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Unraveling the Complexities of Sickle Cell Care

Dr. Johnson peels back the curtain on the unique challenges for pediatric patients with sickle cell disease, the risks involved with transitioning to adult care, and clinical trials and research that offer hope for a brighter future here and around the world.

Meet the speaker

Dr. Clarissa Johnson

Related information

About Sickle Cell Disease

Cook Children’s Hematology Program

Cook Children’s Hematology and Oncology Center

Cook Children’s Hematology and Oncology Clinical Research



Host: Hello and welcome to Cook Children’s Doc Talk. We're here today talking with Dr. Clarissa Johnson about sickle cell disease and the advanced treatments and research she leads here at Cook Children’s. Dr. Johnson is a member of Cook Children’s hematology and oncology team and the lead physician of the Sickle Cell program. She is actively involved in research Cook Children’s and has written extensively on the unique medical care needs an infection risks of children with sickle cell disease. In addition to her work at Cook Children’s Dr. Johnson has also made many medical mission trips to hospitals and clinics in Nigeria, Ethiopia and Eritrea. Those trips help to provide her with an even more intense drive to find a cure and she puts that drive into action every day in the compassionate care she provides to patients and families at Cook Children’s. Dr. Johnson, welcome and thank you for being here today.


Dr. Johnson: Thank you for having me.


Host: Can you start off by telling us a little about Cook Children's Sickle Cell Program?


Dr. Johnson: The program at Cook Children’s was established many years ago when the hematology oncology division was started at this institution by Dr. Paul Bowman. It has evolved over the years and by the time that I started working here in 2009 it was a well established program. I became the program director a short time after that and since that time have worked really to bring more research trials to our patient population and to have a cohesive management of care. Our team includes a nurse, a therapist. a social worker, and then three physicians who primarily take care of the patients here, of which I am one. We follow about four hundred patients from across the state of Texas, so that includes patients in West Texas, north of us in the Wichita Falls area, now Tyler in East Texas, south of us in Waco and then of course here in the immediate DFW area, which is probably where most of our patients come from.


Host: Can you tell us maybe a little bit about the types of advanced research trials we’re part of.


Dr. Johnson: Over the years Cook Children’s has been invited to participate in several trials, including trials on iron chelation in children, that is something that we use in children with sickle cell who need transfusion therapy and overtime may have iron levels build up in your body because of that, so we participate in that trial. We have collaborated with the group over in Dallas with some trials to look at the effect of something called a patent foramen ovale, or a small hole in the heart in terms of its influence on the risk of stroke in children with sickle cell disease. And in recent years we've been part of some therapeutic trials for various pharmacologic agents that have been developed trying to determine if there are medicines that will help us reduce the incidence of the most commonly seen complication in patients which is pain. So we have more recently done a trial looking at a drug that can be used in patient when patients are hospitalized to reduce the duration of their pain episodes and we are currently doing another trial of that nature.

And upcoming hopefully will be two other trials which are both outpatient, one looking at an oral medication that can be taken every day to try to increase the hemoglobin in patients with sickle cell disease, and that’s something called voxelotor, or GBT440. And another drug this called crizanlizumab which is also an outpatient drug which may also help reduce the frequency of pain crises that patients have when that drug is given once a month. So that's a trial that's not open here yet but we're looking forward to hopefully being able to participate in that when it is.


Host: According to the National Human Genome Research Institute, sickle cell disease is the most common inherited blood disorder in the U. S. particularly among African and Hispanic Americans. In fact, according to them, one in twelve African Americans and approximately one in one hundred Hispanic Americans carry the sickle cell trait. With so much prevalence why is it so challenging to find a cure?


Dr. Johnson: So. there is a cure for sickle cell disease which is stem cell transplantation. The limitation with that cure is that is not universally available to all patients. So we say is that we don't have a universal cure at this point. The other issue with stem cell transplant is that it requires you to have a donor. For most people a matched sibling is going to be the best donor but that presents challenges if both parents are carriers of a trait that causes the sickle cell disease, and therefore at risk every time they have a child to have another child with sickle cell disease. So that makes it challenging to encourage the parents to have more children with the idea of having a donor because for one there's only twenty five percent chance that that child will be a match for the affected child and they are also putting themselves at your twenty five percent risk to have another child with he disease. So that makes it a bit more challenging. Even parents who do have other children who are not affected that child needs to be a full sibling, so that's one limitation and again there is only a twenty five percent chance that even a full sibling is going to be a match. So that makes it difficult. We sometimes will do unrelated donor transplants because we can find people who can be a match for us even if they are not directly related to us but there are some more risk associated with doing that type of transplant as compared to a matched sibling transplant. So we typically reserve unrelated donor transplants for patients who are having the most severe complications in terms of determining what risk of transplant is acceptable to find a cure. So there are many limitations right now to what we have available to offer in terms of a cure for patients.


Host: It wasn't that long ago that babies born with sickle cell disease rarely lived past childhood, but thanks to continual advancements in treatments people with sickle cell disease are living well into their fifties. So can you talk a little about how treatment for sickle cell disease has changed over the past few years.


Dr. Johnson: There have been a lot of advancements in the treatment for sickle cell that has allow patients to live longer. Many many years ago patients were dying from infection when they were children and so one of the first real advancements was realizing that these children were having infections more frequently than other children their age and that by putting them on an antibiotic every day in early childhood that could reduce the risk for infection and therefore help them to live longer. Then, following that, vaccinations were developed that could also help prevent some of the infections that we worry about in sickle cell disease. The primary infection we worry about in young children with sickle cell disease is pneumococcal sepsis. And so that the bacteria called streptococcus pneumonia, which in the past it was probably the number one infection that was taking the lives of children with sickle cell disease. But with the development of penicillin, prophylaxis, and with vaccine prophylaxis, that has changed. So a lot fewer children are dying from that infection today. Children still develop that infection but I think with better treatment and knowing that they need to be evaluated quickly for fevers that has allowed us to reach them before that infection results in death.

So that was a major development. Other developments for children with sickle cell disease that has helped them to live longer include hydroxyurea. So that treatment was around for a while already treating cancers like leukemia but then it was noted that hydroxyurea tends to increase fetal hemoglobin and infants with sickle cell disease actually under the age of six months have fewer complications specifically related to the disease itself, and it was recognized that that was because their fetal hemoglobin levels are still very high, and the amount of sickle hemoglobin or sickle percentage in their blood was still low. That changes when they turn around the age of six months and then the fetal hemoglobin declines, so people start to look at what are ways we can try to maintain this high degree of fetal hemoglobin and can that protect kids from sickle cell disease from having complications. And they found that it could end so fart the best agent in terms of site of profile and response has been hydroxyurea. So there was a landmark trial in 1995 that look at use of hydroxyurea in adults with sickle cell disease and the study was actually terminated early because they found that people who were taking hydroxyurea as opposed to those who were not were having fewer hospitalizations, fewer transfusions, and less pain episodes. So that is a treatment that we now really propose for many of our patients especially those who have more severe disease or any of our patients who are looking for ways to try to reduce their frequency of pain episodes and hospitalizations.

Unfortunately, that treatment is not something that works for everyone, so some of our patients who have types of sickle cells such as the sickle C disease and something called sickle beta plus thalassemia may not tolerate that medication as well. So that is something to point out is that there are different types of sickle cell disease and they are not all exactly the same even though there are many features that can be very similar and so hydroxyurea so far has mainly been a treatment for those with more severe disease and so that leaves us with a limited option for those who may have less frequent complications but still have complications and cannot tolerate that medication.

So we're still looking and there's lots of interest now from pharmaceutical companies in sickle cell disease and so that's why we have these research trials that seem to constantly be popping up in the last couple of years to the point they were now having to decide which ones we can do and, so it's an exciting time in terms of research I think for sickle cell disease, but at the moment we still really just have the one drug that is truly effective.

I will mention l-glutamine or endari because a lot of families may have heard of that or people who are reading on the Internet about sickle cell disease, that is a recently FDA approved treatment for sickle cell disease aiming to reduce pain episodes but the only caveat I would say, is that the effects were not as dramatic as hydroxyurea so some families have been interested in trying that medication and we've been willing to do that but the trials were not as dramatic as the hydroxyurea trials and so I think many of us are still looking for other options you know in addition to hydroxyurea that can help our patients live lives that are less interrupted by complications of the disease.


Host: So, there are a lot of advanced treatments and research currently available what are the most promising treatments and clinical trials.


Dr. Johnson: So at the moment the ones that stand out the most to me would be the GBT-440 or voxelotor, which is a trial that we hope to open here soon. That drug is aimed at helping the red blood cell to hold oxygen better and that's a red blood cell that contains sickle hemoglobin. And in that way allowing that blood cell to have a longer survival than a cell with sickle hemoglobin been would ordinarily have, and also helping that red blood cell to carry oxygen better too and deliver it to the tissues of our body. So if that drug is effective then it can help patients to have less severe anemia and potentially less frequent pain episodes. That drug, so far, is being used either with hydroxyurea or without in the trials that are being done for it.


Host: And how severe, because you’ve mentioned pain episodes quite a bit, how severe can that pain be.


Dr. Johnson: So patients will describe a different ways. Some people will say it feels like someone is stabbing them with a knife, others will say it feels like there bone is being broken. Right now the mainstay of treatment that we have for addressing that acute pain and when a patient comes in with pain is opioid medication like a morphine or dilaudid. And so that may make some people feel a little bit hesitant or afraid when they hear that you're using that kind of medication for their child but unfortunately that’s how severe the pain can be. So we're hoping that with some of these treatments many will have less of a need for opioids.

I’m not sure yet that we have treatment that will completely eliminate the need to use them but maybe we won't need to use them as much. And I think a lot of families would hope for that too. They use the medications because that's what's available and they're really at this point is nothing else that's going to make their child's pain significantly better and we don't want kids to suffer, we don't want adults to suffer, so right now we use what we have to use. But I think it would be ideal to have other treatments that actually address what's happening from the disease itself in the body that would help with that pain more so than a pain medication. Because pain medications, really, I think of as just being a bandaid. They can't really reverse the underlying process. And sometimes we need a really strong bandaid, sometimes we may only need some ibuprofen, it all just depends. And everybody's pain experience is different so you know we have to remember that as well.


Host:: So currently the only known cure for sickle cell disease is transplantation which we talked about. But is a genetic cure on the horizon, and what is your involvement in that research here at Cook Children’s?


Dr. Johnson: So, there has been more interest since the human genome project several years ago at gene therapy for a lot of different diseases, and because we have known the genetic mutation that causes sickle cell for a long time, it is one of the diseases that has been proposed as a candidate for gene therapy. There have been trials already in a small number of patients and there are patients who have received gene therapy and who have effectively been cured from the disease.

So there are two methods. There is one of essentially trying to fix the gene of a sort, and there's one of basically inserting a correction next to the gene that helps the sickle gene to behave better. So those are very promising studies. Some patients as I said have already received that treatment and so far the outcomes have been good, we move with a little bit of trepidation when we start talking about manipulating genes because we always worry about the risk for inducing a cancer like leukemia and so that's why sometimes studies of that nature can move a little bit slowly but we have been approached by one of the companies that is involved in that type of therapy and as they move forward with trials we hope to be able to participate in that, and have told parents you know it's not something we're doing right now in these sorts of things move a little bit slowly just because of the nature of what's being done but hopefully that is something that will give hope to have a universal cure in the future because for that type of cure, it doesn't really matter what type of sickle cell disease you have, it is something that would be more readily available to more patients and it also doesn't require you to have a donor because in this instance you would be using your own cells, having them corrected by whatever gene editing or corrective process is being done and then having those cells given back into the body. So we're excited about that potential option in the future.


Host: Until we find a cure what are the greatest risk to kids with sickle cell disease and how can those risks be reduced or prevented.


Dr. Johnson: At the moment I think one of the greatest challenges is the transition, because we often see that as our patients transition from pediatric to adult care there can be a drop off in care for them. In many areas around the United States in particular, there are not adult sickle cell specialists available and so that role of care for those adult patients with sickle cell may fall on either a primary care doctor or maybe oncologists, which in some cases may be sufficient, but in other cases may not be, because the level of expertise may not be there to address some real challenges that can develop on people or adults with this disease. And so we see an increase in mortality in our patients in their early twenties between the ages of twenty and thirty, and we think that is closely linked to the problem of transition and having an adequate number of people with expertise to care for adults with sickle cell disease. It is one of the reasons that many years ago the age of transition changed here at Cook Children’s to the age of twenty one because we did not want to leave our patients in a vulnerable position of transitioning not only from high school to some type of career or college or training program, but in maybe also transitioning from the family home to being on their own, and then to add to that a transition of medical care and potentially having a drop off in care.

We feel that that was a real risk for our patients that could potentially result in mortality so that remains a very big challenge I think, and one of the biggest challenges that we face. I think we feel that we can manage most complications that may arise in our pediatric patients but we don't want to then help them have a full life through the age of twenty one and then have that drop off and that high risk for mortality. So around the country I think there have been efforts to try to figure out a different model for adults with sickle cell and how they can receive their care, and just encouraging more people who are doing the training of hematology oncology to consider being a sickle cell expert. We do have some luxury of having availability in Dallas for an adult sickle cell program and so that is where we refer most of our patients when they turn the age of twenty one, unless you're moving away from this area, but that still presents challenges, especially if you know based on geographics and where people live, it's still not the easiest and it may not, for some people, be the most ideal option.


Host: So one final question. Why is it so important to find a cure for sickle cell disease and why, beyond saving the lives of patients, does it matter.


Dr. Johnson: Well I don't know if people realize that sickle cell disease is really a global disease. So we only think of what we see in the United States. And the United States compared to the overall population is a small fraction of people maybe a hundred thousand people or so. But this is really a global disease that is all over the world. It affects people's ability to have a meaningful life and contribution to society if they are greatly affected by the disease and limited in their ability to reach their goals. We certainly see a lot of our patients, you know, strive to overcome that and certainly do very well with that, but it's a chronic illness. It’s a lifelong illness and it can also shorten the lifespan so I think when we ever we have a condition that causes so much medical burden for families and risks to not be able to live out your full potential because of a disease cutting that short, we always want to do whatever we can to help with that.

So I think it's very important to have more of a focus on this disease and I've been very pleased to see pharmaceutical companies and researchers starting to have more of a focus on this disease. And I think it's also very important for our families to get involved as well and trying to push that focus in trying to push legislatures and people who have the ability to improve funding for research to do so.


Host: If a family or someone in the medical industry listening to this wanted to get involved in making those changes, or giving a voice, how would they go about doing that?


Dr. Johnson: One good place to start would be the state legislature. Recently there are some committees that have been developed for looking at sickle cell disease and how it impacts the families and health care systems in Texas. So I think that's really one of the main places where change can be enacted. It's a little bit difficult for that to come strictly from a medical center because it's more of, at least referring to Texas, is more of a statewide issue. And so I think the more families sort of raise their voices and let legislators know that they have family members or friends who are affected by this disease and that they want to see more being offered for their family members and improvement in the cure really around the state, I think that's really a number one way to have change enacted. And I think we've seen that model with other diseases with some success.


Host: Dr. Johnson thank you for being here today and for sharing your extensive knowledge on the strides being made in the treatment of sickle cell disease for kids right here in Fort Worth as well as around the globe. And thank you for all you do here at Cook Children’s.


Dr. Johnson: Thank you for having me.


Host: We're so glad you could join us today. If you'd like to learn more about this program or any program at children's please visit us at Cook Children’s dot org.