Melanie Cole (Host): Welcome to Expert Insights with the Carle Foundation Hospital. I'm Melanie Cole. And today, we're discussing sickle cell disease. Joining me is Dr. Priyank Patel. He's a hematologist-oncologist at the Carle Foundation Hospital. Dr. Patel, it's a pleasure to have you join us today. Can you help us to recognize what sickle cell disease is, how it manifests in the body and the difference, if you would, between sickle cell trait and sickle cell disease?

Dr Priyank Patel: Thank you for having me on the podcast. So sickle cell disease is actually a genetic blood disorder. It is characterized by autosomal recessive inheritance pattern. The disorder happens because of a point mutation. There is one genetic code change in chromosome number 11 where the beta-globin gene is located. Amino acid valine is substituted to glutamine, which gives the whole problems after that.

The problem actually lies in the hemoglobin. Hemoglobin is a protein that is found in the red blood cells. It is necessary for binding oxygen to the lungs and carry oxygen to the tissues. Now, this abnormal hemoglobin that is formed as a result of this faulty gene mutation results in sickle cell disease.

Now, nature is quite fascinating how one simple mutation leads to lifelong consequences. Because of this mutation, the red blood cells, which are supposed to be flat biconcave discs, imagine like a donut with no holes in the center, turn into a sickle cell shape when there is a state of inflammation or low oxygen or any other stressors in the body. So not only they become sickle-shaped, but they also stick to each other, a term called polymerization, leading to decreased blood supply in the tiny, tiny capillaries in end-organs leading to chronic long-term damage and different manifestations of sickle cell disease.

Now, this disease is very common in the United States. Almost 100,000 Americans have sickle cell disease. There are more than a thousand infants born every year with sickle cell disease. And this is predominantly a disease that affects African-Americans. About one in 400 African Americans are affected by sickle cell disease. In reality, the bigger burden, which we have largely unspoken about, is basically in Africa, some parts of the middle east and Asia, where there are several fold more patients over there, but because of poor health care infrastructure over there, they are largely not managed in the proper manner.

Now, sickle cell disease is different than sickle cell trait. Disease is when we have one faulty gene that we acquire from a father and one faulty gene that we acquire from a mother. So when we have both of those genes, only then we manifest as sickle cell disease and all the complications of it.

Sickle cell trait is a condition in which we have acquired only one faulty gene, that means 50% of the production of hemoglobin is still going to be normal from a normal gene that we inherited from the other parent. In those cases, the disease manifestations are much modest or sometimes they are completely absent and people tend to have a much normal life.

Melanie Cole (Host): Well, thank you for that comprehensive answer, Dr. Patel. And it's so interesting to me that you said that with one faulty gene, it can affect the whole rest of this patient's life. Describe what life is like with sickle cell disease. What happens? What are some of the complications? Is this something that requires many doctor visits over many years? Tell us a little bit about what that's like.

Dr Priyank Patel: So unfortunately, somebody has sickle cell disease. They are going to require lifelong care. Now, patients with sickle cell disease are prone to many complications in virtually all the organ systems of the body. The most common of this complication that we see very frequently is vaso-occlusive crisis, basically restricted blood flow and blood supply through small blood vessels to the organs. This can cause chronic pain and sometimes acute exacerbations of pain that requires hospitalization, IV pain medications and things of that sort. The pain can be in joints in the back or any organ of the body.

Another complication, which is also associated with very high risk of death, is something that we call acute chest syndrome, which is manifested by inflammation and infiltration in the lungs from this sickle cell. Patients may require oxygen. They may require exchange transfusions in which we remove the blood and provide them healthier red blood cells from donors, a high risk of complications with that.

And the patients with sickle cell disease also tend to have low blood counts, which causes fatigue. Some patients require regular blood transfusions, which has its own set of complications with iatrogenic iron overload and complications of iatrogenic hemochromatosis. And because of the fact that the spleen eventually becomes dysfunctional in patients with sickle cell disease, as we know, spleen is a very important immune organ off of a body, so having a dysfunctional spleen also leads to increased risk of many severe infections. And most of these complications typically start in childhood. Patients can have strokes, heart problems, increased risk of blood clots, skin ulcers, so on and so forth. So if somebody has this problem, they are basically going to be in the healthcare system for their whole life.

Melanie Cole (Host): Well, then tell us about the sickle cell disease program at the Carle Foundation Hospital. What kind of support opportunities are available for patients and their families and the kind of care that they need, this comprehensive multidisciplinary care?

Dr Priyank Patel: So at Carle Foundation Hospital, we have a very robust hematology group. We do have a group of nine hematologists. We care about patients with sickle cell disease. We technically act as primary care doctors for sickle cell because all their disease manifestations from sickle cell basically revolve around their life. We work in conjunction with our orthopedic doctors, and other specialists to help take care of our patients. We also have pediatric hematology doctors who help us manage patients with sickle cell disease when they are less than 18 years old. We also partner with other institutions in larger cities for clinical trials and other newer types of treatments.

Melanie Cole (Host): Then why don't you share some of those newer types of treatments and some promising treatment developments that are down the line?

Dr Priyank Patel: Right. So sickle cell disease is a condition that is not curable so far, except in rare instances, when patients go for a bone marrow transplant, which has its own set of complications, not routinely done, and it's a very, very arduous process.

Hydroxyurea so far had been a drug that is the oldest and the first agent that had shown to decrease mortality and complications in these patients. This drug was extensively studied in late 1980s and early 1990s and was introduced in the market in 1998. Now, this is kind of the mainstay of treatment for sickle cell disease.

From 1998 until approximately 2016 or 2017, there were no new drugs. So there was a big hiatus. There were no new therapies at that time. Now, in the last few years, there have been some new agents. One of them is an amino acid called L-glutamine, which is a powder form that the patients take on a daily basis. This is a very highly purified powder form of L-glutamine, not something that is sold in the health food supplements aisle in the supermarket. This basically decreases the pain crisis. There is another drug called voxelotor, which is a hemoglobin polymerization inhibitor. Basically, it prevents the hemoglobin molecules, which have sickled to stick to each other. This in turn decreases the hemolysis or destruction of the red blood cells. This improves the hemoglobin counts. It improves the fatigue, decreases the pain episodes and hopefully decreases the transfusion dependency. And then there is another drug, which is a monoclonal antibody against P-selectin called crizanlizumab, which is given IV that reduces the pain episodes in these patients.

Now, these treatments are chronic and long-term and they require frequent and careful monitoring. The other new treatments that we have these days, which are not yet approved are gene therapies and gene editing techniques. This is not yet approved, but basically this involves using viral vectors to essentially repair the genetic defect, hoping for a normal red blood cell production or to increase the production of other hemoglobin types, such as hemoglobin F. These are still investigational. There are clinical trials at multiple centers around the country, and there are always ways to enroll patients in these trials.

Melanie Cole (Host): What an exciting time to be in your field, Dr. Patel. So what about genetic counseling for couples with one child with the disease that want to have another? Tell us a little bit about how you work with the families of a child with sickle cell disease.

Dr Priyank Patel: This is a big issue. We have genetic counselors at Carle who help our patients understand their options when they have a sickle cell trait or if they have sickle cell disease.

Melanie Cole (Host): As we get ready to wrap up, Dr. Patel, I'd like you to tell us about what's involved in the transition from pediatric to adult care for these patients and how patients with sickle cell disease can live a very productive life and what you're doing for them at the Carle Foundation Hospital?

Dr Priyank Patel: Transition from a pediatric physician to a adult hematologist is always difficult for these patients because they have really established themselves with this one doctor that they've been seeing since they are a little baby. And it's not only difficult for the patients, but also for their parents.

So number one thing as adult hematologists we have to do is to gain their trust. The other frequent problem that we see is many of our patients come from socioeconomic disadvantaged situations, and it is very important for us to enforce compliance and make sure that we are appropriately treating them and keeping them on board and giving them informed decision about all the treatment options.

To gain their trust is the most important thing. In my understanding, patients with sickle cell disease are often misunderstood, and we should find all ways to help them in all possible manner.

Melanie Cole (Host): Great episode. Thank you so much. Very informative, Dr. Patel. Thank you again for joining us. And for more information and to get connected with one of our providers, please visit carle.org. Or for a listing of Carle providers and to view Carle-sponsored educational activities, you can visit our website at carleconnect.com. That concludes this episode of Expert Insights with the Carle Foundation Hospital. I'm Melanie Cole. Thanks so much for listening