Transcription
Hey guys, it's Medicos Perfection. Elsewhere, finally medicine can make sense. And today we're going to talk about treatment options for myelodysplastic syndrome, or MDS. Let's get started. [Music]
As you know from my previous video on MDS, MDS is a heterogeneous group of hematologic disorders. They are characterized by cytopenias such as anemia, thrombocytopenia, leukopenia—called pancytopenia. Also, there is a risk for transformation to acute myeloid leukemia. MDS can be low risk with marrow failure, can be higher risk with transformation to AML, or can have myeloblasts and chromosomal abnormalities. The bone marrow can either be normal or hypercellular—most cases are like that—or hypocellular in a minority of cases. Please don't forget: MDS = dysplasia + cytopenia. And here is our famous slide of hematopoiesis and myelodysplasia. There is dysplasia of the myeloid lineage. Also, I've told you before that MDS is an intermediate stage between normal and acute myeloid leukemia. That's why the entire purpose of treatment is to try to delay this process of transformation into AML.
Regarding the prognostic factors, we have favorable prognostic factors and unfavorable prognostic factors. Favorable include 5q deletion, 20q deletion. 5q is very high yield; why? It's commoner in females, it has thrombocytosis with good prognosis, also it can be treated with a drug called lenalidomide, as we will discuss soon. Unfavorable prognosticators: increased percentage of blasts, increased number of cytopenias, increased age, cytogenetic abnormalities such as chromosome 7.
The treatment options for myelodysplastic syndrome include supportive therapy, human growth factors, chemotherapy, or stem cell transplant. So let's memorize them together. What is the last resort for treatment of new leukemia? Stem cell transplant. What is the name of the drugs that treat cancer? Chemotherapy. Okay, now let's help support this bone marrow because it has pancytopenia. Let's boost the cell production, so let's use growth factors to help platelets, red blood cells, and white blood cells mature. These are called growth factors; they help them grow. Also, if there is no hope, instead of telling the patient, "Go to hell, there is no hope for you," we offer supportive therapy, because, as you know, doctors are compassionate human beings.
Before we discuss the treatment options, here are some general rules. MDS treatment depends on the type of MDS, such is the classification—the WHO classification. Prognosticators: we have favorable and unfavorable, age, health status, etc. If there are no symptoms and the lab is normal, no treatment. If the patient is elderly, probably MDS is incurable; offer supportive therapy instead of telling him, "There is no hope for you." Stem cell transplant is the only method to potentially cure MDS. If there is 5q deletion, use lenalidomide, as I've told you. Advanced MDS with a high chance of progressing to AML, give chemotherapy.
Now let's discuss the four treatment options. First, supportive therapy offers symptomatic treatment. Okay, to treat anemia, give erythropoietin, human growth factors that are similar to EPO. If they fail, give blood transfusion, but when we give blood transfusion, we risk iron overload, so stop the iron supplements and do iron chelation with drugs such as deferoxamine and the great oral drug deferasirox. If you pay close attention, both of these drugs contain FE, which is iron. Hello. For thrombocytopenia, give human growth factors for platelets, platelet transfusion. If both of them failed, try aminocaproic acid. For leukopenia, give human growth factors for white blood cells.
Second, the growth factors, or human growth factors. Okay, growth factors for red blood cells to help treat anemia: use erythropoietin, which is similar to erythropoietin, or darbepoetin alfa. To boost platelets, use romiplostim or eltrombopag. Notice eltrombopag; it helps the thrombocytes. Thrombocytes, of course, are the platelets. These agents are called thrombopoietin receptor agonists. There is a drug called oprelvekin; it's an interleukin-11. Looking at interleukin raises platelet count after chemotherapy, but not in MDS. Okay, I've just mentioned it because it's very similar to the thrombopoietin receptor agonists. White blood cells: how to boost them? Granulocyte colony-stimulating factor or granulocyte-monocyte colony-stimulating factor. Go back to my slide on hematopoiesis to know the difference between granulocytes and monocytes. Granulocytes colony-stimulating factors such as filgrastim.
Next, anti-cancer drugs called chemotherapy. We have four different categories. First, hypomethylating or demethylating agents. They remove methyl groups. They are pyrimidine analogues. They help MDS cells mature instead of being useless, dysplastic, ugly, hypermethylated. Agents include azacitidine or decitabine. Side effects of these drugs: early in the process, you can get cytopenias, as pancytopenia. Standard chemotherapy: we use it for high-risk MDS patients, such as decitabine. You can add idarubicin or daunorubicin. Side effects of decitabine: it trashes your brain, giving you balance problems, dizziness, etc. Idarubicin and daunorubicin: they treat your heart miserably; they can lead to cardiomyopathy. Immunomodulating agents such as lenalidomide for the 5q deletion subtype of MDS. Side effects of lenalidomide: deep vein thrombosis and it's teratogenic. If you recall, there's a drug called thalidomide used to treat multiple myeloma. Sometimes lenalidomide is teratogenic. Thalidomide, lenalidomide, both of them are teratogenic. Make sense?
Last, we have immunosuppressants. They are used for the hypocellular bone marrow in the rare cases of MDS, because most of the time the bone marrow is either normal or hypercellular; in the minority of cases it's hypocellular. In these cases, use immunosuppressants such as antithymocyte globulin, ATG, or cyclosporine. Of course, cyclosporine trashes your kidney.
Fourth, stem cell transplant. Let's be honest, it's the only potential cure for myelodysplasia. So how do we do a stem cell transplant? First, we destroy the bone marrow, then we give the patient stem cells. So first, destroy the bone marrow with chemotherapy or radiation. Side effects, of course, pancytopenia. Both chemotherapy and radiation can lead to cytopenia. Then we give the patient stem cells, so the bone marrow is happy because these stem cells are hematopoietic; they are capable of producing new blood cells. There is a risk here of graft-versus-host disease. What is that? This is the question of the day. Please let me know down in the comment section.
Okie dokie, let's summarize. Treatment options for MDS: supportive, human growth factors, chemotherapy, or stem cell transplant. General rules: no symptoms, no treatment; elderly patient, supportive therapy only; stem cell transplant is the only method to cure MDS. If there is 5q deletion, use lenalidomide—don't forget this is teratogenic. Advanced MDS with a high probability of progressing to AML, please give chemotherapy.
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