WK 3B leukemia lymphomas and myelomas

This week, we're looking at the first of our pathologies for the white blood cells, leukinias, lymphomas and myelomas.

Now, not just for every year I teach this module, there's usually at least one person in the room who has either had leukinia themselves, has a family member who either has or has had leukinia or knows someone through their friendship circles who've been affected by leukinia.

So at no point do I want to cause upset, but we are going to talk about some very difficult concepts as we go through in terms of diagnosis, in terms of treatment and in terms of the prognosis.

So just bear that in mind, I don't want to upset anyone, but some of what we cover will be challenging.

Okay, all right, so leukinias, myelomas and lymphomas, we are recording learning objectives.

You should be able to describe and differentiate between leukinia and myeloma, then three different conditions.

We're going to look at several different types of leukinia, so you should be able to describe and tell me about the differences and similarities between the different types of leukinia.

The different types of lymphomas, and then we've just got one type of myeloma.

When we look at the pathology, we think about the pathophysiology, so their normal physiological role for myeloma cells.

The pathophysiology is that function when it's abnormal, signs and symptoms for each of the different conditions, how it's diagnosed, how it's treated and the prognosis. A lot of the steps and resources come from Cancer Research UK.

Fantastic website, reliable in terms of the statistics for how common different conditions, different cancers are. So if you have some extra time, you might want to explore their website and look at some of these conditions in a bit more detail.

Mapping on to our standard module learning outcomes, it's on to number two, I've folded it. So the pathophysiology, the pathophysiology, signs and symptoms for leukinia lymphoma myeloma. Let's start with an overview, the differences between them.

What are these three conditions? So leukinias are cancers of the white blood cells.

Lymphoma is cancer of the lymphoid tissue, and we introduced lymphoid tissue a week or two ago. The different types of lymphoid tissue like our lymphos, our spleen, the thymus, payers patches in the gut, lots of different lymphoid tissues, so lymphoma is cancer of the lymphoid tissue.

Myeloma is a more specific type of hematological blood cancer, it's cancer of the plasma cells.

So plasma cells are our antibody producing B cells, the antibody factories, and this is a cancer of those.

The leukinias, the cancers of the white blood cells can be divided into four main groups that we're going to cover this afternoon.

So we've got acute myeloid leukemia, abbreviated to AMM, acute lymphoblastic leukemia, ALL, chronic myeloid leukemia, CML, and chronic lymphoid leukemia, CLL.

From the picture we can see what's happening with the leukinias.

Here is our cartoon of a blood smear, usually in the normal sample we should see lots and lots of red cells and just a few white cells.

In leukinias, cancer of the white blood cells, we get uncontrolled proliferation of the white blood cells, so more white blood cells than there should be.

So four different types of leukinias.

For the lymphomas we've got two different types, we've got Hodgkin's lymphoma and non-Hodgkin's lymphoma.

Hodgkin's and non-Hodgkin's, as I said, cancer of the white blood cells.

So we're talking a lot about cancers. To understand cancer we need to think about how normal cell cycle is regulated, how cells normally divide and reproduce at a normal regulated pace. Not too fast, not too fast, not too fast, not too fast, not too slow.

So normal cell proliferation, proliferation meaning producing more, normal cell proliferation is regulated by growth factors.

Some of those growth factors are products of proto-oncogenes, proto-oncogenes.

If we think about a car, a proto-oncogene is like the gas pedal. So the products of those proto-oncogenes tell that car to drive forward.

So from proto-oncogenes tell the car to proliferate, to travel forward and to divide. Tumor suppressor genes, on the other hand, these produce products which act like a brake pedal. So in a car they act like a brake.

Here they're depicting a brake that is like a parachute type brake. So we've got the gas pedal pressing the accelerator and we've got brake pedal stopping us.

And these different gene products, so gene products of proto-oncogene and tumor suppressor genes balance each other out so that the cell divides at a normal regular rate.

Not too fast. What happens in cancers, so in this case we're talking about immunological cancers, blood cancers, we get some sort of genetic mutation within a single cell.

So one cell has its DNA, its genetic material, mutates and that can happen either in the bone marrow where the white cells are working.

And those mutations tend to be in either these proto-oncogenes or tumor suppressor genes. So if we have a mutation in the gas pedal, the proto-oncogene, it becomes an oncogene.

And that's like jamming the accelerator on. So someone is pressing the accelerator on that car and not taking their foot off the pedal. That car is just going to keep driving until it smashes into a brick wall. So proto-oncogenes become mutated to oncogenes and then they just carry on driving until they hit the brick wall.

Tumor suppressor genes on the other hand, when we get mutations in the brake pedal, it's like we've lost the brakes.

So we're not driving any faster, it's not that someone is pressing the accelerator, it's just that the car can't stop.

And again, the result, it smashes into the wall. So that causes cancer.

As you know, with mitosis, we get cell division, cell division, cell division. If those have got that initial dividing cell, one cell becomes abnormal, genetic mutation, then it will give rise to what's called a focal population.

All of the descendants from that cell will be identical to the original.

So we start off with one cell that went wrong, but by the time it's divided, lots of times we now have a cluster or a clump of cells all identical, all wrong.

So this is known as a clonal population. After we think about cancers in this kind of way, we think about them as being really aggressive and fast moving and some cancers up.

But lots of cancers are not fast and aggressive.

The gas pedal, when we put the gas pedal on, that might be an aggressive one, or it might just be that we're not going any faster than normal, we're just not stopping, we're not easing off the gas.

Likewise with the brake pedal, we weren't travelling any faster than usual, we just haven't got any brakes. So we could be travelling on at two miles an hour, but we're just never, ever, ever going to stop.

So it just keeps going and going and going. Often cancer cells are sick, these are not healthy cells, they've got mutations in them. So often they are in fact dividing slowly, but they just don't stop, they keep going and going and going. So we get more and more and more and more, division, division, division, until it takes over.

Are we happy with cancer? Yeah, well obviously we're not happy with cancer, but with our understanding of it.

We'll talk today a lot about incidence and prevalence quite a bit, so let's make sure we're all clear on what these terms mean, terminology.

Imagine we've got a big beaker, in the beaker we've got, each of these balls represents people diagnosed with a certain condition, so the prevalence, all the people within the beaker, this is our number of people with the condition and that's our prevalence. So when we talk about the prevalence of leukemia, that would be the number of people who currently have leukemia. When we look at incidence, incidence is the number of new cases coming into the beaker in a given time period. So the number of new cases in a given time period, or the number or percentage of the population at risk of developing it.

If you're coming into the pot, you've got a higher risk of developing that condition.

The only way we can leave the pot is either by being cured, that's a good way to leave the pot, so we no longer have it, we're no longer part of that prevalence, but the other way people leave the pot is by dying. So if we die from the condition again, we're no longer as fast as part of the statistics of people who currently have the condition, we're not in that prevalence count anymore. So instance coming in, depth or curing going out, and prevalence, the number of people with the condition. Let's pass straight on in then to the first section. Leukemia isn't time for cancer of the white blood cells. So this is uncontrolled cell division of white blood cells and that's happening in the bone marrow. So white blood cells produced in the bone marrow, some of them then go elsewhere in the body to function or to finish material, but they're all produced in the bone marrow. What happens if we've got a specific type of white blood cell that's dividing, dividing, dividing, dividing, uncontrolled proliferation, is we will see a high count for that white blood cell type, but then that overcrowds the bone marrow. So the bone marrow where it's taking place becomes filled up with those clonal populations, identical copies of an abnormal white blood cell. And if the bone marrow fills up, there's not enough space for the normal function of the bone marrow, which is to produce all the blood cells, red cells, white cells, face them. So we get overcrowding and ultimately bone marrow failure. If we look at leukemia, this is still the most recent data actually on Cancer Research UK. Up at the top here, the most common cancer is still lung cancer in the UK affecting both men and women. Bowel is the next most common one for cancers that can affect men and women. Then you have the sex specific ones, so prostate for men and breast for women. Following those, pancreatic, unknown, esophageal, liver, bladder, central nervous system, non-Hodgkin's lymphoma and leukemia. So leukemia is, where is it on our list? It's the 12th most common cancer in the UK. Each year, around 10,000 people are diagnosed with leukemia within the UK. So just within the UK, about 10,000 are diagnosed each year. So if we work that out per day, it's about 28 people a day are diagnosed with leukemia and about 13 people per day die of leukemia. So this is something that is affecting a lot of people. Hence, in previous years, there's always been someone in the room who has either had it themselves or knows close family friends who've had it. So we've got these terms here, instance and mortality. Remember, instance is the number of new cases arriving. So we can express this as per 100,000 people. So 16.2 cases per 100,000 people. Mortality, 7.6 per 100,000. So after 100,000 people, 7.6 of them die of leukemia. It's the most common childhood cancer. So leukemia is the most common childhood cancer. And a lot of emphasis goes on to that in terms of children. It's horrible when any body of any age gets cancer, but it's very horrible when children become very, very poorly. So a common childhood cancer, however, it affects adults more. So although it's the most common childhood cancer, more adults have leukemia than children have leukemia. So it affects three times as many adults as children. Okay, so we've already said this is our key concept. So I put this slide in a couple of years ago following an exam question where lots of people couldn't even tell me the fundamental key concept. So I added an extra slide to make sure people really understand it. Leukemia, cancer of the white blood cells. So that means uncontrolled proliferation of the white blood cells. It's taking place in the bone marrow, the pelvis, the sternum, the heads of the femur, the ribs. So it can start anywhere in that bone marrow. We get lots and lots of one specific cell type. And then we have too little space, not enough space for all the other cells in the bone marrow. So overcrowding of the bone marrow. If we overcrowd the bone marrow, what's going to happen? Well, there's not enough space to make red blood cells. So we get anemia. There's not enough space to make platelets. So we get thrombocytopenia. There's not enough space to make other white blood cells. So we get leukopenia. Then we might have leukocytosis, high white cell count. Because we might have a really high amount of the abnormal white cell, high count of cytosis, but low count of all the other white blood cells. And remember the cell that we've got loads and loads of is a duct cell. It's not a fully functional, useful white blood cell. It's a sick, abnormal white cell. And we have really key concepts for leukemia, yeah? Good. What causes leukemia? Most of the time it's never known. So we've got certain correlations that are known. So things like people who've had chemotherapy for a different type of cancer, a previous cancer, that chemo, unfortunately, increases their risk of getting leukemia later. We've got things like exposure to radiation, exposure to nasty chemicals like benzene and somaldehyde. Certain genetic conditions can make the DNA a little bit less stable. So things like down syndrome. People with downs have a higher risk of leukemia. And then conditions like myelodysplasia. Myelodysplasia is like a pre-lukemia, a pre-lukemic state. But a lot of the time, none of these known risk factors apply. Think of a small child aged four, has leukemia. Have they been exposed to chemo? No. Have they had much radiation?

No. Have they been exposed to chemicals? No. Do they have downs? No. Do they have myelodysplasia?

No. So a lot of the time, it's just not known. And it's put down to being one of those things. And it's not fair. No one is saying anything that's fair. It sucks. It's rubbish. It's just sometimes what happens. The chemo said we have four different types of leukemia that I'd like to talk about today. So AML, acute myeloid leukemia, ALL, acute dysplastic, CML, cronic myeloid, and CLL, cronic myeloid. There are other types of leukemia, for example, things like hairy cell leukemia. But we're not going to go down those routes. We're going to stick with the main four. Hopefully by now you're recognizing this picture. So I've used it a few times. Richard used it. We can use this to look at the four different main parts of leukemia. Those of you who did the pathology module last year, this should be familiar to you, but I know not everybody took the knowledge. So the four main classes. The first one then are acute myeloid leukemia. Acute myeloid leukemia. So it's got leukemia in the neck. That means it's uncontrolled proliferation of the white blood cells. Myeloid means it's affecting the myeloid cells. So we know in this picture here on the left-hand side, these are all myeloid cells over here. And on the right, we've got the lymphoid cells. Now it tends not to affect platelets and red cells because they end up as being a nucleus. They don't have that genetic material once they've matured. So it does tend to be more an issue for the white blood cells. It's called acute myeloid leukemia. And the definition of acute is based on the percentage of blast cells. So to be an acute myeloid chemo, you have to have more than 20% blast cells in the blood or bone marrow. Blast cells are our immature undifferentiated cells. So up at the top here, we've got a myeloblast. We've got some pro myelocytes here. We've got a monoblast. These are all blast cells. Mega carrier blast, proerythroblast, lymphoblast. These immature ones up at the top here, blast cells. Blast cells are not yet fully differentiated. They haven't yet fully decided what type of cell they're going to be. We can often recognize them because they have a lot of nuclei in them. So the nucleus is very big. They sit in the bone marrow. They shouldn't be in circulation. So if we're seeing 20% blast cells in the blood when they should be. So the yellow up the left hand side here shows the cells that should be in bone marrow, not in blood. Only those level with the red blood label here. These should be found in the circulating blood. But certainly anything like a blast cell really should be only in the bone marrow. So if we have 20% or more blast cells circulating in the blood or indeed in the bone marrow, that's an acute leukemia. We also tend to see the acute leukemism coming on rapidly. So we can also describe it as acute in the sense that it's often a more medical emergency. It's a rapid onset. So we need to deal with it rapidly, quickly response. So that's AML. ALL, acute lymphoblastic leukemia. It's leukemia. It's uncontrolled proliferation of the white blood cells. It's lymphoblastic. So it's involving the lymphoid line. Plastic gives us a clue again to blast cells. It's acute. So more than 20% blast cells. Chronic myeloid leukemia. It's leukemia. It's cancer in the white blood cells. It's the myeloid line. And chronic means there's less than 20% blast cells. Instead of having lots of blast cells in the circulation, we get lots and lots of mature white blood cells. In this case, we're going to see lots of mature neutrophils or maybe basophils, eosinophils, or maybe monocytes. It's myeloid. So we get lots and lots of mature myeloid cells. The last one then, CLL, chronic lymphoid leukemia. Leukemia, uncontrolled lymphoration of the white cells. It's lymphoid. It's involving the lymphoid cells over there. Chronic, we get lots of mature lymphocytes. We don't have so many blast cells, so less than 20% blast cells. With the chronic ones, they're often slower progressing as well. They're often slower. And we see that changes some of the signs and symptoms that we see from the different leukemia. So diagnostically, to differentiate, it's all about the number of blast cells. Not the speed. It's all about the blast cells. But we can explain some of the symptoms through that speed as well. Okay. 30 seconds decompress. All right, clean your head. Have a little break. 30 seconds. Okay. So hopefully the basics of leukemia is pretty straightforward. Uncontrolled proliferation in the bone marrow. Take enough space, not enough space for all our other stuff. Okay. Let's now look at each of the leukemias in test. So the first one is our acute myeloid leukemia. Uncontrolled proliferation of white cells. It's a myeloid stem cell. And that's going to result in a lot of immature. So it's acute. So we get lots of blast cells. Lots and lots of immature white blood cells. Particularly the blast cells for our myeloid cells, the granular side and the monocytes. When we look at the epidemiology and AML of sex, people of any age. So anyone from little to old. But there is a brand new increased risk as we get older. So the median age for people who have AML is 60 years of age. And the peak age for diagnosis is 85 plus. So it's a condition more of older people than of youngsters. The incidence for the number of people getting diagnosed with it is 4.6 per 100,000. And we talk about AML as a single cancer. One type of leukemia. But it then can be further subcategorized. So it can be categorized into M0 through to M7. So you can have AML, category M2 or AML, category M7. Each of those categories have slightly different diagnostic criteria. And the treatment protocol would be different depending on whether you're an M0, an M3 or an M5. That will vary the treatment level. That's beyond what we need to know. So for my respect I don't want you to know about AML generally. And be aware that there are different types. But I don't need treatment protocols for each different type. Signs and symptoms then. So we've got these bands with us up on the board. What I'd like you to do is with a partner or a friend. Have a look at these and run through why you think we see each of these. So why in acute minor leukemia do we see fever? Why do we see anemia? What would be the signs and symptoms of that? So I'm going to give you just one minute to run through this. See how much you can get in our units. Okay, with a friend, off you go. Last 10 seconds. Okay. If we can understand why we see these signs and symptoms, we shouldn't need to remember them. Because we should just understand and then we can produce it in an essay if you were asked to describe the signs and symptoms of AML. So let's see if we can really understand it. Let's take a nice and easy one to begin with. Anemia. Why do we see anemia in patients who have AML? Because it's an issue with the blood. An issue with the blood, yes. So the red cells are getting crowded. That crowding is the key work.

Well done. So the bocca is overcrowded with these myeloid cells, which have copies of this rogue white blood cells. We produce, we produce, we produce. There's not enough space to make red cells. So we ended up with anemia. What are the signs and symptoms of anemia? We're in trouble if you don't know the signs and symptoms of anemia. So tiredness, exactly. So tiredness, pallor, tachycardia, shortness of breath, possibly headaches, dizzy. All sorts of signs and symptoms for anemia. What about neutropenia? Why do we have neutropenia? Overcrowding of the bone marrow. So we haven't got enough space to make the neutrophils. We might have lots and lots of copies of an immature blast cell for neutrophils, but we still haven't got any actual useful mature neutrophils, or not many. If we have low neutrophils, what type of infection are we most at risk of? Bacterial, well done. Thrombocytopenia, why do we have thrombocytopenia? Because of overcrowding, well done. So not enough space to make a mature platelet. If we don't have enough platelets, we get bleeding. If we get bleeding, we might see it as bruising. We might see it as speckles under the skin. We might see it as those bleeds. We might see all different ways we can see bleeding. DOC is a nasty, nasty, nasty condition. We'll cover later in the module. It's where you have too much thrombosis and too much bleeding at the same time. Patients will be in intensive care. It's horrifying. So we have a bit of anemia and neutropenia and thrombocytopenia. Pretty straightforward, yeah?

Good. What about malaise, fever and sweats? Why do we get malaise, which is just the word for feeling meh? Just feeling a bit rubbish. Why do we get malaise, fever and sweats? It's a bit of a transcription chart, because you have more of a lot of infections. So there is that side to it. So is the fever because we've got more risk of infections? Possibly. So we're trying to fight off bugs, pretending that we've resolved in fever. It might contribute to it, but it's not the main reason. What generates heat? Inflammation. So we're going to have lots of inflammatory effects going on as well. But what else will generate heat in the body? What kind of activity? Metabolic, such as? What's happening in the cancer? Division, division, division, division. Lots and lots of metabolic activity. So the body is using a lot of energy to divide, divide, divide, divide, divide. So we're going to use energy. Heat is created as a byproduct. We end up with fever. If we get fever, why do we get sweats? It's a response to heat. It's a natural response to heat. The body is trying to cool itself off. Malaise, feeling a bit rubbish, is because you're rapid. Your body is burning energy. It's creating all this heat, doing lots and lots and lots of activity. Not useful activity. But it's still doing stuff, so we feel knackered. Are we happy with malaise, fever and sweats? What about acute? Why do we call this one acute? Why is this one acute? What's the difference between acute and chronic? Blast cells. So we've got lots of the blast cells rather than the mature cells. The other side to acute is the rapidity, the speed at which the symptoms come on. So patients often get sick quite quickly and become critically ill. So it's quite a rapid onset, this one. Are you all happy with signs and symptoms? Ooh, let me clarify. Signs are things that the doctor detects. Symptoms are things the patient reports. So the patient might report, I'm short of breath. The doctor might measure and go, your heart's feeling not happy, are you? You might say, I feel hot and sweaty. The fever sticks. I'm not really a fever. The doctor put some signs from your tongue and says, you have a temperature of 39. You have a fever. So signs, doctor says, symptoms, patient says. Red flags, red flags. Red flags are symptoms that usually indicate something more nasty is going on. So red flags, if you went to see your doctor and they thought you had several red flags, they should be referring you on rapidly for further assessment. It's the symptoms that we look for that indicate something nasty might be happening. Now the red flags that we've got in these patients here are unexplained fever. Unexplained fever. If someone had a snotty nose and a chesty cough with fever, that's explained. They've got an infection. But fever without that infection. Night sweats. Sweating a lot at night. When might it be completely normal to sweat at night? Who, which people, sweat a lot at night? People having nightmares. People having nightmares, yeah. Who else? Menopause of women. Absolutely menopause of women. We get a bit hot and sweaty for safety at nighttime. That does not mean we've got leukemia. It's an explained night sweats. But unexplained night sweats. Unexplained fever. That's two red flags. The third one which is generally passed as the red flag is unexplained weight loss. Unexplained weight loss. You get unexplained weight loss when the body is using excessive energy. Divide, divide, divide, divide, divide, divide, divide. Why is there not weight loss on this list of symptoms? Why do we not see weight loss in these patients? What needs to happen in order for weight loss to occur? How long do you think we need to monitor the patient for? At least weeks, generally weeks, isn't it? You don't have to watch them for days, weeks, months, you're going to see weight loss. These patients are critically ill. They don't go from being in all the way to the Thursday, being in A&E on a Saturday, and being treated on a Sunday. They're not lost weight in that time. It's just too rapid. It's too acute. So in the acute leukinias, we don't see that third red flag, the weight loss. But as we see length with chronic leukinias, we do. So three red flags, unexplained fever, unexplained night sweats, unexplained weight loss. If you see those, you can go straight to the doctors. Right. Sometimes there are two B symptoms. So if you don't finish your associates, you might also hear of them being described as B symptoms as well. Right. Diagnosis of A and L. So we've recognized from the signs and symptoms that someone is falling. So we're going to run some tests. We're going to do some blood tests. We might look at their bone marrow with the bone marrow autopsy. We're going to see, for A and L acute, we're going to see more than 20% blast cells. So here's a blood smear. We've got blast cells. We can recognize blast cells because they've got big nuclei. So more than 20% blast cells when we look down the microscope. The actual white blood cell count that we get, the overall count, could be high, low, or normal. Often it is high because we've got uncontrolled proliferation. But remember, it's lots and lots of blast cells rather than mature cells. So sometimes it can be normal or even low. Neutropenia. So we also see a low neutrophil count because there's lots and lots of the blast cells, not the mature cells. David Richard talked about different types of categories of anemia. Microcytic, macrocytic, normocytic, normochromic. The type we see with leukemia is normocytic, normochromic. Why do you think we get normocytic, normochromic pneumonia? Why do we not see microcytic, hypochromic, or macrocytic pneumonia? Why is it normocytic? So normocytic means they're a normal size, normochromic means they're a normal color. They've got the normal amount of hemoglobin.

Any ideas? There's nothing wrong with the red blood cells. Exactly. It's not even crowded. Exactly that. There's nothing wrong with the red blood cells themselves. There's just not enough space to make them. So we produce fewer red blood cells. But each red blood cell is perfectly bought. Nothing wrong with them. They're not lacking iron. They're not lacking B12. They're perfect in themselves. There's just not enough space to make as many as we need. Thrombocytopenia, no platelet count. Blast cells in the peripheral black lung. And then lastly, the white blood cells are NPO positive. What does NPO stand for? What's fangal site reginal? What's fangal sites? Myeloperoxidase, the thing that makes not green. So if it's a myeloid leukemia, we will see NPO because they were ultimately going to become granular sites. They're going to become these cells that produce the greenest knot. They release their granules.

So NPO positive. Having a diagnosis? Treatment then? Treatment usually is chemotherapy. So chemotherapy is where chemotherapies are given cytotoxic drugs. Cytocell, toxic, toxic. Drugs via a pick line or a port. I'll show a picture of that in a minute. Drugs are given in different phases. So chemo is often given in two to six week cycles. And those cycles are repeated. So you might be on a cycle of, say, two weeks on, one week off, two weeks on, one week off. Or you might be on a cycle of six weeks on. It varies. So we've got combinations of chemotherapy drugs that are used to do what's called induction. Induction is about trying to get the condition, the cancer, into remission. Into remission. Our definition of remission, definition of remission, for looking at is to get the blast cell count down below five percent. Down below five percent. So chemo is initially given in cycles until the patient's blast cell count is below five percent. Following that, then we get more cycles for what's called quick consolidation. So this is post remission. The patient is in remission. But now, rather than trying to slow down the growth, we're now trying to reduce the risk of relapse. Reduce the chance of it coming back again. Sometimes patients need a stem cell transplant. So consolidation can also be used to prepare the body ready for stem cell transplant. Let's look at those pick lines on the box there. So here is a port. A port would be a device that's put just underneath the surface of the skin, often in the chest. And it has a tube from it directly into the heart. So into the right atrium there. So this means that drugs can be administered through the port. So rather than having to damage by going in, you know, if you deliver drugs into the bay intravenously, because these are nasty, nasty drugs, they will just burn. They will just burn the tissues all around there. So they want to get the drug direct into the heart so it then gets diluted as quickly as it can around the body so it has its effect at a more dilute level but everywhere. Rather than burn where it goes in. So you've got a port is one option. The other option is the PICC line. So PICC line stands for, I'm sure I wrote it down, Peripherally Inserted Central Capital. So PICC line is a tube that goes in through a vein in the arm, usually the arm, fed up inside one of the veins, again direct into the right atrium of the heart. So again, the drug can be administered straight into the heart without causing damage to the vessels where it's going in. The advantage of the PICC line is that blood samples can also be removed, often from the same site as well. So kids or adults being treated on a regular basis, it just means they're having less invasive techniques done. Once these have been put in place, they can have each round of treatment without having to have more saps, more needle stick. Side effects for chemo?

What have we got for side effects of chemo? Killing healthy cells too. Killing healthy cells.

Which healthy cells does it target? Red cells, absolutely. It's targeting cells that are dividing rapidly. This is what chemo is trying to do, kill any cells that are dividing rapidly. So that would be the cancer cells. But there are healthy cells in the body that also divide rapidly. Which cells in the body that are healthy cells divide rapidly then? So we have red cells, hair follicles, absolutely, so side effect might be hair loss. Red cells, so side effect might be anemia.

What else is dividing rapidly? Skin, absolutely, yes.

So we might get things like particularly the mucous membranes. The cells there divide very rapidly. So we get mouth ulcers. The lining of the gut becomes inflamed.

So we get nausea, we get vomiting, we get diarrhea. Any others? What about the boys? What cells have boys got that are rapidly dividing all the time? You're all thinking it. Sperm cells, yes.

So males having chemotherapy or side effect might be male infertility. So we've got those rapidly dividing cells in the testes become affected and then male infertility. Now I've missed any from my list. Sometimes patients give them a stem cell transplant. So for this, the donor can donate stem cells, healthy stem cells, two ways. One way is from taking a sample from the pelvis. But that's only done one in ten big day. Nine out of ten donations are made by this lady here. You sit on a machine that takes the blood out of one arm, filters out the stem cells and puts it back in the other arm. So it takes you an afternoon or a day of sitting on a machine to donate the stem cells and save someone's life. Meanwhile, the poor patient, before they can receive the donated cells, we have to kill off all of their bone marrow. So they are given strong chemo, extra strong chemo to try and kill off everything. Once their bone marrow has been cleared out completely, it's a simple intravenous to receive the new stem cells. The stem cells will come in intravenously. They will migrate to the bone marrow and set up their home and hopefully repopulate the bone marrow, healthy cells. Cancer has gone.

That's the hope. Prognosis for AML then, chemo needs to complete remission in 80 to 90% of younger patients but only 45% curate. Older patients tolerate chemo less well. Cure is fighting the survival of 15%. So before we take a break, I just want to cover some key terminology here. There's term remission versus the term cure. So remission, by definition, particularly for our acute leukemia, is the blood cell to have needs to go down to less than 5%. So we've not got rid of all the blood cells completely. The amount of blood cells is higher than it would be often in a normal healthy person, but it's not so high that it's causing problems. Now we can measure that quite easily.

We can measure the blood cell power quite easily. Cure is a very hard thing to measure. The only time we can say someone is cured of a condition like cancer is when they've died of something else. So we can't say they've been cured until they've died, hopefully of an old age, from something that's not that cancer. So it's a very hard thing to say cure it. Instead, what we use is survival rates. So we use the term 5 years survival, 10 years survival, or maybe 1 years survival. So what was the case here?

We had an older patient's survival rate, 5 years survival rate was 15%. That means that 15% of patients will be alive 5 years later. Survival does not mean well. Survival can mean very, very poorly.

You're just not dead. Or you could be alive and well and happy and going off to holidays and travelling with one another to do normal things. So survival rates are a very vague sense that we don't know does it mean they're alive and well or they're alive and very poorly. But it is a measure we can use.

Are people still alive or not? Okay, bone marrow transplant, you can donate bone marrow via the antinatal bone marrow trust that you spit in a tube. They use that to work out your haplotype. Remember we took the haplotypes for HLA yesterday, day before, day before that, Tuesday. To work out what markers you've got on your cells that say who you are. They type you, they then put you in a filing cabinet. And they reckon that you've got a 1 in 800 chance of being called up. So I've been on the bone marrow register for about 15 years. I've never been called up. I've noticed a couple of people who have, but it isn't that likely. So do something that can save people's lives. Get yourself on the register if you feel happy to. You can go to the website. They will send you the swarming kits in the post. We might see if we can get them over for one of our practicals that you can do it at the end of the practical. Otherwise, get yourself registered and save your life. Right, 10 minute break then. And then we have got 3 types of leukemia, 2 types of lymphoma, a mile over to get through in the last hour. Okay, have a break. So I have been bringing around another case study for you. We're not going to do it today. We will go through the answers. Our next case study session isn't until about week 8. We've got a long, long gap before we do another case study session. So this is just one because it links to today's material. You can look at the gap between now and our next case study session. We'll get into the next one. We'll go through the answers at that point then. But it links to today's material. Right, let's crack on then. We have got a lot to get through, have we? I won't be spending any more years long going through the underlying keynotes because I want you to go through the first one in lots of detail so that it makes sense. If you understand the principles, it's much easier to learn and remember. So let's rapidly go through. A-L-L, this is our acute, so lots of lots of blast cells, immature cells. Lymphoblastic, so it's lymphoid leukemia, uncontrolled lymph pressure of the Y-cell. This is the one that affects children. So peak age, for people to get this, is between naught and four years of age. So it's our little kids, unfortunately, getting this leukemia. It accounts for 80% of children with keynotes, affects 1.1 per hundred thousand. It's mostly B-cell. So we know it's an lymphoid leukemia, but of course it could be T-cell or B-cell. It's mostly 85% of patients are B-cell best. Just like the minority one, where we had n news, and seven, this one is scaled or rated L1 to L3. Different treatment protocols in terms of what chemo, what dose, how long before, depending on which category a person was. Silent symptoms, acute, just like our A-cells. So it starts rapidly, but it's acute because it's got brain cells. Bone pain, it's happening in the bone marrow, so children have bone pain. Bone pain is not a common thing, children should not have bone pain. Symptoms of bone marrow failure, anemia, infections, bleeding. Generalized lymphadenopathy, isn't it?

Generalized lymphadenopathy. Lymphadenopathy is our swollen lymph nodes.

Generalized means all over. Why do we see enlarged lymph nodes all over the body for these kids? Where is the leukemia happening?

Where does it happen? Lymphocytes. So it's the lymphocytes which are made in the bone marrow. Where do they then go? Lymph nodes. Lymph nodes. So the abnormality happens in the bone, in the bone marrow, and then those abnormal cells can get spread all over to all the lymph nodes around the body. So we'll see that it is different to our lymphomas. The lymphomas are our cancers of the lymphoid tissue. A cancer that starts in a lymph node. So that will be in a simple site. Acute lymphoblastic leukemia, it starts in the bone marrow and could go over to all the lymph nodes because that's where these cells go. Hepatasplenomegalin, enlarged spleen, enlarged liver. What are our sites? Are there any extra lymphoblastic pieces? Spleen and liver. So when the bone marrow fails, we can switch back on our embryonic, our fetal blood cell production. And that happens in the liver and the spleen. So the liver and the spleen become enlarged. Infiltration sites are sites where the cancer can spread to. And where these are at all, it tends to be central nervous system and the testes. Nobody quite knows why, but these are the places that it goes to. So sometimes if it goes to the central nervous system, so the abnormal cells migrate into the central nervous system, it can result in headaches. Headache is a red flag in children. Grown-ups get headaches all the time. We tend to get dehydrated. We tend to get tired. We get eye strain from computers. Children should not get headaches. They tend to self-regulate hydration, but better than us. They don't tend to get eye strain. But some children will have simple eye strain. Some kids will be spending too much time on screens and get headaches. That does not mean they have a finger. But if it's an unexplained headache, that's definitely caused to go for further investigations. So a little girl that I know, her first and main sign was headache. She had headache. Mum took her to the doctor's. Doctor, very, very good doctor, thought this is not right in a five-year-old. Asked for some blood tests to be done. She was in hospital by the next day and started treatment for leukemia. So what Mum thought was a headache, 24 hours later they're now in their worst scenario ever and looking at a horrible, horrible next few years. Headache in children is not right. Sanctuary sites are places where abnormal cells can hide from chemotherapy. Chemotherapy doesn't get into every tissue to try and heal the cells. It struggles to get into the nervous system. It struggles to get into perhaps the testes, which is why perhaps these are the reasons why these are sites where it's found at later stages. So to try and prevent this, when we look at the treatment, the kids who are treated for ALL will have standard chemo and then they have further chemo to try and target those sanctuary sites. Extra chemo to try and get it where it's hiding. Diagnosis, blood tests again, biomorrhoboxies. So it's acute leukemia, so one of the things for more than 20% of the last cells. Leukocytosis can be higher than 200 times 10 to the 9th. If you look at the case study in front of you, a normal white blood cell count is between 4 and 11 times 10 to the 9th. So higher than 200 is a lot of white blood cells. The anemia yet again, normocytic neurochromic, neutropenia from the cytopenia. This time the white cells are NPO negative. Myoproxidase is stored in the granules of granulocytes. This is not a granulocyte cancer. This is a lymphoid cancer, so NPO negative. Treatment, the first type of treatment, since we're a little girl, I know the first treatment she was given is put on steroids straight away within 24 hours. She was receiving steroids, steroids dampen down the immune system. It will suppress the production of white blood cells, and that's just a temporary step whilst the doctors are planning what the hell we're going to do. So this is a temporary thing, calm down the immune system whilst we come up with a treatment plan. Chemotherapy, psychotoxic drugs by pick lines or ports again, for example Vincristine. Induction is used to try and get the patient into remission. It might be more than one cycle.

Induction is not one cycle. It's multiple cycles until that last cell count comes down. The question, the difficulty, is these are little kids. How much chemo can a four-year-old's body cope with? And unfortunately, the answer is not always enough. So they end up very poorly.

Sometimes they sail through, but sometimes they end up in intensive care because it causes not fun problems. So induction, after induction, so once they're in remission, then we go for consolidation. This is where they're trying to target those infiltrates, trying to get the cancer where it hides in the sanctuary site. So trying to prevent it spreading to the central nervous system. Following that, these kids then have another two years of further chemo to try and stop it coming back. So a typical treatment cycle for kids to lay out is about three years, and that's if it goes well. This isn't something that you cure and get rid of in six weeks. They're looking at three years of horribleness. Newer therapies around the chemo.

We've got immunotherapy. So some of you have heard of CAR T therapy. This is where you take the patient's T cells and you train them. You genetically engineer them so that they recognize the cancer cells. And then you kill off all the bone marrow again, put in the CAR T cells, and hopefully their own immune system starts to kill the cancer. Trials are ongoing.

Stem cell transplant. For ALL, most kids actually do quite well with the chemo. The three years of chemo does tend to work for most kids. Not all of them will need stem cell transplant.

Some will. Some will need more than one stem cell transplant. The first one might not work. Prognosis, good news story this one, 90% of kids are curable. It goes away forever. So standard Keynote, three years worth, it's a nasty day, but that can get rid of it for 90% of kids. Trials ongoing for new therapies for those who pass it isn't so successful with, it seems resistant. When adults get ALL, cure is less common, and more often a stem cell transplant will be used in adults than is needed in children. Okay, so that's our ALL. C and L, chronic myeloid linking. So we've got uncatrolled proliferation resulting in lots of mature myeloid cells. The mutation might still be in one of the stem cells, one of the immature cells, but the result is lots of mature ones. Peak onset, so we're back to the L today, 65 to 85 males, more than females, 1.3 to 100,000. This one is linked to a genetic effect known as the Philadelphia chromosome. So 90% of cases have this Philadelphia chromosome. In the Philadelphia chromosome what we get is his chromosome 9, and at the bottom of chromosome 9 we have this gene called the ABLE gene. It's a tyrosine kinase gene. On chromosome 22 we have BCR, which is our breakpoint cluster gene. I'm pretty sure that's what it is, not my gesture. Breakpoint cluster region on chromosome 22. With the Philadelphia chromosome you get a crossing over and a swapping. So they swap the ends of their chromosomes. So on chromosome 9 we've now got part of that breakpoint cluster. On chromosome 22 we've got the ABLE gene here. So we've got the breakpoint cluster primer and promoter region and the gene for the tyrosine kinase. So this creates a fusion protein. A fusion protein for a kinase with high activity, and that promotes growth. So with the new fusion protein we get more cell growth, more cell division, cancer. So it's our Philadelphia chromosome. Signs of symptoms for CML, remember it's a chronic one, so it tends to be a slower, progressing, gradual onset of symptoms. We can divide it into phases. The initial phase, known as the chronic phase, can be asymptomatic. Patients have no symptoms that they're aware of at all, but they go for a random blood test to check for something else, and it comes back with it looks like they might have CML. So 90% of cases are diagnosed in that asymptomatic phase from a blood test but was not needed for these symptoms. They were having something else done. They had an extra level or something like that because they're getting older and it's just picked up on the stem. So in that we get an accelerated phase. In Swiss films we start to see an increase in the number of blast cells. We start to see symptoms. We're in fear of symptomatic stage. Fatigue, weight loss, night sweat, red flags. Well, fatigue isn't a red flag. Most of us have not been. Weight loss, night sweat, fever, red flag, red flag, red flag. Weight loss, we see, because of the chronic, there's been going on for years. So the weight loss gradually comes off and off. It's unexplained weight loss. So weight loss when the person is not dieting, not trying to exercise. Splenomegaly, patomegaly, and I'll just leave the liver. That caused like a space around stomach. So they start to feel full. They have a meal. They don't need to eat as much as they want to feel full. That might also contribute to the weight loss. Gout. Gout is their position of uric acid, often in the toes. Very, very painful in the toes. The reason they get gout is because uric acid or urate is produced when we break down DNA. So if you break down purines, that's part DNA, we produce uric acid. And of course, we're breaking down DNA because we're proliferating cells, divided by lots of cell turnover. So we end up more gout, but with more uric acid and gout. Bruising from the cytoplena, leukostasis. Look how many white cells are in this blood sample here. On the left, a normal blood sample, plasma, here's the buffy coat, a tiny layer, red cells. Here's our CML patient, red cells. Look at the buffy coat. It's enormous. So that shows just how many excess white blood cells they're making. A huge number. And this causes leukostasis, clumping of the white cells seen in circulation. Following on from the accelerated phase, we get acute phase. So the number of last cells goes up even higher, and this is where the cancer changes from a chronic leukemia to an acute leukemia, as it's progressing. Diagnosis. So high white cell counts, usually more than 15 times 10 to the 9, but it can be over 500 times 10 to the 9. All of the different myeloid cells. You might see high neutrophils, eutrophils, phasophils, monocytes. You might see them all high. Increase in basophils. Normally they're very rare, aren't they? They're rare cells in the circulation. Normocytic, normochromic anemia because there's a lack of space in the bone marrow. Platelet counts as a weird one. Because platelets are a myeloid cell, their count might actually go up. We might get thrombocytosis, high platelet count. But often, even often, it can be reduced because of lack of space, thrombocytope. Or it could be a bit of both, so a higher production but not enough space, and you end up with a normal amount of platelets. So it can be a bit confusing. We can also look at various markers in the blood, some things like alkaline phosphatase. It's produced, let me check my notes. Alkphos, so it's reduced in chronic myeloid leukemias but increased in myelodysplastic syndromes. It's an enzyme found in the granules or granular sites. So alkphos found in the granules, for some reason though, although you've got more granular sites, the amount is reduced in CML. Weird contradiction, higher as well. LTH and neurorates and LTH lactate dehydrogenase found in all cells in the body. It's increased in gut cancers. Uruates, we've already talked about, it comes with a gout. So it's produced by breakdown of DNA. And then FISH is what we can use to diagnose. This is FISH, fluorescence in situ hybridization. Let me drag that out the way. So we can fluorescently label chromosome 22 in one color. So these are all chromosomes. Chromosome 22 in one color, chromosome 9 in another color. And here we've got a bit of both. So that's our Philadelphia chromosome, where we've got the fusion together. So it can be used for diagnostics. Treatment. The first line of treatment for chronic myeloid leukemia is not chemo, which is nice. Chemo sucks. It's a targeted cancer drug. Targeted cancer drugs are drugs that try and block cancer. They try and run. They try to kill cancer cells. They just try and block their action. So we've got a tyrosine kinase inhibitor. Remember our fusion product was that BCR-ABL? So this is an enzyme that normally converts one thing to another and cells divide. But we've got a drug here that we can use to bind to that enzyme, blocking its action. It's just an enzyme inhibitor. So it's not killing cells as such, but it blocks the kinase activity. So the tumor cells can no longer proliferate. If needed, those cell transplants can be used to try and cure the conditions that they come with a risk of mortality, so risk of death. Prognosis, this drug, the tyrosine kinase inhibitor in Mitana, has improved and finally survived from 33% to over 90%. What an amazing drug is that. So, you know, whereas CML used to be, you know, not correct. If you've got that, the odds weren't wonderful. But now you can take these drugs, which are not as nasty as chemo, and not with an outside effect, but they're not as nasty as chemo, and lots of people live near normal life expectancy, which is fantastic. It often goes through this asymptomatic phase to start with, gradually getting worse before it goes to then your fatal acute phase. Stem to our chance that we've already talked about. Right, chronic lymphoid leukemia, and then we'll take a 30-second break. CML, leukemia, uncontrolled proliferation of the white cells, lymphoid, chronic, so we get lots of mature lymphocytes, lots of the mature ones. This is a disease of the elderly, so typically affecting people over 50, T-cage over 90. It's the older folk that get this one. Men, more than women, 6.3 to 100,000, so possibly the most common of them all. Almost all are B cells rather than T cells, and a huge overlap with the lymphomas, as we'll see. We'll look at the lymphomas later. Again, often asymptomatic to begin with. Many patients and I know from blood tests for other things. They're feeling a bit run down, a bit tired, and the doctor as well, a bit alone, but they're probably on the tea and toast diet. They're probably anemic. We'll send them for blood cancer. Oh, look, they've got a higher count than they should have a lymphocyte. It might well be C-L-L. Many patients survive long periods with almost low symptoms. Elderly patients, very my most people are diagnosed with this in their 70s, 80s, 90s. Most of them will die of something else. It is not a list that kills them. They die with the leukemia, not from the leukemia. We've got lots and lots of mature lymphocytes. The abnormality has happened in the bone, but it's migrated to the lymph nodes. So we've got symmetrical, just like with our A-L-L. It can go to all the lymph nodes, so it's symmetrical. It's painless, so we get an enlarged lymph node, but you can poke it, and it doesn't hurt, unlike the infection where our glands are sore. Lots, not lots, may. They may have symptoms of anemia. They might not. They may get bacterial infections. They may get viral or fungal infections, because it's one of the chronic ones, and we've got division, division, division, division. They are burning through the energy, but slowly, so weight loss is a gradual thing. Over the years, they lose more and more weight. Diagnosis, we've got lymphocytosis, so a high lymphocyte count, over 5 times 10 to the 9 of just the lymphocytes. Possibly, though, up to 300 times 10 to the 9 of lymphocytes. Most of the white blood cells appear as small, round lymphocytes. So here is lymphocytes, so a small, round cell with a big nucleus. These other cells in between them, so these are known as smear cells. The leukemic cells are quite fragile, so when you put a cover slip over the top of the blood smear, they pop, and we end up with these smear cells that you can see in the picture. When we looked yesterday at less than Tuesday at our introduction to the Thud and Lean system, do you remember there were different markers on the different types of lymphocytes? So the markers were B cells with CD19. So when we immunotype these cancer cells, these abnormal, lots of them, white blood cells, they have CD19 on the surface, which tells us they're B cells. Normocytic, normal chromokinemia, but it's happening in the bone marrow, thrombocytopenia because it's overcrowded, and the bone marrow. Treatment. Remember that this often has very few symptoms and they can live for a long time with this one. So often there is no treatment needed. The approach is what's called watch and wait. Monitor, check it's not going to work so time, but just watch and wait. No treatment is needed. If you give someone who is 85 a load of chemo, you're going to do more harm than good. Just like the little kids, if their bodies will struggle to tolerate it. You could give them steroids, like we did in the little kids, dampen their immune system, so reduce the amount of white cells they produce. We could give them targeted cancer drugs, just like if that's a myth. We've got another one here, abruptionid. So again, it's blocking their tyrosine kinase. It's a different kinase. And so we look at the same principles. The immunotherapy, training the immune system to target the cancer cells. That's developing new sort of therapy. Chemo, very rarely used for CELA. You know, you're not likely to be giving someone in their 80s or 90s chemo. You will just make them sick and miserable and not able to enjoy their later years. Sten cell transplant, again, not usually appropriate in the elderly. They just can't tolerate what it takes. Prognosis, about 70% five years survival rate. Now, if you get diagnosed at 88, if you're alive five years later, you've done a little bit better anyway, regardless of what's got you in the end. So 70% survival is pretty remarkable, given the age of the patients we deal with. Most patients will die of something other than misleukemia. They have it, they die with it, not because of it. 30 second decompression, and then we'll go on to the lymphomas. Okay, catch your breath. That was a lot to take in on the other leukemias. Okay, so leukemia was all about cancer of the white blood cells, taking place in the bone marrow that those abnormal cells could be migrating elsewhere. The lymphomas, on the other hand, is cancer of the lymphoid tissue. So the cancer is not originating in the bone marrow. The cancer is originating in the lymphoid tissue. The lymph nodes, the tonsils, the adenoids, the spleen, the thymus. So the picture here shows an enlarged lymph node in the neck. So you can see just how big they can become. So it results in the lymph node that is full. It becomes swollen, it becomes enlarged because it's full of abnormal T cells or B cells. Lymphadenopathy, enlarged lymph node, tends to be non-tender rather than painful. It looks like it should be painful, but it tends to be non-tender. And we can divide the lymphomas into Hodgkin's and non-Hodgkin's lymphoma. So Hodgkin's accounts for 40% of cases, non-Hodgkin's 16%. The key difference is that in Hodgkin's, the lymphoma cells, the abnormal cells are known as Reed Sternberg cells, Reed Sternberg cells. Whereas in non-Hodgkin's, we don't see these Reed Sternberg cells. Okay, so we only see the Reed Sternberg cells in Hodgkin's lymphoma. If someone came in with an enlarged lymph node like that, you wouldn't be taking a biopsy. So you'd need to take a sample and then stain the cells for lymphocytes to see if it's full of level lymphocytes. Is there any signs of any infection or does it look to be full of abnormal cells? Hodgkin's then. So this is abnormal B cells accumulating in a lymph node, but the abnormal cells, these ones known as the Reed Sternberg cells, they only make up a small amount of the tumor. So they are what makes it Hodgkin's, the Reed Sternberg, but they are only a small bit of it. Most of that lump is actually from other cells, inflammatory cells. So we've got lots of inflammation, lots of inflammatory cells amongst those Reed Sternberg tumor cells. Hodgkin's is one you might have heard of before because of your friendship groups. The age range that it affects, it has two peak age ranges. So one of them is from 15 to 35. In other words, your age. So this is one of the cancers, unlike the ones which affect the midterms or the elderly. This is one of the ones that affects the young adults. Males more than females. In my experience teaching classes, it's usually one or two of the boys in the class or someone has got a sibling, my brother brought home to come and tell me, had Hodgkin's is well now. The other age that this affects could be over 50s, together with young and older, 3.3 to 100,000, boys more at risk than girls. Sign of the symptoms. Asymmetrical, painless, lymphadenopathy. So in the leukemias, we saw generalized lymphadenopathy or symmetrical lymphadenopathy because it started in the bone marrow and spread to the lymph nodes. Here, it's asymmetrical, one sided because it started in that site. It's not started in the bone marrow and gone there. The problem happened in that lymphoid tissue. Usually, it starts in the neck and then it spreads by the lymphatic chain to other lymph nodes. So we can look at the different stages here. Stage one of Hodgkin's is where you have one affected lymph node. Stage two would be when you have two affected lymph nodes. So it's spread from its original site to a second lymph node. Stage three is when it's spread and crossed the diaphragm. So it might have started up in the neck, but now it's spread to lymphoid tissue below the diaphragm. It's a spleen. It may be a lymph node in the groin. Stage four is where it spreads non-lymphoid tissue, so perhaps the liver. So it's spread beyond the lymphoid tissue. Splendid ligament. Spleen is a site that it often spreads to, so we enlarge spleen, causing symptoms of fullness, not wanting to eat all your dinner. Fever, night sweats, weight loss. Red flags. So people your age. Fever, night sweats, weight loss. Unexplained fever. Unexplained night sweats. Unexplained weight loss. You go to the doctors. Puritus. Puritus is itching. And one of my students in the past said, her brother, when he went into remission, the key thing the consultant said to him is if you ever get any unexplained itching, you are to phone me and book straight in. So Puritus is because we've got all those inflammatory cells. Remember the REIT sperm cells was the tumour of it with lots of inflammatory cells around it, releasing inflammatory mediators that cause unexplained itching. So unexplained itching, this family has told you come straight back, straight back to see us. Continue to know you're seeing a minority of doctors, not seeing them all the time. We've looked at the stages already. Diagnosis, you need to do a full blood count because you want to exclude things like leukemia. You know, other causes of an enlargement. No could be a leukemia, less likely if it's a unilateral rather than generalized. If the blood tests, they didn't blood test normocytic, norochromic anemia, if they've got anemia at all. Remember it might not be affecting their bone marrow until stage four. Starts here, spreads, spreads, might then go to the bone marrow. So anemia tends to be a later symptom or sign. If an othea, neutrophilia, again, sometimes later, platelet count can be affects. Advanced disease, lymphopenia, thrombocytopenia. Mostly, diagnosis is going to be for the biopsy. Taking a sample from that lymph node, and our marker for the re-stir motels is CD15. Remember CD19 was our marker for B cells. CD15 is our marker for re-stir motels. So if we can label the cells against CD15, then we know that there reads Dernberg cells. Pet scans, they've been useful for identifying whether the tumor has stayed in one place or spread to other lymph nodes. So it's more often used for staging initially, and then for monitoring how it's doing treatment. Has it shrunk the tumors? Has it spread further or is it not spreading now? So pet scans are usually more for the staging. Treatment, steroids, let's reduce all those white blood cells so we can reduce the production of white blood cells. Chemo, two to six cycles of chemo. ABBD is a combination of chemo drugs. So ABBD all stand for different drugs. Then radiotherapy. Now radiotherapy could be a single dose of radiotherapy or it could be every day for six weeks. So radiotherapy means shining high-energy waves of energy at the tumor to try and kill it off. To make sure we hit the right bit of the tumor, people need to lie incredibly still whilst they're having these energy waves shot at them. So they often have these cages to hold them still. So they have to lie incredibly still. If you're trying to target a tumor specifically in the anoids and you don't want to target your brain, you need to stay still. Immunotherapy, targeted chemo drugs, stem cell therapy. Good prognosis from Hodgkin's. 80 to 90 percent, 10 years of viral rate. So 8 or 9 out of 10 people with Hodgkin's will still be alive 10 years later and often need good help. So even good prognosis. But it does depend upon the stage it's diagnosed at so if it's picked up early, better prognosis. If it's picked up later, not such a good prognosis. Chemo can lead to high cure rate even in advanced disease though. Most things, if you leave it too late, not good. But with Hodgkin's, not too bad. Downside to Hodgkin's is that all the treatment often leads you at increased risk of having another cancer, a different type of cancer, a secondary one and a side effect of all the chemo. So it sucks. You might survive Hodgkin's and then later in life you get another round of totally different cancer and it's not fair. It isn't fair. Nothing about cancer is fair. It sucks. Did you have a question? In the last few or the next months of stages, when it starts spreading, does those ligands get swollen as well? No. And it just seems so. So they may or may not. So it's spread to different lymph nodes. Stage one it's in one lymph node. Stage two abnormal cells have been detected, possibly through PET scans. So PET scans detect things like glucose use around the body. So if it can detect there's another lymph node over here that is using more energy than it should do, it might not yet be enlarged. But you're thinking, okay, let's do a biopsy of it then. Why is it using more energy? Stage two to all lymph nodes. Stage three crosses the diaphragm. Stage four runs a non-lymphoid tissue, either liver or maybe bone marrow. Bone marrow is an lymphoid tissue. I know it's a prime one, but yeah. Non-Hodgkins often be cell-based, more variable presentation. So the patients have wider different types of symptoms than you do with hodgkins. You can see the lymphoma here in large lymph node under the armpit. So this is an axillary lymph node, swollen up, 11th most common cancer, 21.5 for 100,000. That's the highest of all the ones we've seen today. So this is probably the highest of the blood cancers. Typically even below 45, more often than not elderly, so 70 to 85 yards. Asymmetric, painless lymphadenopathy. The abnormality has happened into that lymph node. It's not the bone marrow spreader. It's happened at that site. Less fever, less night sweats, less weight loss. Can you see the hodgkins? But you do sometimes see sore throats. All of them are new. So remember the lymphoid tissue includes the tonsils and the adenoids. So it's just them and getting involved. Antosymptom, so digestive problems due to spleen and liver enlargement. Itchiness, throatus, anemia, thrombocytopenia, neutropenia. Normocytic, noremic anemia, neutropenia, thrombocytopenia, lymphobiopsy, which show no reeds starting to burn, that's going to not push it. It does not push it. There are some other chromosome abnormalities that are quite relatively commonly seen in NHL. So they might look for those specific chromosome abnormalities. They might not. Lots of scans, lots ofoscopies, so endoscopies, coke, and anoscopies. All of those different oscopies to look at different parts of the body. Pet scans can be as a mistake. Treatment, similar again, steroids, chemo, immunotherapy, radiotherapy. Here's another one of these frames to hold people still whilst they're receiving the radiotherapy. Sometimes, you can't see it under the little picture yet, tattoos. People have a little tattoo done to show where the radiotherapy should be targeted to make sure they get the same spot. If you've got to have it every day for six weeks, you want to get the right spot every time. The champion has a little tattoo to target it. Oh, that's because I need to touch the screen. Fifty-five percent survive, your rectum is to vibrate. Often start slowly, so in don't it, being swaffled, slowly progressing, but then it goes aggressive towards the end. Last one to cover in the last five minutes, then multiple myeloma. Leukemia, cancer of the white blood cells. The lymphoma, cancer of the lymphoid tissue. Myeloma, cancer of the plasma of B cells, the antibody factories. So because these cells are producing antibodies, they are antibody-strating B cells, and they produce a copy of something called a paraprotin. So it's an immunoglobulin. It's not a functional antibody. It's not useful in any way. It's just lots and lots of copies of this immunoglobulin. So much so that it can be detected both in the blood and it even comes out in the urine because there's so much of it. So this is called a paraprotin. Multiple myeloma, rare before 40. Again, another condition of the epithelic, 70 to 89-year-olds. 9.9, 100,000, more common in males and more common in African and American. Bone pain. This one is happening in the bone marrow. So the abnormality is happening in the bone marrow. These plasma cells, lots and lots of them. So we get breakdown of bone, and we can see that in this picture. Here's a picture of a skull. Can you see the patch of less bone material here in the skull? That's where the bone has been broken down. This is the forearm. You can see a darker patch here, less bone material. Here it is in a different orientation. So we're getting breakdown of bone. So bone pain, the bone gets weakened. So often a fracture might be one of the original problems. Little old Doris comes into A&E. She's broken her arm. They do some tests, and it's not just simple osteoporosis or that she broke her arm. There's something going on that's not good. Anemia, thrombocytopenia and leukemia. Because we're breaking down bone, we get hypercalcemia. That calcium from the bone material is being released into the bloodstream, and that causes symptoms like thirst and nausea, fatigue, things like that. The hypercalcemia also damage the kidneys. It's supposed to be a kidney failure. And we get an aniloidosis, which is deposition of abnormal proteins around the body, possibly on the kidneys, possibly in the heart. So again, a knock-on of problems. Diagnosis, overpowering of bone marrow rates. We've got more than 20% plasma cells. Paraprotein is the main one. You can detect it in the blood. If it's in the urine, it's known as a Benzed-Joan protein. So urine tests. So you can diagnose this one from a urine test. Simple weed test. Then they can look for the presence of Benzed-Joan protein. So paraprotein is small enough to get through the kidney filter and into the urine. Because it's overpowering of bone marrow, we get pancytopenia, so low calcium, everything. X-rays, PET scans, can be used. Fish. So that for essence, in-situ hydrodynamics. A whole lot of tests could be done. Treatment, watch and wait. So again, if it's someone really elderly, do you really want to give a nasty, nasty, nasty drugs? Let's just see what happens. You might opt to give steroids, a relatively gentle treatment. You could go for targeted cancer drugs. And this is weird. It's drugs like thalidomide. You might have heard of thalidomide as a drug that was prescribed in the 15th and 16th for mothers to reduce morning sickness. But the consequences, the side effects, were problems with the children. The fetuses were affected by the drug. There were lots of physical deformities. But no longer used in pregnancy, but now used in other conditions very well. Doing useful things. Slowing down cancer cells. Key bones. Those are transplants. But most often, and the most important thing with these, is pain control. Managing little of Doris' pain levels. Her quality of life. So keeping her comfortable. This phosphates, reduced bone damage, radiotherapy surgery might be needed if there's problems, the bones crumbling, collapsing. 29% survival, 10% survival. Good palliative care is super important. Curates are not great for this one. So it's about keeping people comfortable. That covers everything we have done.