Selected Podcast
Sickle Cell Disease - Treatments, Advances and Cures
September is Childhood Cancer and Sickle Cell Awareness Month. In this episode of the Inside Pediatrics Podcast, Dr. Jeff Lebensburger shares an update on sickle cell disease – early detection and treatment, bone marrow transplants, current pain therapy and promising research for a cure within the first few months of life.
Featured Speaker:
Jeffrey Lebensburger, DO, MSPH
Jeffrey Lebensburger DO, MSPH, earned his undergraduate degree from the University of Pennsylvania, medical degree from Nova Southeastern College of Osteopathic Medicine and master’s degree in clinical and translational science from the University of Alabama at Birmingham (UAB) School of Public Health. Dr. Lebensburger is a board-certified pediatrician and pediatric hematologist-oncologist. He is director of the Pediatric Hematology Section in the UAB Division of Pediatric Hematology and Oncology. He has published more than 50 manuscripts and has received several prestigious grants from the National Institutes of Health (NIH), multiple societies and industries for research. On a national level, Dr. Lebensburger serves as an invited expert for the development of the American Society of Hematology (ASH) Sickle Cell Guidelines, FDA/ASH Sickle Cell Clinical Trial Endpoints, NIH Cure Sickle Cell Initiative and the ASH Sickle Cell Clinical Trials Network. Transcription:
Sickle Cell Disease - Treatments, Advances and Cures
Tiffany Kaczorowski (Host): Welcome to Inside Pediatrics, a podcast brought to you by Children’s Hospital of Alabama in Birmingham. I’m Tiffany Kaczorowski. September is Childhood Cancer and Sickle Cell Awareness month. And joining us today, is Dr. Jeffrey Lebensburger. He’s an Associate Professor at UAB, the University of Alabama at Birmingham. And is Director of the Hematology Section within the Division of Pediatric Hematology and Oncology here at Children’s. Welcome Dr. Lebensburger.
Jeffrey Lebensburger, DO, MSPH: Thank you for having me today.
Host: So, what is sickle cell disease? What does it actually do in the body?
Dr. Lebensburger: So, sickle cell disease impacts red blood cells. Our red blood cells carry oxygen throughout our body. In sickle cell disease, where the red cells change shape, they form a sickle cell shape or a moonlike shape. And as this goes through the body, this can cause complications such as pain, or organ damage.
Host: When do you typically diagnose a child with sickle cell? When do they start seeing symptoms?
Dr. Lebensburger: So, sickle cell is an inherited disease. So, we can find this out at birth. So, back in the 80s, we had a major problem where children with sickle cell disease and particularly young children would die from a certain type of infection. And some dedicated clinical researchers determined that if you give children penicillin at birth, you can prevent these life threatening infections. Because of this groundbreaking research, we were able to get sickle cell onto the newborn screen. So, everybody who has a child, when they are born, we will be able to determine whether their child has sickle cell disease.
Host: And do most people know, adults know when they are trying to get pregnant, when they are trying to have a child; that they have the disease, that they have a trait?
Dr. Lebensburger: So, unfortunately, many adults do not know their sickle cell trait status. And there are many dedicated researchers trying to improve trait education in the African American community.
Host: And what are some things that most people don’t know or realize about sickle cell disease?
Dr. Lebensburger: So, the hallmark symptom of sickle cell disease is a pain crisis. And many people feel that sickle cell and pain are the main complications. While pain is a major issue in our patients, we are also trying to get them to understand how sickle cell impacts their entire body. So, many patients with sickle cell disease while they suffer a lifetime of pain; the long term issues that they run into is problems with their organs. And so we have issues where people who have kidney problems, where they can no longer make their urine or breathing problems or heart problems. And so as both what they see everyday which is the concern for pain events but also the long term silent issues with sickle cell, is how can we better protect their organs.
Host: What is physically going on when they are experiencing that pain?
Dr. Lebensburger: The complication sickle cell is the sickle red blood cells, because they are not flexible, because they are stiff; can get stuck in a blood vessel. And the problem with that is all the areas past that can’t get any oxygen. So, whether it happens in the brain, that could lead to a stroke. Or you kidneys or heart could get damaged or what we commonly see is it can lead to pain event.
Host: How is COVID-19 affecting the sickle cell population or is it?
Dr. Lebensburger: COVID-19, we are just beginning to learn about. And so, one of the major issues with sickle cell patients is when they get a pneumonia, they can get very sick. So, it’s very important for our patients to be safe during this COVID time. But the things we still don’t know about is the long term damage and there are the concerns about whether this is going to cause long term lung or other complications. And so, really, we’re only beginning to understand how COVID is going to affect our sickle cell patient. So, we are really to all our patients, please stay safe, wear your mask and social distance.
Host: When we’re talking about the vulnerable parts of our population; kids and adults with sickle cell are in that category. And so, we’re wearing face masks, we’re distancing ourselves from people, not just to protect ourselves but to protect the vulnerable such as these kids and adults.
Dr. Lebensburger: Yes, that’s correct. And again, in a disease that the majority in Alabama are in African American communities; COVID in general, has tremendous impact on this community. So, again, we worry about both our patients and their family members because both of them are highly vulnerable populations.
Host: Now tell us about some of the treatments for sickle cell. Is there a cure for this disease?
Dr. Lebensburger: Yes. So, there’s both ways that we can reduce complications from sickle cell and there are ways to cure. And it’s been a very exciting few years in sickle cell because we’re developing new therapies and we’re testing them in clinical trials and we’re proving that they are safe and effective to give. The one with the most clinical data is a medicine called hydroxyurea. And the current recommendations is that all patients who are nine months of age and above, should be offered hydroxyurea. Because we know it can tremendously decrease complications and there is data also showing that it can improve people’s lives. And there’s also data showing that it increases patients’ lifespan.
Host: So, this originally started as a cancer drug. Do some patient families worry about that and how do you comfort them and let them know that it’s okay?
Dr. Lebensburger: Just like many medications are used for multiple reasons. Hydroxyurea has been in rare circumstances used as a cancer drug. But we now have over 40 years of safety data. And so, when we look at the rates of cancer among patients with sickle cell, who are on hydroxyurea and not on hydroxyurea; there is no difference in the rate of cancer. So, just like many medications that you hear of that are used for multiple reasons; hydroxyurea has been proven to be a very safe medication with its 40 year track record of safety.
Host: So, I hear that you in particular, when you are talking to your patients and patient families about hydroxyurea; that you show them under the microscope what it could look like. Can you describe how you talk to your patients about that particular drug?
Dr. Lebensburger: So, hydroxyurea works best when we get it at the highest dose that a patient can take. And so to do that, we really are focusing on staying on your medication. It’s really hard for children and adolescents to take a daily medicine. And so what we try to do is there’s multiple ways we try to improve adherence. Because the data clearly shows that those patients who take it a few days a week do not do as well as though patients who take it every day. So, we have multiple steps to try to improve people taking it every day.
And so what we think is exciting is that any patient with sickle cell, if they ever want to look at their blood smear, we can show it to them. And the great thing with hydroxyurea is we can show them the number of sickle cells they have when they started hydroxyurea all the way through to when they are on a very good dose, how they have very few sickle cells that we see in their blood smear.
Host: So, it changes the makeup of the blood cell?
Dr. Lebensburger: Hydroxyurea has many benefits. And one of them is to improve those red blood cells. So, the way they look is better. And we see a lot more of them. Because while it’s sickle cell anemia, meaning patients have low red blood cell numbers; when they are on hydroxyurea, we can get them back to more normal and so while they have sickle cell anemia; we can sometimes even correct their anemia portion of their disease.
Host: So, we are able to actually show them under the microscope what it looks like, what their blood looks like before and after taking that hydroxyurea for quite some time.
Dr. Lebensburger: Yeah and we encourage any of our patients if they ever want to look, to ask their doctor and we can go get them their blood smear so they can see it.
Host: And can show them proof of taking something every single day and how that will help them. Are there any other treatments for sickle cell disease that you’re recommending?
Dr. Lebensburger: So, in the last few years, research being done here at Children’s of Alabama and UAB have proven the safety and efficacy of other medicines. And so there are alternatives to hydroxyurea or what we have studied is in addition to hydroxyurea, we even see more dramatic benefit. So our goal for those who are not going to be cured of their disease is to offer as many options so that we can find the right sickle cell modifying treatment for each patient. So, there are new FDA approved medications. And so while hydroxyurea has 40 years of safety data, we now have five years of safety data on three additional medications.
Host: Okay, wonderful. But let’s talk about bone marrow transplant now.
Dr. Lebensburger: Yeah, so UAB and Children’s of Alabama have an excellent transplant team with Dr. Haines, and Dr. Goldman leading the way. And what they have, is they have the ability to cure patients who want to be cured from their sickle cell disease. So, things that we look at is whether or not you have a brother or a sister without sickle cell disease. Because if we have one and they are genetically matched; we have a 97% cure rate and that is a fantastic cure rate for sickle cell. If we do not have a brother or sister who is a match; we have alternative ways to be able to cure them as well. So, we ask anybody out there who wants to be cured of their disease to please come talk to us and to please learn more about bone marrow transplant options at Children’s of Alabama.
Host: Are there cases where bone marrow transplant is not an option, just given that type of sickle cell disease that they have?
Dr. Lebensburger: So, for patients who have a matched sibling, transplant is open to everybody. As we continue to show safety of bone marrow transplant using alternative methods; we’re going to be able to expand those options for more patients. But right now, as expected, first we start with those who have the most severe cases, we give them these alternative ways to be cured of their disease. With that safety, we can then continue to increase who is eligible for sickle cell transplant using these alternative approaches.
Host: And does that transplant last throughout their lives?
Dr. Lebensburger: Yeah. The great thing with sickle cell disease and curative therapies is we don’t have to completely correct their sickle cell. Because if sickle cell trait has very few complications, we don’t have to get them 100% corrected, we can just get them 50% corrected so that way, we can make them into sickle cell trait patients and those patients do very well just like the parents are doing today.
Host: Let’s talk about gene therapy now for sickle cell.
Dr. Lebensburger: So, not everybody has the ability to have a matched sibling donor, so a brother or a sister with the same genes or somebody who can be the transplant donor. So, now the technology exists where we can actually go in and correct the sickle cell gene itself. And so there’s different ways of doing it. we’re doing them here at UAB and there’s places throughout the country. And that will hopefully be the last treatment option we need out there because if we can take everybody’s cells, correct them and give them back; then we have developed an opportunity to cure every single patient, not just those who have a matched donor.
Host: So, that would be when the mother finds out that she carries the trait or that the family carries the trait, then you can know early on. How soon would you use that gene therapy in a child’s life?
Dr. Lebensburger: So, what we will do is we would have the ability to cure everybody starting at a very young age. Now the way that we do our clinical research or clinical trials is we always start with adults first and work our way down to the youngest children. So, we maybe sometime before we can give it to infants but that is our goal and so that every child born in America with sickle cell disease could be cured as soon as possible.
Host: How far out do you think that is?
Dr. Lebensburger: Right now, this amazing science is working in adults. And we are now bringing it to our pediatric patients here at Children’s of Alabama. And so, again, our goal is to be able to cure every child with sickle cell who wants to be cured. And so we do think it’s going to be in the near future that we will be able to offer this to any parent or any patient who wants this.
Host: That’s tremendous. That’s tremendous. One of the things that you are focused on right now is helping those sickle cell patients who are graduating from high school, transitioning over to adulthood. So, how important is that for them to be steadfast and to make sure that they transfer over and don’t lose sight of all of the care that they’ve been receiving?
Dr. Lebensburger: So, the great thing about Children’s of Alabama and the care that they’ve been receiving here from Dr. Hilliard and Dr. Howard, Dr. Bemrich-Stolz and others is that they love our hospital and they don’t want to leave. And it becomes a really difficult situation when they get to that point where they have to transition because it becomes a very scary situation. But what’s scary to doctors is we know that from 18 to 25 we do see a peak in how many patients are going to the emergency room. And we see a peak in patients who are passing away from sickle cell disease complications. And our concern is once they leave the pediatric side, they are not comfortable yet with the adult side and so they don’t go to their appointments, they don’t follow up with what they are supposed to until they get very sick and we can’t do anything about it.
So, we are really focusing on improving this process. So, it’s not just a transfer when they are 18 and out of high school. That transition really should start at 12 years of age and what we want to do is work for six years to make them comfortable with the process. And then we have great partners through the UAB Lifespan Comprehensive Sickle Cell Center. So, what happens is Dr. Joy Ogunsile and Dr. Julie Cantor who leads their program comes to Children’s of Alabama, sees them there, does their first visit or first two visits together with us. That way they are more comfortable to go across the street to UAB.
Host: So, they are not missing anything, you want to make sure that they continue with that same amount of care, continue to make their appointments and to see the doctors so they don’t end up in some sort of pain crisis or something even worse.
Dr. Lebensburger: Yeah, it is so important that continuation of care. And so, what we’re trying to do is get over that fear of the new provider by letting them see the doctors here first before they transition. But yeah, our patients need to be seen frequently and we really can’t get into the situation where our people are uncomfortable with new situations and therefore don’t seek care when they need to.
Host: And tell me about this grant that you recently received from the NIH, the National Institutes of Health that you are studying sickle cell patients and their kidneys, right?
Dr. Lebensburger: Yeah, so once complication of sickle cell patients is kidney disease. And as we talked about, pain is something that most people think about. But the kidneys are a very important organ and very vulnerable to sickle cell complications. What we know is about one quarter to on half of our patients with sickle cell disease are going to develop kidney disease. And unfortunately, some of these will go on to need dialysis which is something that is done when patients aren’t making urine properly. The problem with sickle cell disease is that one out of every four patients who start dialysis is going to pass away in the first year of starting dialysis. So, it is so vital that our patients stay on top of their kidney function and we are able to monitor this. Because what we have to do is we have to prevent people from progressing to chronic kidney disease because once we get there, our options are limited and our outcomes are dismal.
So, to do that, what our doctors do is we look at kidney function every year. The problem is, the way that we do this, it’s a very simple test. It’s a blood test. We do it on every clinic visit. But it doesn’t correlate well with kidney function in sickle cell patients. Because these tests they were made for patients who didn’t have sickle cell disease. So, what this grant is doing in both children and adults, is trying to develop a formula so that we can determine people’s kidney function that is made specifically for sickle cell patients not formulas that were made in non-sickle cell patients.
Host: So, how long is the study?
Dr. Lebensburger: So, this is a four year study. And what happens is a patient will go in, they will get their blood test, but these are just ways to estimate kidney function. What we’ll actually do though is we’ll offer any patient who wants to the ability to have a material injected in just like the same material that you use when you get a CT scan. And then what we do is we take blood every few hours for a total of four hours in pediatrics or six hours in adults and we monitor how quickly the kidneys get rid of this. And that’s how you actually measure kidney function. And so by doing both the gold standard test, by measuring kidney function and the lab test we do in our clinic, we can then develop the new formula. So, all patients would come once, they get the material that we give during a CT scan, have them stay in clinic for four to six hours and then one year later, they come back. And then with that information; we’ll be able to develop a sickle cell specific way to monitor people’s kidney’s function.
Host: Is this study open to other people across the state or across the region or is it really focused here at Children’s of Alabama and within the state of Alabama?
Dr. Lebensburger: So, the study is open for people who are five to 50 years of age. And we will have 200 pediatric patients and 200 adult patients. And when you do things like this, there is an opportunity for an issue where Alabama patients with sickle cell disease may be different than people who live in other areas. So, the way we’ve done this is it is a multicenter study. So, we will be doing this here in pediatrics and at St. Jude in Memphis in pediatrics and for the adult side, it will be at UAB, at University of Tennessee in Memphis and the University of Illinois Chicago. And what we did is we put together some of the top kidney sickle cell researchers so those in Chicago, those in Memphis and those who are here so we could really bring together a super team of sickle cell experts focused on kidney disease.
Host: Any other exciting news or studies that you guys are working on in the sickle cell world to give those patients hope?
Dr. Lebensburger: Another main focus of ours right now is helping pain events. So, while I said we need to improve awareness that sickle cell impacts other organs; the main thing that our children see now are pain events. And so we have the ability to give opioids and opioids are medication to provide analgesia or relief from pain. But there are lots of other things you can do. So, for example, we know that stress is a big part of pain. And if you are stressed during pain; it’s going to make that pain worse. So, we’re developing nonopioid strategies for pain as well. So, that way we can give them both opioids and nonopioid strategies. So, the Children’s of Alabama Sickle Cell Center has opened up a pain clinic. And through this pain clinic; we have the ability to give both of these at the same time. So, we gave virtual reality relaxation techniques where they put on a VR machine, it’s a nice deep breathing exercise for ten minutes and some of our patients even fall asleep despite being in a pain event after that. What we’ve shown is through this pain clinic, we can dramatically reduce hospitalization rates and we can actually get our patients home with less opioids than when you go to the emergency room.
So, our goal is to develop new strategies that can compliment opioids. Because many people think pain crisis is all about, I need my opioids. But there’s a lot of things that we need to do on top of that as well to try to reduce the complication from it.
Host: Tell us a little bit about the team approach and the team that takes care of these sickle cell patients here at Children’s.
Dr. Lebensburger: So yeah, it is so important to have a team. So, we want our family to have their own team of care and then their ability to come here and have their own family as well. So, we have excellent nurse practitioners here who have been taking care of sickle cell patients for a very long time. They are very dedicated to our patients and they are the first contact point for a lot of our patients. So, the nurse practitioners really play a major role in the care for our patients. But then what we also want to do is expand that to other services. We have a school liaison here who is fantastic. Unfortunately, with sickle cell, it can impact your ability to learn. And so it’s so important that our patients are seen by our school liaison. We get testing from a neuropsychologist to see what we can do to improve their school performance. So, we have that whole school system in place.
Some of our patients come from long distances or may not have the resources to get to Alabama. So, we have a social worker who is there dedicated to all of our patients. So, in addition to our nurse practitioners, our social workers, our school liaisons, our psychologists; we’ve developed a whole team so while doctors sometimes are the face of the program, it’s really these other people who really can deliver the excellent care to our patients.
Host: Sickle cell disease and your passion. Where did that come from?
Dr. Lebensburger: I think for anybody who does medicine, improving health disparities is a major goal of ours. And sickle cell disease is a disease that has significant healthcare disparities. We have limited providers who go into sickle cell and we have limited resources for sickle cell patients. And so, not only do we try to improve people’s lives with any disease but being able to do that in a group that already suffers from healthcare disparities was important for me.
Host: Let’s talk about some resources for parents, for caregivers and anyone else who wants to learn more about sickle cell disease. They could certainly go to our website that’s www.childrensal.org/sickle-cell-disease. Or www.hematology.org/scd. Any other thoughts from you Dr. Lebensburger?
Dr. Lebensburger: Educating patients and their families is so important about the disease. Because as doctors, we can tell people things but really having the patients learn about their own disease is so important. And that’s why we’ve redesigned the website and put a lot of educational content out there. So, we have both flyers that they can read. So, if they are in a pain event, they can download some of our materials and see what else they can do. If they are having trouble breathing, what they need to do. And we have those plus we also have videos where they can watch. So, they can show this to their friends, their families so people have a better understanding of sickle cell disease.
So, a very great thing that Children’s has done is supported our ability to improve parent and patient education on sickle cell disease. Now nationally, the American Society of Hematology has also placed an emphasis on sickle cell disease. So, they have a cure sickle cell initiative and they have sickle cell resources for patients as well. So, yes, it’s a big role of ours as providers, is improving the education of the parents and the families so they can make the best decisions on their own healthcare.
Host: Well thank you so much Dr. Lebensburger for joining us today.
Dr. Lebensburger: Thank you very much for allowing me to come and talk on this very important topic.
Host: Thanks for listening to Inside Pediatrics. More podcasts like this one can be found at www.childrensal.org/insidepediatrics.
Sickle Cell Disease - Treatments, Advances and Cures
Tiffany Kaczorowski (Host): Welcome to Inside Pediatrics, a podcast brought to you by Children’s Hospital of Alabama in Birmingham. I’m Tiffany Kaczorowski. September is Childhood Cancer and Sickle Cell Awareness month. And joining us today, is Dr. Jeffrey Lebensburger. He’s an Associate Professor at UAB, the University of Alabama at Birmingham. And is Director of the Hematology Section within the Division of Pediatric Hematology and Oncology here at Children’s. Welcome Dr. Lebensburger.
Jeffrey Lebensburger, DO, MSPH: Thank you for having me today.
Host: So, what is sickle cell disease? What does it actually do in the body?
Dr. Lebensburger: So, sickle cell disease impacts red blood cells. Our red blood cells carry oxygen throughout our body. In sickle cell disease, where the red cells change shape, they form a sickle cell shape or a moonlike shape. And as this goes through the body, this can cause complications such as pain, or organ damage.
Host: When do you typically diagnose a child with sickle cell? When do they start seeing symptoms?
Dr. Lebensburger: So, sickle cell is an inherited disease. So, we can find this out at birth. So, back in the 80s, we had a major problem where children with sickle cell disease and particularly young children would die from a certain type of infection. And some dedicated clinical researchers determined that if you give children penicillin at birth, you can prevent these life threatening infections. Because of this groundbreaking research, we were able to get sickle cell onto the newborn screen. So, everybody who has a child, when they are born, we will be able to determine whether their child has sickle cell disease.
Host: And do most people know, adults know when they are trying to get pregnant, when they are trying to have a child; that they have the disease, that they have a trait?
Dr. Lebensburger: So, unfortunately, many adults do not know their sickle cell trait status. And there are many dedicated researchers trying to improve trait education in the African American community.
Host: And what are some things that most people don’t know or realize about sickle cell disease?
Dr. Lebensburger: So, the hallmark symptom of sickle cell disease is a pain crisis. And many people feel that sickle cell and pain are the main complications. While pain is a major issue in our patients, we are also trying to get them to understand how sickle cell impacts their entire body. So, many patients with sickle cell disease while they suffer a lifetime of pain; the long term issues that they run into is problems with their organs. And so we have issues where people who have kidney problems, where they can no longer make their urine or breathing problems or heart problems. And so as both what they see everyday which is the concern for pain events but also the long term silent issues with sickle cell, is how can we better protect their organs.
Host: What is physically going on when they are experiencing that pain?
Dr. Lebensburger: The complication sickle cell is the sickle red blood cells, because they are not flexible, because they are stiff; can get stuck in a blood vessel. And the problem with that is all the areas past that can’t get any oxygen. So, whether it happens in the brain, that could lead to a stroke. Or you kidneys or heart could get damaged or what we commonly see is it can lead to pain event.
Host: How is COVID-19 affecting the sickle cell population or is it?
Dr. Lebensburger: COVID-19, we are just beginning to learn about. And so, one of the major issues with sickle cell patients is when they get a pneumonia, they can get very sick. So, it’s very important for our patients to be safe during this COVID time. But the things we still don’t know about is the long term damage and there are the concerns about whether this is going to cause long term lung or other complications. And so, really, we’re only beginning to understand how COVID is going to affect our sickle cell patient. So, we are really to all our patients, please stay safe, wear your mask and social distance.
Host: When we’re talking about the vulnerable parts of our population; kids and adults with sickle cell are in that category. And so, we’re wearing face masks, we’re distancing ourselves from people, not just to protect ourselves but to protect the vulnerable such as these kids and adults.
Dr. Lebensburger: Yes, that’s correct. And again, in a disease that the majority in Alabama are in African American communities; COVID in general, has tremendous impact on this community. So, again, we worry about both our patients and their family members because both of them are highly vulnerable populations.
Host: Now tell us about some of the treatments for sickle cell. Is there a cure for this disease?
Dr. Lebensburger: Yes. So, there’s both ways that we can reduce complications from sickle cell and there are ways to cure. And it’s been a very exciting few years in sickle cell because we’re developing new therapies and we’re testing them in clinical trials and we’re proving that they are safe and effective to give. The one with the most clinical data is a medicine called hydroxyurea. And the current recommendations is that all patients who are nine months of age and above, should be offered hydroxyurea. Because we know it can tremendously decrease complications and there is data also showing that it can improve people’s lives. And there’s also data showing that it increases patients’ lifespan.
Host: So, this originally started as a cancer drug. Do some patient families worry about that and how do you comfort them and let them know that it’s okay?
Dr. Lebensburger: Just like many medications are used for multiple reasons. Hydroxyurea has been in rare circumstances used as a cancer drug. But we now have over 40 years of safety data. And so, when we look at the rates of cancer among patients with sickle cell, who are on hydroxyurea and not on hydroxyurea; there is no difference in the rate of cancer. So, just like many medications that you hear of that are used for multiple reasons; hydroxyurea has been proven to be a very safe medication with its 40 year track record of safety.
Host: So, I hear that you in particular, when you are talking to your patients and patient families about hydroxyurea; that you show them under the microscope what it could look like. Can you describe how you talk to your patients about that particular drug?
Dr. Lebensburger: So, hydroxyurea works best when we get it at the highest dose that a patient can take. And so to do that, we really are focusing on staying on your medication. It’s really hard for children and adolescents to take a daily medicine. And so what we try to do is there’s multiple ways we try to improve adherence. Because the data clearly shows that those patients who take it a few days a week do not do as well as though patients who take it every day. So, we have multiple steps to try to improve people taking it every day.
And so what we think is exciting is that any patient with sickle cell, if they ever want to look at their blood smear, we can show it to them. And the great thing with hydroxyurea is we can show them the number of sickle cells they have when they started hydroxyurea all the way through to when they are on a very good dose, how they have very few sickle cells that we see in their blood smear.
Host: So, it changes the makeup of the blood cell?
Dr. Lebensburger: Hydroxyurea has many benefits. And one of them is to improve those red blood cells. So, the way they look is better. And we see a lot more of them. Because while it’s sickle cell anemia, meaning patients have low red blood cell numbers; when they are on hydroxyurea, we can get them back to more normal and so while they have sickle cell anemia; we can sometimes even correct their anemia portion of their disease.
Host: So, we are able to actually show them under the microscope what it looks like, what their blood looks like before and after taking that hydroxyurea for quite some time.
Dr. Lebensburger: Yeah and we encourage any of our patients if they ever want to look, to ask their doctor and we can go get them their blood smear so they can see it.
Host: And can show them proof of taking something every single day and how that will help them. Are there any other treatments for sickle cell disease that you’re recommending?
Dr. Lebensburger: So, in the last few years, research being done here at Children’s of Alabama and UAB have proven the safety and efficacy of other medicines. And so there are alternatives to hydroxyurea or what we have studied is in addition to hydroxyurea, we even see more dramatic benefit. So our goal for those who are not going to be cured of their disease is to offer as many options so that we can find the right sickle cell modifying treatment for each patient. So, there are new FDA approved medications. And so while hydroxyurea has 40 years of safety data, we now have five years of safety data on three additional medications.
Host: Okay, wonderful. But let’s talk about bone marrow transplant now.
Dr. Lebensburger: Yeah, so UAB and Children’s of Alabama have an excellent transplant team with Dr. Haines, and Dr. Goldman leading the way. And what they have, is they have the ability to cure patients who want to be cured from their sickle cell disease. So, things that we look at is whether or not you have a brother or a sister without sickle cell disease. Because if we have one and they are genetically matched; we have a 97% cure rate and that is a fantastic cure rate for sickle cell. If we do not have a brother or sister who is a match; we have alternative ways to be able to cure them as well. So, we ask anybody out there who wants to be cured of their disease to please come talk to us and to please learn more about bone marrow transplant options at Children’s of Alabama.
Host: Are there cases where bone marrow transplant is not an option, just given that type of sickle cell disease that they have?
Dr. Lebensburger: So, for patients who have a matched sibling, transplant is open to everybody. As we continue to show safety of bone marrow transplant using alternative methods; we’re going to be able to expand those options for more patients. But right now, as expected, first we start with those who have the most severe cases, we give them these alternative ways to be cured of their disease. With that safety, we can then continue to increase who is eligible for sickle cell transplant using these alternative approaches.
Host: And does that transplant last throughout their lives?
Dr. Lebensburger: Yeah. The great thing with sickle cell disease and curative therapies is we don’t have to completely correct their sickle cell. Because if sickle cell trait has very few complications, we don’t have to get them 100% corrected, we can just get them 50% corrected so that way, we can make them into sickle cell trait patients and those patients do very well just like the parents are doing today.
Host: Let’s talk about gene therapy now for sickle cell.
Dr. Lebensburger: So, not everybody has the ability to have a matched sibling donor, so a brother or a sister with the same genes or somebody who can be the transplant donor. So, now the technology exists where we can actually go in and correct the sickle cell gene itself. And so there’s different ways of doing it. we’re doing them here at UAB and there’s places throughout the country. And that will hopefully be the last treatment option we need out there because if we can take everybody’s cells, correct them and give them back; then we have developed an opportunity to cure every single patient, not just those who have a matched donor.
Host: So, that would be when the mother finds out that she carries the trait or that the family carries the trait, then you can know early on. How soon would you use that gene therapy in a child’s life?
Dr. Lebensburger: So, what we will do is we would have the ability to cure everybody starting at a very young age. Now the way that we do our clinical research or clinical trials is we always start with adults first and work our way down to the youngest children. So, we maybe sometime before we can give it to infants but that is our goal and so that every child born in America with sickle cell disease could be cured as soon as possible.
Host: How far out do you think that is?
Dr. Lebensburger: Right now, this amazing science is working in adults. And we are now bringing it to our pediatric patients here at Children’s of Alabama. And so, again, our goal is to be able to cure every child with sickle cell who wants to be cured. And so we do think it’s going to be in the near future that we will be able to offer this to any parent or any patient who wants this.
Host: That’s tremendous. That’s tremendous. One of the things that you are focused on right now is helping those sickle cell patients who are graduating from high school, transitioning over to adulthood. So, how important is that for them to be steadfast and to make sure that they transfer over and don’t lose sight of all of the care that they’ve been receiving?
Dr. Lebensburger: So, the great thing about Children’s of Alabama and the care that they’ve been receiving here from Dr. Hilliard and Dr. Howard, Dr. Bemrich-Stolz and others is that they love our hospital and they don’t want to leave. And it becomes a really difficult situation when they get to that point where they have to transition because it becomes a very scary situation. But what’s scary to doctors is we know that from 18 to 25 we do see a peak in how many patients are going to the emergency room. And we see a peak in patients who are passing away from sickle cell disease complications. And our concern is once they leave the pediatric side, they are not comfortable yet with the adult side and so they don’t go to their appointments, they don’t follow up with what they are supposed to until they get very sick and we can’t do anything about it.
So, we are really focusing on improving this process. So, it’s not just a transfer when they are 18 and out of high school. That transition really should start at 12 years of age and what we want to do is work for six years to make them comfortable with the process. And then we have great partners through the UAB Lifespan Comprehensive Sickle Cell Center. So, what happens is Dr. Joy Ogunsile and Dr. Julie Cantor who leads their program comes to Children’s of Alabama, sees them there, does their first visit or first two visits together with us. That way they are more comfortable to go across the street to UAB.
Host: So, they are not missing anything, you want to make sure that they continue with that same amount of care, continue to make their appointments and to see the doctors so they don’t end up in some sort of pain crisis or something even worse.
Dr. Lebensburger: Yeah, it is so important that continuation of care. And so, what we’re trying to do is get over that fear of the new provider by letting them see the doctors here first before they transition. But yeah, our patients need to be seen frequently and we really can’t get into the situation where our people are uncomfortable with new situations and therefore don’t seek care when they need to.
Host: And tell me about this grant that you recently received from the NIH, the National Institutes of Health that you are studying sickle cell patients and their kidneys, right?
Dr. Lebensburger: Yeah, so once complication of sickle cell patients is kidney disease. And as we talked about, pain is something that most people think about. But the kidneys are a very important organ and very vulnerable to sickle cell complications. What we know is about one quarter to on half of our patients with sickle cell disease are going to develop kidney disease. And unfortunately, some of these will go on to need dialysis which is something that is done when patients aren’t making urine properly. The problem with sickle cell disease is that one out of every four patients who start dialysis is going to pass away in the first year of starting dialysis. So, it is so vital that our patients stay on top of their kidney function and we are able to monitor this. Because what we have to do is we have to prevent people from progressing to chronic kidney disease because once we get there, our options are limited and our outcomes are dismal.
So, to do that, what our doctors do is we look at kidney function every year. The problem is, the way that we do this, it’s a very simple test. It’s a blood test. We do it on every clinic visit. But it doesn’t correlate well with kidney function in sickle cell patients. Because these tests they were made for patients who didn’t have sickle cell disease. So, what this grant is doing in both children and adults, is trying to develop a formula so that we can determine people’s kidney function that is made specifically for sickle cell patients not formulas that were made in non-sickle cell patients.
Host: So, how long is the study?
Dr. Lebensburger: So, this is a four year study. And what happens is a patient will go in, they will get their blood test, but these are just ways to estimate kidney function. What we’ll actually do though is we’ll offer any patient who wants to the ability to have a material injected in just like the same material that you use when you get a CT scan. And then what we do is we take blood every few hours for a total of four hours in pediatrics or six hours in adults and we monitor how quickly the kidneys get rid of this. And that’s how you actually measure kidney function. And so by doing both the gold standard test, by measuring kidney function and the lab test we do in our clinic, we can then develop the new formula. So, all patients would come once, they get the material that we give during a CT scan, have them stay in clinic for four to six hours and then one year later, they come back. And then with that information; we’ll be able to develop a sickle cell specific way to monitor people’s kidney’s function.
Host: Is this study open to other people across the state or across the region or is it really focused here at Children’s of Alabama and within the state of Alabama?
Dr. Lebensburger: So, the study is open for people who are five to 50 years of age. And we will have 200 pediatric patients and 200 adult patients. And when you do things like this, there is an opportunity for an issue where Alabama patients with sickle cell disease may be different than people who live in other areas. So, the way we’ve done this is it is a multicenter study. So, we will be doing this here in pediatrics and at St. Jude in Memphis in pediatrics and for the adult side, it will be at UAB, at University of Tennessee in Memphis and the University of Illinois Chicago. And what we did is we put together some of the top kidney sickle cell researchers so those in Chicago, those in Memphis and those who are here so we could really bring together a super team of sickle cell experts focused on kidney disease.
Host: Any other exciting news or studies that you guys are working on in the sickle cell world to give those patients hope?
Dr. Lebensburger: Another main focus of ours right now is helping pain events. So, while I said we need to improve awareness that sickle cell impacts other organs; the main thing that our children see now are pain events. And so we have the ability to give opioids and opioids are medication to provide analgesia or relief from pain. But there are lots of other things you can do. So, for example, we know that stress is a big part of pain. And if you are stressed during pain; it’s going to make that pain worse. So, we’re developing nonopioid strategies for pain as well. So, that way we can give them both opioids and nonopioid strategies. So, the Children’s of Alabama Sickle Cell Center has opened up a pain clinic. And through this pain clinic; we have the ability to give both of these at the same time. So, we gave virtual reality relaxation techniques where they put on a VR machine, it’s a nice deep breathing exercise for ten minutes and some of our patients even fall asleep despite being in a pain event after that. What we’ve shown is through this pain clinic, we can dramatically reduce hospitalization rates and we can actually get our patients home with less opioids than when you go to the emergency room.
So, our goal is to develop new strategies that can compliment opioids. Because many people think pain crisis is all about, I need my opioids. But there’s a lot of things that we need to do on top of that as well to try to reduce the complication from it.
Host: Tell us a little bit about the team approach and the team that takes care of these sickle cell patients here at Children’s.
Dr. Lebensburger: So yeah, it is so important to have a team. So, we want our family to have their own team of care and then their ability to come here and have their own family as well. So, we have excellent nurse practitioners here who have been taking care of sickle cell patients for a very long time. They are very dedicated to our patients and they are the first contact point for a lot of our patients. So, the nurse practitioners really play a major role in the care for our patients. But then what we also want to do is expand that to other services. We have a school liaison here who is fantastic. Unfortunately, with sickle cell, it can impact your ability to learn. And so it’s so important that our patients are seen by our school liaison. We get testing from a neuropsychologist to see what we can do to improve their school performance. So, we have that whole school system in place.
Some of our patients come from long distances or may not have the resources to get to Alabama. So, we have a social worker who is there dedicated to all of our patients. So, in addition to our nurse practitioners, our social workers, our school liaisons, our psychologists; we’ve developed a whole team so while doctors sometimes are the face of the program, it’s really these other people who really can deliver the excellent care to our patients.
Host: Sickle cell disease and your passion. Where did that come from?
Dr. Lebensburger: I think for anybody who does medicine, improving health disparities is a major goal of ours. And sickle cell disease is a disease that has significant healthcare disparities. We have limited providers who go into sickle cell and we have limited resources for sickle cell patients. And so, not only do we try to improve people’s lives with any disease but being able to do that in a group that already suffers from healthcare disparities was important for me.
Host: Let’s talk about some resources for parents, for caregivers and anyone else who wants to learn more about sickle cell disease. They could certainly go to our website that’s www.childrensal.org/sickle-cell-disease. Or www.hematology.org/scd. Any other thoughts from you Dr. Lebensburger?
Dr. Lebensburger: Educating patients and their families is so important about the disease. Because as doctors, we can tell people things but really having the patients learn about their own disease is so important. And that’s why we’ve redesigned the website and put a lot of educational content out there. So, we have both flyers that they can read. So, if they are in a pain event, they can download some of our materials and see what else they can do. If they are having trouble breathing, what they need to do. And we have those plus we also have videos where they can watch. So, they can show this to their friends, their families so people have a better understanding of sickle cell disease.
So, a very great thing that Children’s has done is supported our ability to improve parent and patient education on sickle cell disease. Now nationally, the American Society of Hematology has also placed an emphasis on sickle cell disease. So, they have a cure sickle cell initiative and they have sickle cell resources for patients as well. So, yes, it’s a big role of ours as providers, is improving the education of the parents and the families so they can make the best decisions on their own healthcare.
Host: Well thank you so much Dr. Lebensburger for joining us today.
Dr. Lebensburger: Thank you very much for allowing me to come and talk on this very important topic.
Host: Thanks for listening to Inside Pediatrics. More podcasts like this one can be found at www.childrensal.org/insidepediatrics.