MD Anderson Cancer Center
Lisa Garvin: Welcome to Cancer Newsline, [background music] a podcast series from the University of Texas, MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research and diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today, we'll be talking about a form of leukemia known as acute myelogenous leukemia or AML and here to speak on that is Dr. Guillermo Garcia-Manero, he is a professor in the Leukemia Department here at MD Anderson. Welcome Dr. Manero. Let's first talk about leukemia and itself 'cause I think we have to distinguish between chronic and acute. So what is acute leukemia?
Dr. Guillermo Garcia-Manero: Okay, so this is interesting question because even medical students get confused with this concept. So leukemias in general are cancers of the blood or of the bone marrow and there are multiple types. The same way you have brain tumors, lung cancer, et cetera. Traditionally, I guess when people were starting to think about these diseases, they realize that they were leukemias that once the patient presented with it, he or she was going to be dead in the next, you know, few days, few weeks. That's acute leukemia. And then the physicians saw all the group of patient that had abnormal blood cells but they live for it longer, those are chronic. But the reality is that there is significant--so this is a very archaic way of thinking about diseases but it's the term that we use.
Lisa Garvin: But generally--I'm sorry. Generally, you can say though the chronic leukemias progress slowly and acute leukemias come on more aggressively and more quickly, is that safe to say?
Dr. Guillermo Garcia-Manero: Yeah. So--that's exactly right. But then those acute and chronic leukemias are really then divided into different types that are--that originally were based on morphology of the cells, what we call the lineage of these cells that are by and large either from myeloid origin that is one subset of white cells in the blood, or lymphoid that this another. So for instance, a neutrophil that is something that maybe most people were familiar is a myeloid type of cell. A lymphocyte is a lymphoid type of cells. Now, these lymphoids can get also rise to lymphomas or to multiple myeloma, so these three gets more complicated. But you have lymphoid leukemias, you have myeloid leukemias, and then depending on how fast they will get the patient sick or how fast they will develop, then they are called acute and chronic. So then you have acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphocytic leukemia. So these are just right there for very simple ways to think about these diseases.
Lisa Garvin: And since we're talking about AML and let's kind of start at the beginning. Who is most likely to come down with AML?
Dr. Guillermo Garcia-Manero: All these diseases are diseases of aging, so most patients with AML are older individuals, the same thing for myelodysplastic syndrome, the same thing for CLL of chronic lymphocytic leukemia. And then acute lymphocytic leukemia is also a disease of aging but it follows a different peak because this is the disease that is the most frequent type of tumor in children. So there are some specific subsets of these patients. But these are the diseases that in general would be associated with aging. Now, not all of them follow the same chronological pattern. So for instance, it is very rare to see young patient with MDS. I see a couple a year, we see children with AML. So there are different subsets but by and large, the largest group of patients affected by these disorders will be people older than 60 years of age.
Lisa Garvin: And I think we hear, you know, I've heard the story over and over again with patients I've talked to that acute leukemia can come on like a flu. It come on--comes on pretty quickly. How it manifests itself fairly quickly, does it not?
Dr. Guillermo Garcia-Manero: Yes and that's actually where the age may make a difference because for instance, that very abrupt, very acute way of presenting is most commonly observed in the younger group. Whereas the older group, it usually presents more like a myelodysplastic type of presentation where the counts are low.
Lisa Garvin: And what sort of symptoms do we see? Fatigue--
Dr. Guillermo Garcia-Manero: Well, depends on how far these are. So let's say one of these early patients that you are talking about, younger, the disease is very fast. That person is likely to have fever. That person is likely to have very severe bruising, very severe fatigue, you know. Traditionally, gamma filtration was a way that we will see patients with leukemia where the leukemia goes to the gums and sometimes the dentist will make this diagnosis. That's for specific types of leukemias fast growing, so fatigue, malaise, weakness, fever. Many times, unfortunate patients may present to the hospital already, you know, lung failure because the leukemia cells are in the blood, they tend to infiltrate tissues. So it's not uncommon that you'll have liver dysfunction, kidney dysfunction, sometimes heart dysfunction, it can go to the brain. So many times when the patients present, they really have multisystem organ failure just because all the organs are affected. But the reality is that right now, most of our patients really present with this kind of like MDS type of picture, particularly the older ones. So they are being diagnosed earlier and earlier. And the symptoms are not so specific so they may have some bruising, they may have had some infection that triggers this, they may not have felt well over the last few months, but there is not one cardinal feature that you say, "Oh, I have leukemia."
Lisa Garvin: How often do you--well, I don't know if I want to ask the staging question but how often do you catch AML early? I mean, are people like--a lot of people I hear say they have flu-like symptoms which a lot of people will blow off quite frankly. So do you tend to get people who are kind of--they have progressed pretty far before they've come to see a doctor?
Dr. Guillermo Garcia-Manero: Well, so there are two issues here. One of course is socioeconomic and educational status of the patient. So some patients may let go their symptoms for a longer period of times. And then by the time they come to you, said, "We'll, for how you'd being feeling like this," and say "Well, you now, weeks or months." Some other people may have been more aggressive. So this depends on those factors. And then the reality is that the disease has very specific molecular features. And so there are no stages per se but so it's a bit different from what we were talking earlier in MDS 'cause this is either you have it or you don't have it. But these are also heterogenous and they are subsets that behave in different ways. So for instance, there are types of leukemia called acute promyelocytic leukemia or APL where the patients can have a high tendency to spontaneously bleed. Well, they may have a different presentation than other subsets. So there are different types of leukemia by sectioning and we know that different cytogenetic and genetic lesions. So the presentation is not so much related to the stage per se, but to the biology of the disease. And that's why scientists have always been interested about this disorder that this different biologies with very distinct clinical presentations.
Lisa Garvin: How likely is this to be caught, you know? Obviously in a yearly physical exam, they do a complete blood count. Would it fairly easy to see AML in a typical blood count?
Dr. Guillermo Garcia-Manero: Yeah because the CBC that shows hemoglobin, platelets, white count will be abnormal. But sometimes, actually, it's not obvious. So let's say you're a little bit older and you have a little bit of anemia and then, you know, the doctor said "Well, you know, you maybe--this maybe because you're a little bit older."
Lisa Garvin: Yeah, here, take some iron pills, you'll be fine.
Dr. Guillermo Garcia-Manero: Something that. So it depends. Of course, some, you know, most doctors are good and they not only look at the labs, they'll look at the person and see if something else is going on on a particular person. But the reality is that this are question that patients ask all the time. And nowadays, you know, we have--people keep their records, they have their labs and they go back and they said, well, did I had this six months ago.
Lisa Garvin: What is the morbidity and mortality on it? Do you--just ballpark figures. We don't need exact figures. I mean, in terms of how many diagnose and how many actually succumb to the disease in a year?
Dr. Guillermo Garcia-Manero: So the overall survival rate of AML in the younger subsets. So traditionally, we thought about this disease into patients younger than 60, older than 60. So in patients younger than 60, the overall survival rate like long term survival is about 30 percent. In the older, this number drops significantly, prognosis of older AML changes. But now we actually know a lot about how we can actually prognosticate these patients based on kind of simple cytogenetic and molecular features of the disease. So for instance, chromosomal analysis that is virtually done by everybody right now when we assess these patients has a very significant impact in our, you know, capacity to prognosticate these patients. So there are patients that have what we call very complex cytogenetics particularly if they have an alteration of chromosome 7. They have very poor prognosis with actually most conventional therapies that we have. But then there are patients that have very good features. For instance, if they have something we call core binding factor abnormalities that are sometimes referred to as inversion 16 or translocation 8;21. These patients actually have survivors that go from 50 to 60, 70 percent. And then this type of bleeding leukemia I mentioned earlier, this APL or acute promyelocytic leukemia. Right now, there are actually two therapies developed here by the leukemia department, have a survival that is probably to an 80 to 90 percent depending on the risk. So it's not universal. So you cannot say, okay, just because you have AML you have 30 percent survival or at a 10 percent survival. You really have to look into, right now, the cytogenetic and molecular features of the disease because again, there's heterogeneity. There are some groups of patients that I feel pretty confident that we can tell them, you know, they have almost 90 percent cure rate, let's say low risk acute promyelocytic leukemia. And unfortunately, there are others that it's going to be very hard to actually make them live more than one year. The group we are struggling right now are patients that are older and this is important because these are the most frequent, and patients with bad or poor risk cytogenetics. And then if on top of that and this actually they tend to cluster, if you are older, with this molecular or cytogenetic features prognosis is very poor. So the spectrum can go from a very young patient with very good molecular features cure rate could be 80, 90 percent. To the element of the spectrum where you have an older person and the rate is 90s, we see people here with very poor risk cytogenetics where survival will be days, month, weeks.
Lisa Garvin: We've seen with chronic leukemias that Gleevec was practically a miracle drug. I mean, it did so well and really increased the outlook for a lot of patients. Is there a similar drug for AML that you all are looking at?
Dr. Guillermo Garcia-Manero: This is a fantastic question because Gleevec works in this group of patients to have this specific alteration called the Philadelphia chromosome BCR-ABL gene. And it happens that most patients with CML have this particular alteration. So CML is very homogenous disease. AML is very heterogenous. But for instance, there's a subset of patients with AML that this acute promyelocytic leukemia patients I referred earlier, they are characterized by a specific translocation sort of being called Philadel--
Lisa Garvin: Which means genes have swapped places?
Dr. Guillermo Garcia-Manero: Well, pieces of chromosomes.
Lisa Garvin: Well, have swapped.
Dr. Guillermo Garcia-Manero: So instead of being the Philadelphia chromosome or 9;22, they have an alteration between this chromosome 15 and 17. It involves two genes called PML and RARa fusion gene. Now, in that disease, we don't have a Gleevec but we know that for instance it would treat with these two drugs called all-trans retinoic acid and arsenic trioxide that actually are not chemotherapies, these are biological agents, we easily can cure 70 to 80 percent of patients that come to see us and depending on the risk even higher than that. So this is another example of how molecular evaluation of these patients may actually lead to really incredible outcomes. What is interesting actually is that these patients 15 years ago, they had probably one of the worst prognosis because as I mentioned earlier, they tended to bleed. And now we know their molecular features, by chance we found actually that these drugs work and we can cure over 80 percent of them. We had chemotherapy which is very important because let's say that patient and we should talk about relapsing in leukemia, let's say that person with APL relapses five six years later, I still have all the full chemotherapy armamentarium that control the disease which is incredible. So this is another example. Now unfortunately, APL is probably less than five percent of--or less of all AML. So it's not this works for all patients but for that particular subset, it works.
Lisa Garvin: In the nutshell, where do you see the future of AML treatment going?
Dr. Guillermo Garcia-Manero: The future is very clear and MD Anderson is putting a very significant effort on this under new leadership that is genomic data. For instance, we now know that patients with mutation of this gene called FLT-3, they have poor prognosis. But we also know that if we use FLT-3 inhibitors that these are drugs that target this particular gene, we can now do for remissions. Now we don't know yet what is the long term impact of this interventions but like any other tumor or any other field on oncology, it's combining all these different approaches and getting the genomic information so we can start not only prognostic in these patients differently through this genomic--and probably even, you know, epigenomic and proteomic, you know, all this basic science data. But that allows us not only to prognosticate but hopefully to identify new targets. We already have some. FLT-3 inhibitors, we have MEK inhibitors, et cetera. But the future actually is into the deep reading of the genomes of these patients and then the ability actually to take this to the clinic because it's okay if in some lab, in some big university, they sequence but it doesn't help, you know, patients soon so that comes to see me tomorrow. Soon, we're going to have that tool. And then I will be able and my colleagues are, you know, probably on their work to say, "Well, this person has this mutation or this constellation of mutations and this is the best drug or drugs that we can use." And that's the future is to break it in pieces and try to discover the different CMLs for AML. Probably AML has 15 CMLs, 15 molecular subtypes that one day will have some type of Gleevec like in APL example. And that will be the way to cure this disease but it's going to--and these efforts are already ongoing. It's going to require massive genomic annotations of lots of patients.
And this is what we call in layman's terms, personalized medicine, because it's personalized to that person's DNA.
Dr. Guillermo Garcia-Manero: Yes, but what the listeners need to understand that these--before we perform that personalization, if this is a word in English, I'm not sure, went to do the leg work. We need to do the foundation. And the foundation is, what we do in places like MD Anderson, is to read these samples so we can then correlate that information with outcomes, or with response to therapy, or hypothesize that whatever drug. And some these drugs, interestingly, they already been used for something else, for some of the disease but for some reason they may target that particular, that's the future. And that's why participation on these clinical trials is fundamental because you cannot go from--we'll going to sequence all these samples to come with treatment strategies. There's an intermediate step that is of course the sequencing but also understanding what this means. And we felt that step that is done in some type of coordinated control clinical research environment, we will never get there. And MD Anderson is putting massive resources to get this done.
Great, very enlightening. Thank you. If you have questions about anything you've heard today on Cancer Newsline, contact Ask MD Anderson at 1-877-mda-6789 or online at www.mdanderson.org/ask. [Background music] Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.
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