Transcription
It's Meta Kosis. Welcome to my channel. It's a playlist on hematology and oncology. In the previous video, we had the introduction, and we knew the difference between acute leukemia and chronic leukemia, Hodgkin's lymphoma, and non-Hodgkin's lymphoma.
In today's video, we'll discuss acute leukemias in greater detail. As you know, acute leukemias include acute lymphoblastic leukemia and acute myelogenous leukemia. Leukemia means bone marrow problem; -emia means blood; white blood cells. It's a white blood cell malignancy originating from the bone marrow and going to the blood. Since this is an acute leukemia, the patient will be much younger, and the cells will be less mature. So we have blasts such as myeloid blasts; we have here mono blasts, myeloblast, lymphoblast.
Remember our discussion on hematopoiesis? We start with multipotent stem cells; we have myeloid lineage and lymphoid lineage. Okay, so acute myelogenous leukemia is here. Okay, it's malignancy of the parents that produce these cells. Acute lymphoblastic leukemia, on the other hand, is here; that's why we have lymphoblasts, the parents of the lymphocytes. So AML is here, and ALL is here. One thing to remember: acute myelogenous leukemia have these azurophilic granules known as Auer rods. These are peroxidase-positive. Pretty cool. How to remember that? The Auer rods are myeloperoxidase-positive. If you remember our discussion on white blood cells, I've told you that when we have a test tube of centrifuged blood, we have red blood cells in the bottom, we have plasma in the top because of the different densities, and in the middle we have this little tiny area called the Buffy coat where we have the white blood cells and platelets. And I've told you this white area sometimes can appear greenish, and I've told you why: because neutrophils produce myeloperoxidase. And here the Auer rods are myeloperoxidase-positive. Kind of makes sense. Again, leukemia: acute or chronic; acute: ALL or AML; chronic: CML or CLL.
The risk factors of developing acute leukemia: it's both genetic and environmental; the good old philosophical argument: nature versus nurture. Antineoplastic agents, ionizing radiation. What's the difference between ionizing and non-ionizing radiation? If you remember your physics, here is the electromagnetic spectrum with the visible light in the middle. The frequency increases as we go here; frequency decreases as we go here. As the frequency increases, the energy increases. Stuff here in the ionizing radiation include ultraviolet light, x-rays, and gamma rays. These are ionizing radiation. When we're talking about cancer, ionizing radiation is more dangerous than the non-ionizing radiation. I'm not saying that these are completely safe; I'm just saying these are more dangerous. What else we have? Hodgkin's lymphoma, we have benzene, and we have multiple myeloma.
Cool. Acute leukemias: monoclonal, of course. Any cancer is a monoclonal disorder of the early hematopoietic stem cells. Early means the cells are large; they are immature cells called blasts. Of course, as you know, immature cells are larger than mature cells because as we go down through the process of hematopoiesis, cells mature and they decrease in size. Early myeloid cells in cases of AML or early lymphoid such as ALL lose their ability to differentiate while retaining their ability to replicate. This is a great sentence. These blasts, okay, lose their ability to differentiate, so now they cannot go into sides; they cannot mature; they will stay immature for the rest of their life. Not only that, they still retain their ability to replicate. We have crazy, useless, immature cancer cells that will never mature but will keep producing cancerous cells. Horrible stuff.
These blasts, whether myeloid or lymphoid, will do three things: they will replace most of the bone marrow, crowding out normal hematopoiesis. You'll end up with pancytopenia, leading to fatigue, infections, bleeding, which is mucosal bleeding because this is a platelet problem, not a coagulation factor problem. If it's a coagulation factor, the bleeding will be deep, such as hemarthrosis. They enter the peripheral blood; increased blast numbers in the blood will lead to something called leukostasis, blood stasis due to increased leukocytes, which are these ugly, immature, large blasts. These blasts metastasize throughout the body, going to your liver and spleen causing hepatosplenomegaly, going to your lymph nodes causing lymphadenopathy, going to your nice testicles causing testicular enlargement, of course, can lead to infertility. They can lead to headache if they go to the brain. Okay, since blood starts in the bone marrow and we have a lot of blasts in the bone marrow and the bone marrow is crowded, you can have bone pain. Okay, a very good sign of leukemia is tenderness over the sternum. Okay, in those old days when we didn't have all of this bone marrow biopsy and immunohistochemistry and flow cytometry and this crazy stuff, we used to diagnose leukemia just by pressing on the patient's sternum. If it's tender, there's a very good chance that they have leukemia.
Cool. Clinical features of acute leukemia, whether AML or ALL: the onset is abrupt; that's why they are acute again, and the patient is younger. You have pancytopenia; you have generalized painless lymphadenopathy. Now, why is that? These cells leave the bone marrow and go to the bloodstream, and also they go to the lymphatic system and they go to the lymph node. The lymph nodes enlarge, but when the lymph nodes have cancer, usually it's painless. On the other hand, when these lymph nodes have infection, it's usually painful lymphadenopathy. So infection: painful. Now these cells, these blasts, will go to the skin, especially the T cells; they go to your testicles, especially in ALL; they cause headache, especially in ALL; and of course, bone pain, and don't forget hepatosplenomegaly.
No, it's leukemia; we need two things: we need peripheral blood and we need a bone marrow biopsy. Yes, we will use immunohistochemistry and flow cytometry and other stuff, but we use them over the biopsy. Okay, special staining and immunohistochemistry over the biopsy. Cool. The peripheral blood will tell you these are blasts; these are large, immature cells. You'll have anemia; it will be normocytic; it can be macrocytic; as in folate deficiency. Now, why is that? Leukemia is cancer; there is high cell turnover; we are quickly dividing cells; cell division, cell division, cell division; and we are consuming folate and more folate and more folate; we end up with folate deficiency, leading to a macrocytic anemia, as we have discussed before. Platelet count will be low; thrombocytopenia. Normal platelet count is between 150 to 400 thousand; less than 100 thousand, of course, this is thrombocytopenia. White blood cell count can be less than 10,000 and can be over 100,000. Wow. And the cells, of course, are blasts. Blasts can be lymphoblasts or myeloid blasts. Myeloid blasts are subdivided into myeloblast and monoblasts. Cool.
When you do a bone marrow biopsy, again, you will see these blasts. Blasts constitute more than 20% of the bone marrow. Usually, the bone marrow is completely replaced by these blast cells; that's why it's tender. As for acute leukemia, we need the lab, of course. We need morphological analysis, which is the peripheral blood smear to see these ugly, large blasts. We need cytogenetics studies or karyotyping, as we will discuss later. We need molecular marking and we need cell surface marking; cluster of differentiation or CD. How does the police recognize you? By showing your ID. How do we recognize these malignant leukemic cells? By showing their CDs. Then we have cytochemical analysis by periodic acid-Schiff, peroxidase assays, and Sudan blood stain.
To treat acute leukemia, we have the induction phase and the consolidation phase. What's the induction phase? Also known as remission induction phase. So when the disease goes away and you are fine, we call this remission, and you are happy. When the disease comes back, we call this relapse. So remission and relapse are different. Remission means the cancer is gone, and we are happy, so we call it remission induction. We'd like to induce the remission of these cancer cells. We do this by high-dose chemotherapy. They suppress all of the cell lines; okay, pancytopenia is going to occur, and the patient is prone to infections, okay, especially neutropenia. Okay, we can give them myeloid growth factors. They reduce the length of hospitalization, but they do not increase survival. In other words, they increase longevity, but they do not decrease mortality; decrease morbidity, but they do not decrease mortality. These growth factors, okay, support your cell lines; okay, they help you form red blood cells; okay, they help you form white blood cells, and you can get red blood cells and platelets, of course, because pancytopenia is bad. This is the remission induction phase, which is phase one. Now, in many cases, the cancer is gone, and the patient is so happy, and they think, "Oh, I don't need to go to the doctor again." Wrong, because sometimes the cancer comes back; that's why we need a consolidation phase. When the cell count normalizes, i.e., remission, cancer cells are gone, we use consolidation therapy to prolong remission so that we don't relapse and to increase survival. We can sometimes use gene expression profiling or DNA microarrays to predict the prognosis and guide therapy; is the patient improving or not? To monitor the therapy, but the treatment of leukemia: induction phase, consolidation phase. In some cases, we may use radiation if it's a lymphoma, for instance, or in other cases, we can use bone-marrow transplant, but we keep this for the young patients.
Forget acute leukemias. Means more than 20% blasts in the bone marrow. By definition, acute leukemia is blasts greater than 20%. Don't ever forget this. You're done. Go enjoy your lemonade. Okay, I don't think you will ever drink lemonade again because you will think of leukemia all the time. Anyways, I'll see you next time. Be safe, stay happy, and study hard. Thank you.