here I

see oh wow this is definitely a really

huge nucleus. Oh, what's that? That's

our rods. Our rods. Oh, that was always

associated with acute milo leukemia.

Again, not a guarantee, but it's very,

very likely. The only way that I can

prove all of this is I got to get a bone

marrow biopsy and send that sample off,

look for those CD proteins, look for the

TDT, look for the mo and really figure

out, is this a lymphoblast or is it a

myoblast that's in the bone marrow

causing all of these problems. So if I

see greater than equal to 20%

lymphoblast on the biopsy, boom, it's

all I got it. If I got greater than

equal to 20% myoblast on the biopsy,

boom, it's AML. But then the question is

with with all is it T or B. That's where

the flowcytometry and

imuninohystochemistry comes in. If I do

that and I see CD10, 19, 20, and TDT, ah

dude, that's the Bly lymphoblasts. And

if I see, oh, it's CDT but CD2 to 8. Oh,

that's the Tlymphoblast, right? And then

you know what we can actually say is I

can get cytogenetic studies which really

look at the types of mutations or

chromosomeal transllocations. And

remember there was two 1221 922. If I

got 1221 that's for pediatrics it is

good prognosis. And if I get the 922 the

Philadelphia chromosome that's in adults

that's bad prognosis. That's also

something that we can do from this study

because it helps to guide kind of our

treatment progression. Now with AML

there was like eight subtypes. Again,

you can actually look at these on the

biopsy and kind of get an idea. If you

really wanted to know specifically

though from those um which type, again,

you could do the CD13 and 33, but the MO

is the really big one. If you see

myoparoxidase that's actually present on

their uh flowcytometry or their heisty

chemistry from a myoblast from their

bone marrow biopsy, it's AML. What you

could then do is take it a step further

and get the cytogenetics. Why? Because I

want to look for one specific

chromosomeal transllocation. Remember

1517. If I find the 1517, what was that

associated with? Come on, spit it out.

APL. All right, that was the PML raar

alpha gene. All right, fusion gene. All

right. Now, what if I have a patient

coming in with complications like some

scary ones that we talked about? We

talked about a lot of them. Let's put it

together. So, if they come in with these

oncologic emergencies, per se. So, I see

stroke symptoms. So they have he maybe

there's some dizziness some TIA they

have some focal deficits they have

shortness of breath they have hypoxia

and I get a white cell count and it's

greater than 100 thousand they have

hyperlucytosis and organic eskeeia

symptoms that's luccoasis if I hear

menitis symptoms headache nausea

vomiting nuclear rigidity some cranial

nerve pauses what am I thinking I'm

thinking menitis but I'd have to prove

that by getting an LP to see the

leukemic cells if I have face neck arm

swelling and in worst case scenario

their intraanial pressure is high so

they're neurological deficits or they're

having respiratory stress from lingial

edema. I'm thinking SVC syndrome, right?

Especially the T- cell ALLL. And if I

hear coagulopathic bleeding, so I hear

that they're having a lot of hem

hemosis, echimosis, bleeding from IV

sites or from catheters, they're having

uh a lot of these problems, I'm thinking

DIC, especially with APL. And if I hear

that their creatinine bumped up

significantly, they're having um

arrhythmias that are showing PT waves

and prolonged PR intervals and dropping

of their P waves and widening QRS

complexes. I'm thinking about the hyperc

calmia factor. And if I hear that gout

flare and the AKI, I'm thinking about

that uric acid that's causing a lot of

these diseases, especially we see this

in all. This one AML, ALL, T-C cell, and

APL. Now we can really thoroughly

evaluate all this and this is kind of an

initial stuff. You can get coagulation

studies and you can extend that out. We

can get a PT, PTT, we can get an INR. We

can look at fibbrronogen. We can look at

a D-dimer. All this is trying to do is

prove this uric acid. I'm trying to

prove if there is potentially um

especially with combination with a CMP.

If their uric acid's high, their

potassium is high, their phosphorus is

high, calcium is low. I'm looking for

tumor lysis syndrome. CT chest with IV

contrast. I'm trying to see if the SVC

is compressed. I'm looking for SVC

syndrome. And a loop a lumbar puncture

is looking to see if there's leukemic

cells that support menial leukemia. So

again, a lot of this is really putting

it together. So it technically lucosis

is a clinical diagnosis. You need a

white cell count, a greater than 100,000

hyperlucytosis, and es schemic symptoms.

That's the diagnosis. Then if I hear

that a patient is having some menitis

symptoms, I get a lumbar puncture comes

back negative for really any kind of

disease like bacteria or viruses or

fungal. But when I throw off

cytologology from tapping in there and

it comes back positive for leukemic

cells, it's meninja leukemia. If I get

that CT with IV contrast coming through

here, the chest and I say, "Oh my gosh,

there's a big goober here and it seems

to be, oh, that's the SVC. Look at it.

It's tiny as can possibly be. That's

probably my superior venneava syndrome."

And if I have a patient who's bleeding

and then I look and I get their PT and

their PTT and it's elevated, they got a

low fibbrinogen, a high dimemer, and add

on that other thing, they have

thrombocyopenia, they got shista sites

on their blood smear, that's really

supporting that DIC picture. All

right. And then lastly, if I hear a

patient has, you know, arrhythmias,

they're having high potassium on their

CMP, high uric acid when I test that,

their phosphorus is high, their calcium

is low, and they maybe got a recent dose

of chemotherapy, I'm thinking about

tumorlyis syndrome. All right? So, this

is really a very comprehensive approach

in that sense. But before we treat the

disease, we should treat some of these

acute complications. And we talk about

this in a lot of different systems, but

it's always good to have overlap because

you'll remember it when it's actually

necessary. So in tumorlyis syndrome, the

problem here is that you get a lot of

these crystals, the uric acid crystals,

and they can really cause a lot of

damage. And sometimes there's not a lot

of evidence, but you can try and really

fill their vascular system to flush some

of these uric acid out um and pres

prevent the actual precipitation of

them, which can worsen kidney injury. So

it's always good to maintain good IV

fluid resuscitation just to avoid volume

overload. The problem with tumor lis

syndrome is the uric acid. You want to

try to lower that as much as possible

because if you go back to your kind of

biochemistry whenever these cells pop

open they release purine nucleotides

that can convert into hypoanthine and

xanthine and then to uric acid. Uric

acid is the problem. This is the one

that kills the kidneys and causes that

nephrotoxicity. Right? So we have

enzymes that help in these process.

Oxidase helps to make this step and it

also helps in this step. Well, if I had

a drug theoretically that could inhibit

zanthinoxidase like alopurinol, what I

may be able to do is reduce the uric

acid because it's going to inhibit these

steps and so I'll end up with like less

uric acid potentially, right? And that's

less nephrotoxicity. Problem is is that

it's only going to inhibit what kind of

like in a in a degree it's inhibiting

uric acid formation in a patient who has

tumorlyis syndrome and they already have

uric acid out there. It just prevents

further uric acid, but it doesn't

actually reduce that already present

uric acid. And so that's why it's really

only good at decreasing uric acid before

it's formed. That's why it's more of a

prophylactic therapy. Whereas

rasburease, this is actually better in a

acute scenario because what rasbase does

is let's say that uric acid's really

high and I give them a drug that

actually can convert uric acid into a

very less toxic form that can be easily

excreted from the kidneys. there's no

nephrotoxic effect. That would be great

because I convert a lot of that deadly

stuff into the less toxic stuff. That's

where raspberase comes into play. It

actually helps to convert uric acid into

alenon which can be excreted very nicely

and it doesn't cause any defrotoxicity.

That's the benefit of raspberase. So we

use this in an acute event and this is

more of a prophylactic event. But IV

fluids should be given no matter what if

we're concerned about this. All right.

Now with luccoasis the problem is we got

tons and tons of white blood cells. We

got to lower them. So acutely what

you'll probably be doing is two

therapies up front. That's at least what

up to date supports which is hitting

them with hydroxyurora. It's a cyto

reduction agent. So it hits the bone

marrow and shuts down the production of

mostly a bunch of different cell lines,

red cells, platelets, and white cells.

Problem is is it kind of takes a little

bit of time. So it's good as more of a a

chronic and preventative or prophylactic

effect. Uh but when you need to rapidly

remove white cells, this is really the

thing that you want to do is add on

lucaperesis. So lucaperesis basically

you're going to remove the blood from

the patient right which has all of these

heavy amounts of the blast in this case

since we're talking about luccoasis

we're talking about AML all right so we

want to remove a lot of those and then

what we want to do is we want to

centrauge it to separate it onto layers

and then we're going to get our red cell

layer our buffy coat layer which

contains the platelets and the white

cells and then you're going to get your

plasma all I want to do is get rid of

those white cells all of those excess

myoblasts and as I do that I can give

back the blood to the patient that I

have, you know, I don't have any need to

to actually remove like their plasma and

their red cells and their platelets. So

that's the goal of lucaperesis is to

rapidly reduce it. So we do that a lot

when they're severely symptomatic. All

right. Now DIC a lot of it's really just

supportive. If a patient has a low

platelets and they're bleeding, you give

them a platelet transfusion. If they

have a low hemoglobin, you can and they

have again potentially in this scenario

we wait for at least less than seven,

we'll transfuse them with the pack red

cell. If they have a bleeding and they

have an increased PT and PTT, you can

give them FFP. The thing about DIC with

acute leukemas, especially APL, is we

actually do have a specific treatment

and it's called all trans retinoic acid,

often times abbreviated ATRA. And the

cool thing about this drug is if you

guys remember the 1517 transllocation

makes the fusion ankop protein or the

fusion enco gene, which makes the fusion

encoin. And this put the differentiation

block on those promyocytes and said you

can't convert into a neutrfil or an

eosinaphil or a basophil. And so that

was the problem. So you build these

things up. What if I had a drug like all

transretinoic acid which basically what

it does is it takes and actually adds

ubiquitin onto this fusion protein. When

you ubiquitinate something often times

it tells proteosomes which are things

that break down proteins to say oh I see

something. Let me eat it. And it goes

through and it rips that thing apart.

Now you don't have any of the PML or R

alpha. If I don't have this, is it going

to be able to put a differentiation

block anymore? No. Guess what? These

things differentiate. And when it

differentiate, it actually can, funny

enough, if you give this sometimes it

can cause differentiation syndrome where

you make too many of these neutrfils,

but that's not neither here nor there.

It can make a lot of these neutrfils

which converts them. And so now you have

less risk of a lot of the problems that

comes with APL like DIC. And so that's

one of the benefits of this drug.

Intrathealcylup therapy with

methtoresate is really the stand hold

therapy as prophylaxis in patients with

the diagnosis of ALO. We can access

their cerebral spinal fluid which can

have contact with the meninges as it

flows across it via an omia reservoir.

So we can take and we inject the

medication into this right into their

cerebral spinal fluid right into a

ventricle or we can access their

cerebral spinal fluid via the lumbar

puncture and inject that medication

right in there as well. again it'll come

into contact with the meninges and it'll

get rid of a lot of those leukemic cells

or at least prevent them in a way from

forming there. So we often times do this

as prophylactic to prevent that with the

diagnosis itself. But if the patient

actually has infection which is

confirmed via LP or not infection but

the infiltration of leukemic cells we

have to give pretty high doses and a

little bit longer than desired. All

right SBC syndrome really a lot of the

times it comes with treating the

underlying disorder. So if you have a

tumor in that area, sometimes you may

have to just do chemotherapy um and some

radiation therapy and some steroids.

Usually the radiation and the steroids

are the big thing up front, but that's

going to be in a patient who doesn't

have severe emergent symptoms because

steroids are going to take some time and

so are the radiation therapy. If a

patient has high ICP or lingial edema

with respiratory distress, we ain't got

time to do that. We got to put a stent

in and keep that thing patent so we can

get blood flowing in. So often times

we'll put a stent in to just keep it

open and then we'll hit them with that

chemo, radiation, steroids to kind of

debulk the tumor and decrease it in size

so we have less compression. You're

treating the underlying disorder that

way. So that's a lot. So how do we kind

of put it all together? Well, if I said

that I got a patient who comes in with

luccoasis, what do you do up front?

Well, luccoasis, I'll do hydroxyhea

first, right? Especially if that white

count's really high. It may take some

time. So what do I want to add on?

Especially if they're really

symptomatic, I want to add on luciferis

because it's going to rapidly drop that

white count, reduce the further disease.

If I hear menial leukemia

prophylactically with the diagnosis of

ALL, I do intratheal chemotherapy,

right? But if they end up with a

diagnosis from an LP and they have

menial leukemia symptoms, I got to do

high high doses. If I SVC syndrome, I

just want to know are is it an emergency

with high ICP, lingulade edema,

hypotension. If it is stent, if it's

not, then what do I do? I say, okay, I'm

just going to go ahead and get them

ready, schedule them with radiation

oncology, get them some chemotherapy,

but particularly radiation therapy and

steroids along with chemo. shrink the

tumor and that should help with that

process. All right. If I hear that the

patient has DIC, I'm gonna support them

the best I can. If they have platelets

that are less than 50,000 and they're

bleeding, I'm going to give them a

platelet transfusion. If they have

hemoglobin less than seven, I'm going to

give them a packet cell infusion. If

they have high PTT, PT and they're

bleeding, I'll give them FFP. But again,

a lot of it's supportive. But if they

have APL, I have a specific treatment

that's all transretinoic acid. And then

lastly, if a patient has tumorlyis

syndrome, we want to know is it acute?

So, do they have the puke calcium

symptoms? If they do, IV fluids to

really reduce a lot of further kidney

injury, maintain good uimmia, and what

is the one that reduces uric acid after

it's already formed? Raspberase. All

right. And then after that, you can

again say, okay, the patient I given

them raspicase, but they unfortunately

they it sustained so much damage to

their kidneys and they ended up with

hypercalemia. they ended up with

worsening acidosis. They ended up with

hypervalmia and uremic symptoms. What do

you do? You dialize them like you would

any AKI patient that progresses that

way. But if it's a prevention, this is

not a patient who has acute tumors

syndrome, but they have a high pre uh

like a high risk or a probability of

developing that, you do IV fluids to

keep them euimmic, but you give alopurol

to decrease the formation of the uric

acid if it forms. Okay. So, let's move

into the actual treatment of the

underlying disease. Treating leukemia

involves obviously chemotherapy. And so

when we talk about acute lymphoplastic

leukemia, obviously it comes with its

plethora of complications that we talked

about managing, but we also have to

consider the treatment of the actual

underlying disease. And so when we think

about this, we think about something

called the CAD regimen. And so this is

really consisting of a couple different

chemotherapeutic agents. One is going to

be cycllophosphomide. The other one is

venristine. A is adriomyc also sometimes

referred to as docar rubicon and

dexamethasone which is a type of

corticosteroid. And so we're basically

giving these to kind of reduce a lot of

those leukemic cells in the bone marrow

especially if that patient does not have

a 922. What's the most common for acute

lymphoplastic leukemia? If it's a

chromosomal transllocation it's 1221.

Right? So this is going to be the CAVAD

regimen for most of those patients.

However, if the patient does happen to

have cytogenetics that support the 922

transllocation, we actually target the

BCRABLE which actually targets your

tyrroscen kinise receptors. And so we're

going to give them tyrroscen kinise

receptor inhibitors and that is going to

be things like a mat nib per se u and

any of your nibs. Those are going to be

the ones that are going to be targeting

that bcable fusion gene. All right,

particularly at the tyrroscen kinus

receptor point. Now obviously with the

goal um of that the disease is that you

have a hemocytoblast or a myoid stem

cell or lymphoid stem cell with acute

leukemas that are not differentiating

and they're just building up. And so

what if we replaced a lot of our stem

cells, our hemocytoblast or the actual

lympoid stem cells with normal stem

cells. And if we replace those normal

stem cells, they won't have these

genetic predispositions with the 1221,

the 922, the tricom 21, all of these

mutations that they've encountered.

You're giving them normal stem cells

that can differentiate and proliferate

into normal red cells, normal white

cells, normal platelets, etc. All right,

that would be the goal, but we only do

this in patients who really have that

high risk. They're they're basically on

chemotherapy and they potentially are

suitable for getting a bone marrow

transplant. Now with acute milo

leukemia, it's really citabine and donor

rubicon are going to be the drugs of

choice that we will actually target to

kill these leukemic cells. Now all

transretinoic acid is the really

important one that I talked to you guys

about in DIC. The reason why is you're

giving them supportive treatment but

you're treating the underlying disease

with all transretinoic acid. We also

there's been a lot of literature that

suggests using arsenic triioxide in

combination. This is another drug that

you can give. So again the kind of

question that you'll get on treatment of

acute milo leukemia is probably going to

be more pertaining to this one. All

transinoic acid is really really helpful

but there is becoming more literature to

support the combination of both of these

especially in those high-risisk patients

with APL. Again the concept behind this

is that again you're trying to remember

that with that 1517 you're getting that

fusion gene. And they're getting that

fusion ankop protein and that puts the

block on differentiation. If you give

them these medications like atra ultrans

retinoic acid it ubiquitinates this

fusion protein which kind of sets it up

to get degraded by proteosomes. Arsenic

triioxide can also help in that process.

But if you get rid of the PML raw alpha

fusion protein you basically say hey no

more differentiation block and now the

cells are allowed to proliferate and

differentiate and you now have normal

neutrfils. And that's the goal. Now

lastly, as with again any acute

leukemia, replace the stem cell because

if I can replace that myoid stem cell

with a normal stem cell that doesn't

have mutations or any kind of chemo

radiation that damaged it or myop

proliferative neoplas or miloisplastic

syndrome that are present. I'm giving a

normal stem cell that's capable of

differentiating into our normal types of

granularytes. And that's the ultimate

curative goal. Again, you're doing this

in patients who you're treating with

chemotherapy and maybe they're not

getting a little bit better. They're

high risk of continuing to get worse if

you don't kind of do something if they

have the proper candidacy and they're

fit for a transplant. So, my friends,

that covers acute leukemia. I really

hope that you guys liked it. I really

hope that you enjoyed it and learned a

lot. And man, I love you guys. I thank

you guys. And as always, until next

time.

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