The incidence of acute lymphoblastic leukemia is approximately 15 percent higher in Hispanics than Caucasians and the overall survival rate is lower in this population.
But little is known about why.
Are genetic variations the cause of the differences in survival rates?
Are there variations even within the populations classified as Hispanic?
Dr. Terrie Flatt is here today to discuss leading research in conjunction with a partner hospital in Mexico to better understand the role of ethnicity in acute lymphoblastic leukemia (ALL) and how patients with certain cytogenetic arrangements in their cancer cells may respond to treatment.
Understanding the Role of Genetic Variations in Hispanic Pediatric Cancer Patients
Featured Speaker:
Learn more about Dr. Flatt
Terrie Flatt, MD
Dr. Flatt is a pediatric hematologist/oncologist and is director of the Hematologia Oncologia Puente de Esperanze clinic (Hematology Oncology Bride of Hope) at Children’s Mercy Kansas City. Dr. Flatt received his medical degree from the University of North Texas Health Science Center. He completed a residency in general pediatrics at Driscoll Children’s Hospital and a fellowship in hematology/oncology at Children’s Mercy. Dr. Flatt is fluent and medically trained in Spanish, and has a master’s degree in Latin American Studies, Anthropology and an undergraduate degree in Spanish Political Science.Learn more about Dr. Flatt
Transcription:
Understanding the Role of Genetic Variations in Hispanic Pediatric Cancer Patients
Dr. Michael Smith (Host): Welcome to Transformational Pediatrics. I am Dr. Michael Smith and our topic is understanding the role of genetic variations in Hispanic pediatric cancer patients. My guest is Dr. Terry Flatt. Dr. Flatt is a pediatric hematologist and oncologist and is Director of the Hematology/Oncology Bride of Hope at Children’s Mercy Kansas City. Dr. Flatt, welcome to the show.
Dr. Terry Flatt (Guest): Thank you.
Dr. Smith: So, let’s just start off. Describe for us the difference in pediatric cancer outcomes between Hispanic and Caucasian patients.
Dr. Flatt: Sure. I think the first place that we would want to start is with acute lymphoblastic leukemia, which is the most common childhood cancer for all populations. You know, we, among Caucasians, we’ve actually reached a very, very nice survival rate approaching approximately 90% survival rates with standard risk acute lymphoblastic leukemia. Hispanics, on the other hand, are reaching somewhere between 78 and, on the high end 85%, survival rate. So, that’s one disease in particular because it is so common. It is the most common childhood cancer and, also, if you factor in that Hispanics have a 15% higher incidence of acute lymphoblastic leukemia, this difference in survival rate has to be addressed. That’s one of the major differences is the event-free survival, meaning the fact that they relapse more frequently and they die from this disease more frequently compared to Caucasians. The other aspect that I would mention is that if you look at some solid tumors among Hispanic patients, they will often present with more advanced disease meaning larger tumors. For example, Ewing’s Sarcoma, which is one of the most common bone and soft tissue cancers, they often present with much larger tumors, often with metastatic disease. Hence, because of that, they will have a poorer outcome.
Dr. Smith: Before we get into some of the theories of why we see this difference, why is this issue so important to you personally, Dr. Flatt?
Dr. Flatt: I was actually an anthropologist before I went to medical school. I taught at university and worked at various parts of Latin America, but, specifically, spent the vast majority of my time in Mexico with indigenous people and just really living. I mean, that’s what anthropology is about. It’s about living and learning how other people view the world. I was very young when I was doing that and I think, you know, for me it was such a life-changing experience. I was with some of the most wonderful, generous, compassionate people that I’ve ever been with. I would venture to say that those folks really changed my life and they changed my perspective of the world. When I finally made this decision to go into the medical field and, in particular, pediatric oncology I knew that that was the population that I would dedicate the rest of my life to. So, for me, this is really about trying to give back something that was so generously given to me when I was much, much younger and had a lot to learn.
Dr. Smith: That’s nice.
Dr. Flatt: That’s really it. I mean, it has to do with a real passion for that population.
Dr. Smith: Nice story, Dr. Flatt. Nice story. Let’s go back then. So, we have this difference between Hispanic and Caucasian patients when it comes to cancers and, specifically, the pediatric cancers. What are the different theories and what’s the leading theory on why the outcomes are so different?
Dr. Flatt: Well, I think what we are starting to understand about acute lymphoblastic leukemia is that as we unravel more and more of the mysteries of the cytogenetics of these leukemia cells, what we are slowly--and I say slowly because it’s taken us a lot of time to come to this--I think what we are discovering is that Hispanics have a higher incidence of what we would call “poor prognostic features”. Some of these features are genetic that we are just on the tip of the iceberg in terms of learning about. Just as a very small example, there’s one that’s called “cytokine receptor-like factor 2” and that has to do essentially with turning on an off stem cells and the progression to cancer. What we know is that Hispanics have a higher incidence of this particular mutation. Again, this is very, very cutting edge. This is new material and it’s important because with that particular mutation, there is a potential that it could have targeted drug action and that’s what makes it so incredibly important as we go forward. So, I think much of it is cytogenetic and I think some of that may well be determined by a person’s ethnicity. If you look at a Mexican, I mean, yes, part of their inheritance is going to be from the Spanish, right? From the Spanish colonial era.
Dr. Smith: Right.
Dr. Flatt: And in much of it is going to be from the indigenous piece, right? Be it descendants from the Aztecs, decedents of the Mayans, descendants of the Tlaxcaltecs. I mean, there are many, many tribes of indigenous people in Mexico. So, I think maybe these differences are driven by that. By the same token, how they metabolize drugs. I mean, we have personalized medicine. We know individuals can metabolize chemotherapy and drugs differently, so I suspect that that would be the case based on ethnicity.
Dr. Smith: What’s been done recently to maybe better understand the issue? What’s some of the research that’s going on right now to address the difference in outcome?
Dr. Flatt: Well, I will tell you, I think to a very large degree in terms of looking at this from a racial point of view, from an ethnicity point of view, there has not been a tremendous amount that has been done to date. A lot of this is going back retrospectively and then looking at different cytogenetic markers. I think, more than anything, the fact that every day we take this to the edge in terms of trying to understand the cytogenetics and then piece that back to, for example, in this particular case that I’m interested in, ethnicity and racial groups. So, I think we are on the verge of making some big finds in this but it’s very new in terms of looking at this based on ethnicity and race.
Dr. Smith: What about some of the research you’re doing specifically at Children’s Mercy?
Dr. Flatt: What I’m really trying to do and, I mean, Children’s Mercy, thank goodness, supports this and our division supports it; I’m really trying to reach out to other centers across Mexico and obtain samples right from Mexico where you truly will get the real mix of the person who may be 20% Spaniard meaning--what I mean by that is there’s Spanish ancestry--and they may be 80%, for example, what we would say here in the United States Aztec.
Dr. Smith: Okay.
Dr. Flatt: We are all familiar with the Aztecs. What does that mean to their outcome? One of the first steps in this research, we are at this place now in science where we can look at a person’s ethnic racial makeup and they would be able to tell me the percentages: how much African, how much Asian, how much Native American. What I mean by that is Mesoamerican, meaning pre-Columbian blood and European. Then, I’m correlating that to cytogenetics and, of course, through that by having that piece of ethnic information, racial information, we are actually able to look at polymorphisms that are specific to populations. So, that’s what we are doing right now, specifically.
Dr. Smith: Dr. Flatt, I want to thank you for the work that you’re doing at Children’s Mercy and I want to thank you for coming on the show. You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Michael Smith. Have a great day.
Understanding the Role of Genetic Variations in Hispanic Pediatric Cancer Patients
Dr. Michael Smith (Host): Welcome to Transformational Pediatrics. I am Dr. Michael Smith and our topic is understanding the role of genetic variations in Hispanic pediatric cancer patients. My guest is Dr. Terry Flatt. Dr. Flatt is a pediatric hematologist and oncologist and is Director of the Hematology/Oncology Bride of Hope at Children’s Mercy Kansas City. Dr. Flatt, welcome to the show.
Dr. Terry Flatt (Guest): Thank you.
Dr. Smith: So, let’s just start off. Describe for us the difference in pediatric cancer outcomes between Hispanic and Caucasian patients.
Dr. Flatt: Sure. I think the first place that we would want to start is with acute lymphoblastic leukemia, which is the most common childhood cancer for all populations. You know, we, among Caucasians, we’ve actually reached a very, very nice survival rate approaching approximately 90% survival rates with standard risk acute lymphoblastic leukemia. Hispanics, on the other hand, are reaching somewhere between 78 and, on the high end 85%, survival rate. So, that’s one disease in particular because it is so common. It is the most common childhood cancer and, also, if you factor in that Hispanics have a 15% higher incidence of acute lymphoblastic leukemia, this difference in survival rate has to be addressed. That’s one of the major differences is the event-free survival, meaning the fact that they relapse more frequently and they die from this disease more frequently compared to Caucasians. The other aspect that I would mention is that if you look at some solid tumors among Hispanic patients, they will often present with more advanced disease meaning larger tumors. For example, Ewing’s Sarcoma, which is one of the most common bone and soft tissue cancers, they often present with much larger tumors, often with metastatic disease. Hence, because of that, they will have a poorer outcome.
Dr. Smith: Before we get into some of the theories of why we see this difference, why is this issue so important to you personally, Dr. Flatt?
Dr. Flatt: I was actually an anthropologist before I went to medical school. I taught at university and worked at various parts of Latin America, but, specifically, spent the vast majority of my time in Mexico with indigenous people and just really living. I mean, that’s what anthropology is about. It’s about living and learning how other people view the world. I was very young when I was doing that and I think, you know, for me it was such a life-changing experience. I was with some of the most wonderful, generous, compassionate people that I’ve ever been with. I would venture to say that those folks really changed my life and they changed my perspective of the world. When I finally made this decision to go into the medical field and, in particular, pediatric oncology I knew that that was the population that I would dedicate the rest of my life to. So, for me, this is really about trying to give back something that was so generously given to me when I was much, much younger and had a lot to learn.
Dr. Smith: That’s nice.
Dr. Flatt: That’s really it. I mean, it has to do with a real passion for that population.
Dr. Smith: Nice story, Dr. Flatt. Nice story. Let’s go back then. So, we have this difference between Hispanic and Caucasian patients when it comes to cancers and, specifically, the pediatric cancers. What are the different theories and what’s the leading theory on why the outcomes are so different?
Dr. Flatt: Well, I think what we are starting to understand about acute lymphoblastic leukemia is that as we unravel more and more of the mysteries of the cytogenetics of these leukemia cells, what we are slowly--and I say slowly because it’s taken us a lot of time to come to this--I think what we are discovering is that Hispanics have a higher incidence of what we would call “poor prognostic features”. Some of these features are genetic that we are just on the tip of the iceberg in terms of learning about. Just as a very small example, there’s one that’s called “cytokine receptor-like factor 2” and that has to do essentially with turning on an off stem cells and the progression to cancer. What we know is that Hispanics have a higher incidence of this particular mutation. Again, this is very, very cutting edge. This is new material and it’s important because with that particular mutation, there is a potential that it could have targeted drug action and that’s what makes it so incredibly important as we go forward. So, I think much of it is cytogenetic and I think some of that may well be determined by a person’s ethnicity. If you look at a Mexican, I mean, yes, part of their inheritance is going to be from the Spanish, right? From the Spanish colonial era.
Dr. Smith: Right.
Dr. Flatt: And in much of it is going to be from the indigenous piece, right? Be it descendants from the Aztecs, decedents of the Mayans, descendants of the Tlaxcaltecs. I mean, there are many, many tribes of indigenous people in Mexico. So, I think maybe these differences are driven by that. By the same token, how they metabolize drugs. I mean, we have personalized medicine. We know individuals can metabolize chemotherapy and drugs differently, so I suspect that that would be the case based on ethnicity.
Dr. Smith: What’s been done recently to maybe better understand the issue? What’s some of the research that’s going on right now to address the difference in outcome?
Dr. Flatt: Well, I will tell you, I think to a very large degree in terms of looking at this from a racial point of view, from an ethnicity point of view, there has not been a tremendous amount that has been done to date. A lot of this is going back retrospectively and then looking at different cytogenetic markers. I think, more than anything, the fact that every day we take this to the edge in terms of trying to understand the cytogenetics and then piece that back to, for example, in this particular case that I’m interested in, ethnicity and racial groups. So, I think we are on the verge of making some big finds in this but it’s very new in terms of looking at this based on ethnicity and race.
Dr. Smith: What about some of the research you’re doing specifically at Children’s Mercy?
Dr. Flatt: What I’m really trying to do and, I mean, Children’s Mercy, thank goodness, supports this and our division supports it; I’m really trying to reach out to other centers across Mexico and obtain samples right from Mexico where you truly will get the real mix of the person who may be 20% Spaniard meaning--what I mean by that is there’s Spanish ancestry--and they may be 80%, for example, what we would say here in the United States Aztec.
Dr. Smith: Okay.
Dr. Flatt: We are all familiar with the Aztecs. What does that mean to their outcome? One of the first steps in this research, we are at this place now in science where we can look at a person’s ethnic racial makeup and they would be able to tell me the percentages: how much African, how much Asian, how much Native American. What I mean by that is Mesoamerican, meaning pre-Columbian blood and European. Then, I’m correlating that to cytogenetics and, of course, through that by having that piece of ethnic information, racial information, we are actually able to look at polymorphisms that are specific to populations. So, that’s what we are doing right now, specifically.
Dr. Smith: Dr. Flatt, I want to thank you for the work that you’re doing at Children’s Mercy and I want to thank you for coming on the show. You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Michael Smith. Have a great day.