How do you distinguish between a diagnosis of myelodysplastic syndromes and acute myeloid leukemia?

How do you distinguish between a diagnosis of MDS and AML?

So AML is a disease that either can come on by itself. So we have patients with newly diagnosed AML or they can come from what's called the progression of MDS. So you can have MDS for a while and then it becomes AML. AML itself is a disease where I would say it's an aggressive, fast-growing disease, whereas MDS can be a much slower-growing disease. It's a fast-growing disease and it can lead to a series of problems. One is your all your blood counts are going to be low, so you have all the same problems. The other is just a few of many leukemia cells in your blood. Your blood can become very thick and sluggish. And so you can have things like strokes, you can have things like problems with the breathing because the blood just can't get through there. That's something called hyperleukocytosis and so that is truly an emergency. Once you develop AML and so it can be treated with a bunch of different things, typically it's with high doses of chemotherapy. It converts something from what I would say a chronic condition to something that's very acute. So if you had AML and we didn't do anything about it, my guess is that you will probably die of AML within 6 to 12 months, like it's an aggressive condition. And so once you go from MDS to AML, there's obviously can be a pretty abrupt shift in the way that we take care of you. Right. We're not maybe we don't do hypermethylation agents, maybe we do high dose chemotherapy. Now, maybe we were thinking about doing a bone marrow transplant, but now you have to have a bone marrow transplant. We're not going to cure you with chemotherapy. So I think that it is, it really is an unfortunate sort of at the end of the line type of thing for a lot of patients. And it just changes your treatment, it changes your prognosis, it changes how we approach things, how we approach patients. So I think it really is an extension of MDS, but it's really almost like a different disease. If you have MDS and then go into AML. These official designations based upon the percentage of blasts you have, whether you have 20% blast, where you have 30% blasts. But you have to think about it. It's not like one day you have 29% and you have MDS and the next day you have 30 and now you're AML. It's all on a continual. And so I would say like I get pretty worried when people get above 20% and they're starting to climb up, I would say, look, I'm not going to wait until you get AML. I'm going to treat you like you have AML now. Right? Because I can tell you're getting there. And I would rather treat early or not. I do a bone marrow transplant at that stage and not wait until you get to AML, because once you get to AML, it becomes harder to treat. And so you want to sort of watch it as it goes. Well, some people will have blast counts and they just stay the same for years and years and years. You know, not to worry about it. But I think that that's really the harbinger is looking at the blast code that and every once in a while you can resequence and see if there are additional mutations that come up that maybe will push you along. I think those are the two standard ways of looking at.

What signs should my doctor and I be looking for to watch for MDS progressing to AML?

High risk MDS is definitely one that is going to has a very high propensity to progress. And I would say, well over half the patients are going to progress to AML. I think that if you have low risk patients, the likelihood of them getting to higher to AML I think is much, much lower. And so I think it depends on kind of whether you have high or low risk. The other thing I would say is that an important thing that we do in MDS is that we have these abilities now to sequence every gene in a cell. And so there are probably only about 400 to 600 genes, which are really important in MDS and then AML. So if you get worked up for AML, an important part of that is you need to get those genes sequenced and see if there are mutations there. Some of those mutations are clearly associated with moving to AML very much, much more quickly. So I think having that genetic information is important and one needs to ask for that when need to get that when you're initially getting worked up. It's like looking at your blood counts are the biggest thing. Are they high, low? And then at some point you're going to potentially see blasts in your blood. So that's a good indication that you can follow it. You might want to do a bone marrow at that point to really see what the blast count is in the blood, to reach to read sequencing, sequence again. See if there are other mutations. And, It's something where I think most of it is derived from what your blood counts are. So in most patients we just religiously check people's blood counts every month or every two months or every three months or every couple of weeks. So a lot of it is driven by your counts. Typically in low risk MDS, it's almost always you only have anemia. Anemia is the first sign. And so that you may have issues just with anemia. When you get to higher like high grade MDS, almost universally, all of the blood counts are low. But there are things in between where you could have like low platelets and low red blood cells. But normal white blood cells, you could have normal platelets, but low red blood cells and low white blood cells. But in general, early on it's really just anemia. And then later on in high risk disease, it is going to be almost always all three types of white blood cells are going to be low. The main way to distinguish between AML and MDS is by the bone marrow blast percentage. If there's 20% or more bad cells, there are other factors that can help differentiate it. There are certain mutations that are specific to AML that will sometimes see in MDS, and now we call those patients who have those mutations with a certain profile in the bone marrow as also having AML. Usually we can see it in the blood counts. So when the blood counts drop or when the white blood cell count goes up very high, if that would be a sign of MDS progressing to AML. Additionally, one would feel the symptoms related to low blood counts. So if someone had previously pretty good blood counts with their MDS and now they've progressed to AML, their bone marrow might not be functioning as well. And so they could have a low hemoglobin with anemia and anemia related symptoms, including fatigue, shortness of breath, as well as low platelets with low platelet related symptoms, including easy bleeding and bruising.