Transcription
The previous video we have discussed acute lymphoblastic leukemia. Today let's talk about how to treat acute lymphoblastic leukemia. And yes, this is true: you can treat this type of cancer in most of the cases.
How to prevent ALL? There is some evidence in some studies, but not all of them, giving folic acid to the pregnant mother can decrease the incidence of ALL in her newborn, which is pretty cool. Give me folic acid; don't be such an alcoholic. #nocancer
How to treat ALL? As I've told you before, chemotherapy. We have induction phase, consolidation phase, followed by maintenance for ALL. Since the incidence of CNS involvement is high, we need prophylaxis for CNS and sometimes for the testes. Okay.
Rameshan: Induction—why? To decrease blast cells into undetectable levels and to restore the normal marrow function. #completeremission. There are two problems during this phase: resistance and infection. When the patients are cancer-free, sometimes they say, "Okay, I'm healthy now. Thank you, doctor. I will never come to see you again." Wrong. You will come to see me again, and you need more chemotherapy. Please. Why? Because sometimes the cancer relapses, comes back. So why consolidate? Because relapse occurs in almost 100% of the cases—all of them. So we need consolidation and maintenance therapy. Okay.
Why prophylaxis for the CNS? Chemotherapy usually cannot penetrate the blood-brain barrier effectively. Thanks to astrocytes forming your blood-brain barrier, and it cannot penetrate the blood-testis barrier effectively. Thank you, Sertoli cells, for forming such a barrier. But before starting chemotherapy, we should stabilize the patient. We should make sure that the patient is fine and ready for chemotherapy, or a chemotherapy candidate. To stabilize the patient: if the patient has thrombocytopenia, give them platelets; if they have fever and granulocytes < 0, do blood cultures and give them antibiotics; if they have leukostasis, do local pheresis. Local stasis sometimes can be an emergency. You should prevent tumor lysis syndrome by hydrating the patient and giving them allopurinol. What is tumor lysis syndrome? Here is your cancer cells; you're giving chemotherapy to destroy the cell, but you have lots of cancer cells. These cells are going to get destroyed at the same time, releasing a lot of stuff inside them. I've told you before: any electrolyte that's inside the cell more than outside, start with a P, such as phosphate and potassium. These are more concentrated intracellularly than extracellularly. When these cells rupture, lots of potassium in the blood, lots of phosphate in the blood, and you have a nucleus because white blood cells have a nucleus, so you'll end up with lots of uric acid, and all of these are terrible for your kidney. That's why we need to hydrate and give allopurinol to prevent uric acid formation.
Now the patient is stable and ready for chemotherapy. First phase: induction phase. How? In ALL, you give prednisone plus vincristine. Some people will add daunorubicin; some people will add L-asparaginase; some people will add cyclophosphamide. Okay, but if you'd like to make it easy, just remember prednisone and vincristine. Then consolidation, followed by maintenance. Consolidation by high-dose methotrexate, cyclophosphamide, etc. Maintenance again by methotrexate and 6-mercaptopurine, low doses. Prophylaxis for the CNS: giving intrathecal methotrexate. Sometimes we add cranial radiation. For the testes, we radiate and sometimes we give chemo. Ask the patient if he would like to freeze his sperm in a sperm bank before starting therapy because it will lead to infertility. Last resort is bone marrow transplant.
If the patient with acute lymphoblastic leukemia has this translocation, which is the Philadelphia chromosome (9;22) translocation, we give them a tyrosine kinase inhibitor for treatment. Tyrosine kinase inhibitor—a drug that ends in -nib, such as imatinib. Later on, when we discuss chronic myelogenous leukemia, again they have this t(9;22) translocation, and guess what the treatment will be? Imatinib.
Locations of ALL treatment will give them chemotherapy, which will lead to tumor lysis syndrome, as I've told you: lots of potassium, lots of phosphate, lots of uric acid, leading to acute kidney injury, historically known as acute kidney failure, but since we don't like failure, we call it now acute kidney injury. Plus, it's not actually failing because it recovers, so that's okay. Then we have the direct testicular radiation, will lead to permanently low testosterone, so consider sperm banking before radiation. After radiation, there will be no sperm. Okay. Then intrathecal methotrexate plus intracranial radiation; they have complications such as neurocognitive dysfunction. So the leukemia itself can lead to neurocognitive dysfunction; treatment for leukemia also can lead to neurocognitive dysfunction. So this is a tough situation. And high-dose methotrexate can lead to something called acute leukoencephalopathy.
ALL is a cancer that has high cell turnover, will lead to folate deficiency, leading to macrocytic anemia; increased uric acid leading to kidney injury, sometimes kidney stones; okay, may precipitate gout. Okay, but gout and high uric acid are not the same. Increase potassium—bad for your heart, causing arrhythmia; and increasing phosphate also bad.
My heroes are ready to answer this case. We have a 76-year-old female coming to you complaining, "My legs are swollen; I'm tired all the time." So you order some labs. The hematocrit is 25%, which is low—this is anemia; white blood count of 40,000—this is leukemia; platelet count is 99,000—this is thrombocytopenia; peripheral smear shows circulating lymphoblasts greater than 20%—this is acute leukemia. Okay. Then bone marrow biopsy confirms the diagnosis with this translocation of 9;22—Philadelphia positive ALL. Okay. She asks you, "What therapy should I get?" You answer: A. You should be fine; go home and enjoy life. Or B. I'll treat you symptomatically only. Or C. Prednisone, vincristine, daunorubicin, L-asparaginase, as if it's just a normal case of ALL or a regular case of ALL. Or D. Dexamethasone plus dasatinib or thalidomide, melphalan, and prednisone. Okay, so C is correct. If it was ALL with negative Philadelphia chromosome, E will be the answer. If this is multiple myeloma, okay, you should be fine; go home and enjoy life. No, this is wrong. She has leukemia, acute leukemia. This may be correct in cases of CLL stage zero. I'll treat you symptomatically only. No, baby, she has cancer. Look at the numbers; these are terrible. So you give her dexamethasone plus dasatinib. This is the correct answer because she has the t(9;22) translocation, Philadelphia chromosome, treated by a tyrosine kinase inhibitor—anything that ends in -nib, such as imatinib or dasatinib. So D is the correct answer, guys. You're the best. I'll see in the next video. Please subscribe; please share my videos. Until next time.