Transcription
Hey, it's Medicos Perfection Alice. Today's topic is acute lymphoblastic leukemia. It's a series in hematology and oncology. If you haven't already watched my previous videos, the chances of you understanding anything in this lecture is zero. Okay, so the series is to be watched in order. Welcome again. It's Medicos Perfection Snails.
Now, acute lymphoblastic leukemia: it's acute, so the patient is younger; it's lymphoblastic, so the cells are younger, more immature. Cool. And lympho means they are of the lymphoid cell lineage; leukemia means blood cancer, or technically it's a bone marrow cancer since these blood cells come from the bone marrow. So you will have abnormal blasts in the bone marrow and in the blood.
What's unique about ALL is that it's the most common leukemia overall, and it's the most common cancer in children. Not just saying it's the most common leukemia in children; it's the most common cancer in children. That's why it's very important. It's common in patients with Down syndrome, or trisomy 21. Okay, they are predisposed to acute lymphoblastic leukemia. And these are your old, ugly, immature, large blast cells—lymphoblasts, to be more specific, for the hundredth time. You have leukemia: acute and chronic; ALL, AML, CML, CLL. L here stands for lymphoblastic because it's acute, immature cells; L here for lymphocytic—cells are more mature. There is your hematopoiesis: okay, multipotent stem cells, myeloid and lymphoid cell lines. Lymphoid will give you lymphoblasts, and myeloid blasts will give you lymphocytes and natural killer cells. Lymphoblasts here lose their ability to differentiate but retain the ability to replicate. That's why it's a bad cancer; we are stuck with these large, ugly, immature cells called lymphoblasts.
The risk factors for ALL: antineoplastic agents, also known as chemotherapy; ionizing radiation; Hodgkin's lymphoma; benzene exposure; and multiple myeloma. ALL is an acute leukemia—surprise, surprise. Acute lymphoblastic leukemia, so it's acute leukemia; therefore, the patients are much younger, the cells are less mature—blasts. More than 20% of your bone marrow; younger patients, especially between birth and 14 years old. I know ALL has bimodal distribution; it can affect adults greater than 14 years of age, but then it will have poor prognosis. But I would like you to concentrate on this age.
Then we have the lymphoblasts. Describe the lymphoblasts: no granules because lymphocytes are non-granulocytes, as you know. So lymphoblasts will have no granules, okay, like father, like son. Increased nucleus-to-cytoplasmic ratio. If you see here, there is a very little cytoplasm left; we call this candy cytoplasm. The nucleoli—not the nucleus—the nucleolus is less prominent than in myeloid blasts. That's cool. These lymphomas proliferate and will do three things: replace most of the bone marrow—you end up with pancytopenia; they will enter the peripheral blood—increase blast in the blood will lead to local stasis, which is bad; metastasis through the body—hepatosplenomegaly, generalized painless lymphadenopathy, testicular enlargement and infiltrate, and infertility. And then you have headaches, and you have bone pain, and also some skin abnormalities. Tenderness over the sternum is a sign of leukemia. Kind of knew all of the stuff from the previous lecture. Okay, what else do we need to know?
ALL is positive for something called terminal deoxynucleotidyl transferase; it's a DNA polymerase. Okay, what else? It's periodic acid-Schiff, or PAS, positive. So ALL is TdT positive, PAS positive. This is very important for any exam. Okay, they are common in trisomy 21, or Down syndrome, and these are your lymphoblasts. ALL is classified into pre-B, B, and T. Other sources will have pre-B and B pretty much. I'm so confused looking at different textbooks, but I really don't care. Okay, it's just a classification, but here is what you need to know. Pre-B ALL is common in children, especially Down syndrome. Since this is a B lymphocyte, it will be CD19 positive and CD20 positive, and I've told you this before, and also it will be CD10 positive. We call CD10 CALLA—common acute lymphoblastic leukemia antigen. Cool. This is only with the B, not with the T.
What translocations are there? T(9;22) has bad prognosis, and t(12;21) has good prognosis. I have a mnemonic for this: this is 12;21, so it's a mirror; mirror occurs in minor, which means children, and the prognosis is minor, which is a good prognosis. It's not terrible. Then you have the B-cell ALL; can have t(8;14), and now we call it Burkitt's leukemia. Okay, the t(8;14) translocation is also present in Burkitt's lymphoma. Here we have the T-cell ALL. We have an adult, usually young adult in his 20s, with mass in the anterior mediastinum, which can lead to a pleural effusion, respiratory distress, or superior vena cava syndrome. This is a T-cell; it will be CD3 positive, and you can have CD7 positive as well. If it's a T-cell, there's a role; can be three, four, five, six, seven, eight, but not ten. Ten is for the B-cell.
Some factors will carry a poor prognosis for patients with ALL; we call them the unfavorable prognosticators. Okay, when you find this, okay, usually the response to chemotherapy will be poor, and you should consider bone marrow transplant as an option. Here are your unfavorable prognosticators: old patients. I've told you ALL is a disease of the young; it's acute. If it comes to patients greater than six years of age, it has bad prognosis. If the white blood cell count is greater than 100,000, of course this is bad—more cancer cells and poor prognosis. Mature B or early T-cell types. Again, the one with good prognosis is the pre-B; if it's mature B, that's bad prognosis; if it's early T, that's bad prognosis. If it has the Philadelphia chromosome translocation t(9;22), it has a bad prognosis. Don't confuse this with the Philadelphia chromosome translocation in CML; in CML, this translocation has a good prognosis, but here it has bad prognosis. And of course, you have translocation for eleven, or MLL-AF4 fusion gene. Okay, if you don't have enough time, just memorize one, two, and four. But if the patient has good prognosis, such as a kid with pre-B subtype and also with t(12;21), the mirror translocation, you can give chemo; the response is greater than 80 percent, which is amazing. We can cure cancer by greater than 80 percent probability; it's amazing.
Diagnosed acute leukemia: you need the lab; you need the morphological analysis, which is the blood film or the peripheral smear, and he will see lymphoblasts. Inside of the next studies: karyotyping, to take this t(12;21), which I called the mirror, which has minor prognosis, which is good prognosis, and the t(9;22), Philadelphia chromosome translocation, which has bad prognosis. Also, you need molecular markers; you need the CDs. Again, the police identifies you by your ID; we identify the leukemia cells by their CD. If it's a T-cell origin, you'll find CD3, four, five, six, seven, or eight positive; it's a B-cell, will have CD10, 19, or 20. We call CD10 CALLA. Cytochemical analysis: ALL is PAS positive, TdT positive, and histidase negative.
Let's go to the lab: peripheral blood smear and bone marrow biopsy. On peripheral blood smear, you have normocytic or macrocytic anemia—why macrocytic? Due to folate deficiency as a result of the rapid cell turnover in leukemia. You can have thrombocytopenia. White blood cell count can range from less than 10,000 all the way up to greater than 100,000, and you will have lymphoblasts in the peripheral smear. Describe lymphoblast: medium size, but it's larger than the lymphocyte; a granular; scanty cytoplasm; increased nuclear-to-cytoplasmic ratio. On bone marrow biopsy, the marrow is hypercellular; blasts greater than 20 percent, usually completely replaced by this ugly lymphoma, like this. That's why the sternum is tender.
Acute leukemia: by the induction phase and the consolidation phase, followed by maintenance. Since ALL is common in the CNS, causing headache and other neurological abnormalities, we need CNS prophylaxis because this chemotherapy has poor penetration to the brain, thanks to your great blood-brain barrier.
Try to answer this case: so what do we have? We have a nine-year-old male with 47,XY. Normal males are 46,XY, or you can say 44+XY, but this is abnormal. Okay, this is probably trisomy, which trisomy I don't know until this moment. Comes in with fatigue, mucosal bleeding. You order some tests and find out that the bone marrow blast cells represent more than 20% of the marrow; the white blood cell count is 50,000. This is leukemia. Parents refuse chemotherapy. So we have a kid with leukemia, and we have a chromosomal abnormality. Probably this is what this is: ALL in Down syndrome. I've told you the chances of success rates in chemotherapy is greater than 80%, sometimes 90% or more, but the parents refuse to treat their kids. First, what's the diagnosis? ALL. This is it. What should you do next? Should you let the patient go home? Should you admit patient against the will of his parents? Should you obtain a court order to start chemotherapy? And the answer is: obtain court order. Why is that? Let's go from a medical perspective and let's go from a legal perspective.
From a medical perspective: do no harm. Leaving those patients without chemotherapy is going to harm him because most probably he is going to die very quickly, and the chances of success in chemotherapy is around 90%. Okay, so the odds are great. Okay, we should get a court order to start chemotherapy even if his parents declined. Now, what's the legal perspective? I'm not a lawyer; I'm not a doctor either, but it's called an externality, which means leaving this patient alone will lead to death; it's an externality to the parents. Okay, they shouldn't control other person's life, so it's called an externality, so we should obtain a court order. Okay, if it was vaccinations—so patients are refusing to give their kids vaccine—you will let them have it. Okay, you will never give the patient vaccines against his parents' will. What happened here? Because the chances of the kid, for example, getting measles without the measles vaccine, I don't know, but it's not 90 percent. The chances of the kid infecting other kids is not 90 percent at all, so the externality is very low. That's why in this case we have to respect the parents' wishes.
We have another question: 21-year-old male comes in with fatigue, mucosal bleeding, testicular enlargement. You order some tests and find bone marrow blast greater than 20% of the bone marrow; white blood cell count is 50,000. This is probably ALL. Okay, the patient is single and would like to have kids in the future. What should you tell him? A: advise him to preserve his sperm in a sperm bank before chemo and radiation because they will damage the testicles; start chemo and radiation immediately; consult the hospital's ethics committee. The answer is A: advise him to preserve his sperm in sperm banks because chemo and radiation to the testicles will lead to irreversible infertility most of the time.
All set. Now you know everything you need to know about acute lymphoblastic leukemia. Please subscribe and please share this video. If you'd like to subscribe to my Patreon page to help me produce more videos in the future and to get early access, it will be great, and I'll thank you so much. See you then.