Cram The Pance - S1E35 Leukemia

Episode Date: August 24, 2021

Leukemia review for your Pance, Panre, and Eor's. ►Paypal Donation Link: https://bit.ly/3dxmTql  (Thank you!)--- Support this podcast: https://anchor.fm/scott--shapiro/supportBecome a supporter of this podcast: https://www.spreaker.com/podcast/cram-the-pance--5520744/support.

All right, so let's learn about leukemia today. We'll make this nice and quick and just focus on the things that you really need to know. Thank you as always. You guys are the best. You leave the nicest comments. I really do appreciate that. So thank you so much for that. If you haven't checked out the YouTube channel, please do.

It's cram the pants under on YouTube. And you can have some nice visuals to go along with some of the stuff I'll go over today. So leukemia, as we know, is a progressive malignant disease of the body's blood forming organs and cells. There's going to be an abnormal proliferation and development of leukocytes and their precursors. So to put it simply, leukemia is white blood cell cancer. That's what the word leukemia broken down means. It comes from the Greek word, glucose, which means white and hama, which means blood. So white blood cell cancer.

There's a couple of different classifications. It's classified as acute or chronic by the degree of cell differentiation, so the cell age. So that's your acute first chronic, so AML versus AOL and CML versus CLL. And then it's classified by the predominant cell involved, so either myloid or lymphoid. your ALL and CLL versus your AML and CML. And of course, there's four different subtypes, acute lymphoblastic leukemia, acute myloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia. You're going to hear a bunch of variations in those names.

Acute lymphoblastic is also known as acute lymphocytic leukemia. Acute myeloid leukemia is also known as acute myelogynos leukemia, but just some variations, meaning the same thing. So a couple tips or just reviews before we get started of things that will just help it make a little bit more sense. So the first tip, more of like an anatomy review, if you see it's a myloid or myelogynosukemia, so AML or CML, you want to know where that's coming from. So if you're looking at AML, you're going to, you're looking at the cell line and specifically you're looking at myeloblasts. So the, the myloid cell line turns into your granulocytes or

your xenophils, your basophiles, monocytes, rithorocytes, et cetera. But when you're in the acute phase, you're basically looking for a disease that's involving the myeloblast, like the baby form of those cells. Later on in chronic CML, you can see an increase in any of those granulicytes later down in the line. So you can see your eocinophils, your basophils, but generally it's going to be predominance of your neutrophils when we're talking about CML. So granulocytes, any of one of them, but neutrophil predominance is generally what you'll see. Now when we're talking about lymphocytic, AOL, you're going to see obviously your lymphocytes. If we're talking about it, acute phase like an ALL you're going to be looking at your lymphoblast and then with CLL you're going to see lymphocytosis so an increase in your B cells your T cells your natural killer cells your NK cells any one of those can be increased most of the time it's your B cells but again those are the cell lines that are involved you see have a general idea when we talk about some of the things that you're going to see on bone marrow biopsy and your CBC and your smears and things like that the other tip I have for you more of a tip rather than an anatomy review is if the leukemia has an M in the

middle. So the AMLs, the CMLs, if it has an M in the middle, the patient is most commonly going to be middle age. So patients are generally going to be in their 50s and 60s with AML and CML. So if you see an M in the middle, think middle age. And then if the leukemia has an L in the middle, like in CLL, in ALL, you're going to think extremes of age. So either really old or really young. So we should be thinking as soon as you see that L think little, like in ALL, which is little kids, or L stands for lung and the tooth like in CLL, because that's most commonly diagnosed in patients in their 70s. So if you see CLL or AOL, think older young,

and then I'll go over some other ways to remember those. But if you see either one of those, you're thinking extremes of age, you see the M, like an AML and CML, think of middle age. All right, so let's go into each individual type of leukemia. I'll give you some ways to remember the high-yield stuff. So let's start with acute lymphoblastic leukemia, also known as acute lymphocytic leukemia.

So this one has an L in the middle. So we know it's going to be extreme of age. We know they're either going to be little or long in the tooth. I'll give you a way to remember which one it is in a second. So acute leukemia, this is an acute leukemia of the lymphoid precursor cells in the bone marrow, which we went over before. B cell is going to be your most common subtype in about 85% of cases. And then this is important. This is the most common childhood malignancy.

This is very important. If you have a vignette and it's a child and you suspect leukemia, it's going to be ALL. Remember, it's very important. The way that I used to remember this is, I don't know if you've heard, there used to be a soap opera called All My Children, right even into like the 2010s or so, so you should have maybe heard of it. It was pretty popular. Anyways, All My Children, ALL, All, and then My Children. So remember most common childhood malignancy.

So if you can remember all my children, you remember that ALL is the most common childhood malignancy, and that can help you remember that. And remember, of course, AOL can be seen in adults as well. well but we're talking about the most common things because that's what you're going to get on your vignette. So if you see ALL be thinking children. Clinical manifestations on all of these is a little bit of an overlap. A lot of times you'll see similarities. So this isn't necessarily very high yield, but you should be aware of some of the different things you'll see.

With ALL, there's really five clinical manifestations that are going to be present in most children that have this, at least one or more of these manifestations. So five things you need to be aware of. The first one is hepatomagaly or splenomagaly. So this is the most common clinical manifestation or physical exam findings in children with AOLL. About 64% are going to have epitomegaly on presentation, and 61% will have splenomagely on presentation. Second one you should know about is lymphadenopathy, seen around 50% of children. Fever is the third. So this can either represent a constitutional symptom of leukemia, or it can be caused by a secondary infection from the compromised immune system.

Either way, around half kids are going to have a fever at the time of diagnosis. Human toulogic abnormality, so this is kind of broad, but you can see patechiay, prepara, these are manifestations of anemia. Or you can also see manifestations of anemia, so like fatigue and pallor. And then finally, musculoskeletal pain. So they may come in limping, they don't want to bear weight. Less common than some of the other manifestations, but it's still seen in around 40% of kids with AOL. The bone pain, of course, is due to the proliferation and the bone marrow.

So the way that I used to remember the clinical manifestations for ALLL is I remembered ALL stands for anemic, lumpy, and limping. So anemic, of course, is those hematologic abnormalities, the purpura, the tikiipelor. That'll kind of help you remember those. You remember A stands for anemic. L stands for lumpy because remember lymphadenopathy, splenomagally, hepatomagally, they're lumpy, wherever you're palpating. So the lymph nodes are swollen, the spleen swollen, the liver's swollen. So lymphadenopathy and hepatomagely, remember lumpy. And then finally, limping is the last one because remember that musculoskeletal pain, they may come in limping or not wanting to bear weight.

And then, of course, remember, fever is the only part that's not in that mnemonic. All right, so diagnosis, we're going to be doing a CBC on any patient we suspect of leukemia. So we start with our CBC with diff. We're going to see pancytoppenia. That means the whole CBC is effed up. Your platelets, your white blood cells, your rub blood cells, everything's effed up. So pancytopinia is what we're going to see. anemia thrombocidopinia is going to be the most common to see and then you'll see white blood cell

quote unquote derangement so i say that because the white blood cells will likely be high around 50 percent of patients are going to have an increase in the white blood cells but the white blood cells can actually be normal or low in aOL so really the key is the anemia and the thromocyopinia and then just remember your white blood cells are likely going to be off whatever ways that are off They may be high, low. They may be normal. Just know that they're going to be deranged, is the way I say it. All right.

And then we have our best test. That's going to be your bone marrow biopsy. What you're looking for in bone marrow biopsy is over 20% lymphoblast. That's your key, greater than 20% lymphoblast. That's going to be in the vignette. That's how you're going to know. This is AOL. You'll see the lymphoblast on peripheral smear initially, but you always confirm it with

the bone marrow biopsy and you see over 20% blast. Remember, those are your immature, your baby cells. You see over 20% of those you know you're dealing with an acute leukemia. And in this case, you're looking at lymphoblasts because it's ALL. So we know acute lymphocytic leukemia when we see that. Now treatment, I don't think you should remember about the specific agents. Just know you're going to be using chemo. So ALL is really responsive to chemo.

Again, don't worry about the different types. There's been a Christine. There's corticosteroids you use with that. A bunch of big names. Don't waste your time on it. It's not high yield. You're not going to get tested on it. The only thing I think you need to know about treatment for patients with AOL is that you need to

prophylax their CNS. So CNS preventive therapy that's done with intrithecal methotrexate. So ALL can infiltrate and hide in the CNS. Because of this, you have to prophylax the CNS. You do this with intrithel methyl methotrexate. And before they started CNS prophylactic therapy, around 80% of children's children that had AOL, that were in complete bone marrow remission, would have a lot. relapse with leukemic meningitis.

So they have to have this CNS prophylaxis with intrithecal methotrexate. So that may come up. I don't think they're going to ask you about specific agents for the chemo, but you need to know that you do need to prophylax their CNS. So remember again for ALL, remember all my children, most common childhood malignancy. Remember, AOLL stands for anemic, lumpy, and limping for clinical manifestations. Remember, you're going to see those 20% or greater lymphoblasts or over 20% lymphoblasts and bone marrow. biopsy and then remember you use chemo and prophylax the cns that's really all you need to know for

all right so moving down the line with our acute disorders we'll go on to acute myloid leukemia AML so it has an M in the middle we know they're going to be middle age so this is the most common type of acute leukemia in adults now there's subtypes of this there's a few different subtypes but really there's only one super high-yield one that you need to know and waste your time on it's the only subtype you need to waste your time on with AML that's going to be acute promylacidic leukemia, also known as APL, which is the letter abbreviations for it, also known as the M3 variant. You only need to know three things about this subtype. Miloproxidase, hour rods, and vitamin A, vitamin A, also known as all transretinoic acid. So number one, myloproxidase. If you have APL, acute pro myelacytic leukemia, it's going to stain positive for myeloproxidase.

So that could be in the vignette. Second one, this is the highest yield part of this, probably of all the leukemia's top three. I'd say. Our rods. So these are these needle-shaped structures that stick out of the cytoplasm. They may show you a picture, like a microscopic finding, possibly. You need to know this. As soon as you see hour rods right away be thinking acute promylacidic leukemia, which is a variant of AML. The way that I have for you to remember this is hour rods, instead of hour rods, remember A-Rod for hour rods. And A-Rod, I'm sure most of you know. I know nothing about baseball, but I know who A-Rod is. I know it's Alex Rodriguez. He dated J-Lo. He played for the New York Yankees. It's

about all I know about baseball. So remember, A-Rod's stands for A-Rod. Think of A-Rod. He played for the New York Yankees. Where did he play in the big Apple, APL, acute promylacidicic leukemia? So again, you see HourRods. Think A-Rod played for the New York Yankees and the big Apple, APL, acute promylacytic leukemia. That's the way I used to remember hour rods. Hopefully that helps you. And then the third thing you need to know about APL, variant of AML, is that you treat this variant with vitamin A, in addition to chemo. So they need treatment with vitamin A, also known as all trans-retinoic acid. So again, acute promylocytic leukemia, no myeloporoxidase positivity, hour rods,

and then vitamin A for treatment. Clinical manifestations, patients with AML are usually going to present with symptoms related to complications of the pancytoppenia. So anemia, neutropenia, thrombocytopinia, most common symptoms you're going to see fatigue. So presents in the majority of patients, it may proceed the diagnosis by, you know, number of months they may have pallor weakness this is related to the anemia they may have infection which is caused from the neutropenia all of the lumpy symptoms that we talked about in a l halle hapate omegaly splenomagely lymphadenopathy

they're rare in a ml now our diagnosis again we're gonna start with our CBC with diff we're seeing pancytoppenia like we saw in a L so thromocytopinia anemia neutropenia thrombocytopinia is really the most common finding you'll see on CBC so low platal account you're gonna see in most patients with AML. Now bone marrow biopsy, we know this is an acute leukemia, so we know we're looking for blast, specifically over 20% myeloblast. It's an AML, so acute blast, and then mylogenus or myeloids, so we know we're looking at myelblasts. So just like in AOL, you do a smear, you can see those circulating myeloblast, but you always do a biopsy to confirm. Again, what

you're looking for is over 20% miloblast. That's going to confirm the diagnosis. And then remember if it's the APL subtype, you may see those little pink needles poking out of the cytoplasm, which is the hour rods. Now, treatment, chemo, it's about as far as you need to remember. The only additional thing you need to know about treatment is remember if it's that APL, that M3 variant, remember you're going to add on that vitamin A, all trans-ranoic acid. So what you need to know for AML, remember, acute molylycytic leukemia, APL, you're going to see hour rods treat with vitamin A, bone marrow biopsy over 20% myeloblast, and then remember it's the most common type of acute leukemia in adults. All right,

Moving on to our chronic, chronic lymphocytic leukemia. Of all the leukemia, this is probably the one you need to know the least about. There's only really a few things I think you should know about this one. So first, this is a mature B cell neoplasm that involves a progressive accumulation of monoclonal B lymphocytes. So it's a fancy way of saying we got a crap load of defunct or incompetent B cells. CLL, this is going to be an old patient. Median age of diagnosis is 70. it's mainly a disease of older adults increasing age is one of the main risk factors remember

the L and CLL stands for long in the tooth so in your vignette be looking for an older patient 70s or 80s that's important that's how they're going to give you it on the vignette remember they're going to give you the most common manifestation not the oddball of some younger person so CLL remember long in the tooth this is going to be an old person clinical manifestations the main one you need to know is that they very well may be asymptomatic the majority of patients with CLL are going to feel completely fine, and it's just going to be an incidental finding on a routine CBC displaying lymphocytosis. So a small number of patients may have those B symptoms, like fever, night sweats, fatigue, around 5%. And then in AOL, CLLL patients are also going to be lumpy. So lymphadenopathy,

splenomagaly, hepatomagaly are all possible. Really, those are the main things you need to know. I would just focus on the fact that a good portion of these patients are going to feel completely fine, and you're just going to find this incidentally on your labs. Now, diagnosis, of course, we start with our CBC with peripheral smear. There's two key things you need to know for the diagnosis when you do that CBC. And it's going to be lymphocytosis and smudge cells. So first, absolute lymphocytosis, that means over 5,000. This is the most important laboratory abnormality found in CLL is lymphocytosis in the peripheral blood.

The threshold for diagnosis is over 5,000, but a number of patients with CLL will have counts as high as 100,000. So really high lymphocytes. Then the second high yield thing is something called smudge cells. So this is a hallmark finding in CLL. All smud shells are a lab artifact. There are lymphocytes that are smeared out in the process of being spread on the glass slide. You know when you do microscopy, you have that little glass slide and you put the little cover slip over the top. What happens is these CLL cells, they're more fragile than normal lymphocytes and they literally smudge.

So it seems like something minor, but it's one of those things they all. always mention in the vignette. So if you see smudge cells, I think CLL. And the way that I used to remember that is remember that CLL stands for crushed little lymphocytes. So remember, smudged cells is smudged lymphocytes. Remember, CLL stands for crushed little lymphocytes. And that helps you remember smudge cells. Okay, treatment, very easy. If they're asymptomatic, you're just going to observe. If they're older, generally over 65, they're not having any symptoms. You're just going to observe these patients. CLL in an older patient is often something they're going to die with rather than from. Similar to prostate cancer and older patients, a lot of times you're just going to observe these patients. If they are symptomatic, they're younger, you can use chemo. Stem cell transplant is another option for your younger patients, which can potentially be curative. But a lot of times we're just going to observe these patients. So again, the things that you need to know, remember that they're going to be old, they're going to be lumpy, they're going to have lymphocytosis, they're going to have smudge cells, and you may very well just observe these

patients. All right, let's move on to our last. That's going to be chronic mylop. or myeloid leukemia. So a few high yield things in this. So listen up. All right. So first, CML has an M in the middle. So we know this patient is generally going to be middle age, 50s or 60s. This is a myeloporoperative neoplasm with uninhibited proliferation of granulocytes. So the hallmark of CML is uncontrolled production of mature granulocytes, predominantly neutrophils. So remember that. It can involve your basophils, your eocinophils, your other granulocylus. but the main thing is that you're generally going to see a crap ton of neutrophils in this type of leukemia. So remember that.

Patho, this is about as high yield as it gets right here. So probably on the same level of our rods. So in CML, you are going to have a reciprocal translocation between chromosomes 9 and 22 that gives rise to this abnormal chromosome called the Philadelphia chromosome. So 922 translocation in Philadelphia chromosome. you have to know that's associated with CML. It's super high yield, committed to memory. If you forget everything else about CML, just remember Philadelphia chromosome, 922, translocation.

Of course, I'll give you a way to remember it at the end. Clinical manifestations, there's going to be a few different phases for CML, your chronic, you're accelerated, your blast crisis. Manifestations are going to be different for each stage. Don't memorize the stages. Just know that the manifestations can vary. 50% of patients are going to be asymptomatic, so again, similar to our CLL.

All depends on what stage they're in. And then the most common thing you're going to see is splenomaguline, about 75% of patients. So very common. They may also have left upper quadrant pain or fullness due to this. And then just some other nonspecific symptoms, fatigue, weight loss, fever. Diagnosis, we're always starting with our CBC. We're looking for two things. So first, we're looking for leukocytosis.

Your white blood cell is going to be very high, approximately 100,000. So really elevated. But then the key here is that you're looking for neutrophilia. So the differential is going to show elevated granulacetic cells, neutrophils, mesophils, eocinophils, but most of the time, and on the vignette they're going to give you, you're going to see very high neutrophils. So predominance of neutrophils. So remember, CBC is going to show you leukocytosis, but it's going to have a neutrophil predominance.

That's really the key, not only for your vignette, but, you know, when you're actually treating patients, if you see this really elevated neutrophil count, really high white cells, you should be thinking the possibility of a diagnosis like CML. It should be on your differential. Now, treatment, this is probably the only one where I feel like you really need to know the treatment option. Treatment for CML is going to be a class called tyrosine kinase inhibitors, particularly a matinib. So this is the only one, this is really the only type of leukemia where I feel like you should know the drug being used. And it's unique in CML. So let me explain why.

So going back to that Philadelphia chromosome we talked about earlier, that 922 translocation. So this translocation is caused from a tyrosine kinase over a. expressing. So wouldn't it be nice if we had a drug that specifically targeted that overexpression, that translocation? That's exactly what a matinib is. It was developed in the late 90s specifically to target the overexpression scene in CML. The drug was literally made just for this. And that's why it's so important to know. So matinib was the first targeted therapy we had for cancers. It was the first one that ever came out. It's still a good drug. There are some newer tyrosine kinase inhibitors, but most of the time you're going to start with a matinib and you need to know if you have a

question of vignette that has a patient with CML. Remember, you should be looking for a matinib. That's normally what you start with. Once that fails, you switch to some of the newer agents, but normally you start there. All right. So CML, there's a few high-yield things in it. This is the way I have for you to remember it. It's a very short story. So what I want you to remember is Tyrone was a country music lover and he was excited to go to a country music concert in Philadelphia. It was on 9-11. Unfortunately, tragedy stuck that struck that day and the concert was postponed. Days later to 922. So let me say that one more time since I kind of messed that up. So Tyrone was a country

music lover and was excited to go to a country music concert in Philadelphia on 9-11. Unfortunately, tragedy struck that day and the concert was postponed days later to 922. So Tyrone. When you see Tyrone, think Tyrocyne Kinase Inhibitor. Remember, that's your first line therapy. Matib in particular. So Tyrone, Tyrosine Kinase Inhibitor was a country music lover, CML. So that helps you remember for CML, country music lover. It was excited to go to a country music concert in Philadelphia, Philadelphia chromosome. On 9-11, unfortunately, tragedy struck that day, and the concert was postponed days later to 9-22, 9-22 translocation, Philadelphia chromosome.

So that's how you can remember that. Just remember a guy named Tyrone, likes country music, went to a concert in Philadelphia, supposed to be on 9-11. We all know what happened on 9-11, postponed later to 9-22. All right. So that is leukemia. Those are the main things you need to know. I wouldn't really stress anything else.

Let's go and do five quick questions. Question one, a 57-year-old male presents to the office today complaining of fatigue and weakness over the past few months. On exam, splenomagely is noted. A subsequent CBC and bone marrow biopsy are performed, and it is discovered that he has chronic myelogenous leukemia, CML. What class of medication will this patient likely be started on? We'll hopefully remember since we just did that one. That is going to be tyrosine kinase inhibitors, amatinib in particular. So remember that's CML, country music lover, Tyrone, country music lover, Tyrus and Kinesinhibitors.

All right, question two. A seven-year-old boy presents to the office accompanied by his mother. She states he has been excessively tired for several weeks and has had a persistent fever that just does not seem to be getting better. On exam, ekemosis is noted on both upper and lower extremities as well as hepatomagally. A CBC is performed that shows pancytopenia. Bone marrow biopsy is ordered, which displays over 20% lymphoblasts. In addition to starting chemotherapy for this patient, what additional treatment option is necessary for the likely diagnosis? So he has ALL, evident by the lymphoblast, the clinical presentation, the CBC showing pancyotophenia.

Mainly it's the 20% lymphoblasts and his age, of course, a seven-year-old boy. We know we do chemo, but then we also know the additional treatment option is going to be CNS prophylaxis. Again, remember, that's with intrithecal methotrexate. Question three, a specimen is sent to the lab for analysis. When the specimen is placed on the slide and a cover slip is applied, on visualization, these cells appear to be smudged or damaged. Which type of leukemia most commonly displays this type of abnormality? So remember, that is going to be CLL, chronic lymphocytic leukemia.

Remember, CLL stands for crushed little lymphocytes, your smudge cells. Question four, the Philadelphia chromosome is caused from a translocation between what two chromosomes? So remember, that is going to be 9 and 22. Remember the concert in Philadelphia got delayed because of the translocation. tragedy on 9-11 to 922. Question 5. The presence of hour rods and myeloproxidase positivity should raise suspicion for which leukemia subtype.

That is going to be acute pro-mylocytic leukemia. Remember, A-Rod, hour rod plays in the Big Apple, APL acute pro-mylacidic leukemia. Remember, that's a subtype of AML. All right. So that was leukemia. Hopefully that was helpful. Thank you so much, guys. As always, for everything, all the support.

I really do appreciate it. Good luck on your pants, your panery, your EORs, and good luck in PA school.