“Traditionally, treatment for sickle cell disease has been palliative, and there have not been a lot of options to prevent long term complications,” said Dr. Alex George, assistant professor of pediatrics – hematology at Baylor College of Medicine and a physician with the sickle cell program at Texas Children’s Hematology Center. “But we are starting to see new treatments that are focused on long-term maintenance, rather than just addressing acute crises.”
Sickle cell disease is an inherited disorder in which red blood cells are irregularly shaped. These sickle-shaped cells can get stuck in small blood vessels, which can slow or block blood flow and oxygen to parts of the body, resulting in painful episodes, serious infections, chronic anemia and damage to body organs.
As recently as the 1980s, U.S. children were dying of infection before they were even diagnosed and received treatment for the disease. A large-scale trial that proved the effectiveness of penicillin for infections in infants and children, coupled with universal screening for all newborns in the United States dramatically improved the life expectancy of sickle cell patients.
Despite those improvements, treatment did not continue to advance significantly. For many years patients have had two primary treatment options:
Chronic blood transfusions
Once-a-month transfusions replenish the body with non-sickle cell blood; however, the procedures are time intensive and expensive and are reserved for sickle cell patients at high risk of stroke due to poor blood flow.
Originally developed as a chemotherapy drug, this treatment is designed to turn back on the fetal hemoglobin that is present at birth and is replaced by adult hemoglobin by about age 1, with the goal of reducing the amount of sickle cells in the blood. Initially used only in adults, this treatment is now being used in children as well.
In addition to those two treatments, patients who are experiencing pain crises are treated in the hospital with intravenous pain medication.
Current research and ongoing clinical trials show promise for improved treatment options. George offered an overview of some of the work going on at Texas Children’s Hematology Center.
This study is looking into whether transfusion patients can be switched to hydroxyurea as a maintenance form of therapy. It’s a national trial that is being conducted at Texas Children’s Hematology Center and other sites nationally.
About 5 to 10 percent of sickle cell patients are at high risk for strokes, which is determined through ultrasounds of blood flow to the brain. This segment of patients is put on a monthly transfusion regiment; however the risks of this over time include iron overload and the development of antibodies that work against the new blood, making transfusions less effective.
“This is a very exciting trial because it’s a more efficient form of therapy. We’re hopeful that this will provide a new option for patients currently on transfusion,” George said.
Pain crisis trial
This large-scale trial that includes Texas Children’s Hematology Center is investigating a novel way of treating pain crises by targeting the underlying cause of the crises instead of focusing only on pain palliation. It involves a drug called MAST-188 that could potentially disrupt the log-jam of sickle red blood cells in the blood vessels.
This study will examine the use of a molecular approach that could potentially serve as a long-term form of therapy to reduce the severity of sickle cell disease. It involves a monthly infusion of an antibody that blocks molecules called P-selectin that line the blood vessels. P-selectin causes cells to stick together and impair blood flow.
Hydroxyurea dose prediction trial
A trial studying another way of using hydroxyurea also offers hope for more efficient treatment, George said. Currently, patients start on a low dose of this drug and step up over time.
It’s been shown that a higher dose is more effective, however too high a dose can cause bone marrow suppression, George explained. There’s no way to predict the maximum dose for individual patients, so dosages are stepped up over about six months to one year to find the ideal dose. It’s a cumbersome, time consuming process, he said.
This trial is examining the safety and effectiveness of predicting the ideal dose through an equation that’s been developed that includes height, weight, kidney function and blood count.
“We are essentially trying to find a better way of using a known medication, with the goal of simplifying the use of the drug to find the ideal dose long-term,” he said.
If researchers and clinicians can establish that it works in the United States, this treatment can be adapted for use in Africa, where the Texas Children’s Hematology Center, Texas Children’s Global Health Initiative, Baylor College of Medicine International Pediatric AIDS Initiative and Baylor College of Medicine’s Department of Pediatrics has launched a sickle cell screening program in Angola in partnership with the Chevron Corporation and will continue to expand its efforts to improve screening and treatment for the disease in other parts of Africa.
The establishment of the sickle cell program in Africa also offers the opportunity to potentially enroll many more patients in clinical trials, which could positively impact the current state of research, George said.
Sickle cell disease historically arose in Africa, where today it is estimated that up to 2 percent of newborns have sickle cell disease. Sickle cell disease is also common in parts of India and the Middle East and is now a global health problem. In the United States, it is most common in African-Americans, with one in 500 African-American infants born with sickle cell disease. Of note, however, people of all ethnicities can be affected by this condition.
The sickle cell program at Texas Children’s Hematology Center is one of the largest in the country, with about 1,000 patients being actively followed. Physicians, nurses and social workers at the Texas Children’s Hematology Center will host an awareness event Sept. 28 for sickle cell patients ages 8 to 12 and their parents, where they will present the latest in treatment and research and offer fun activities for the kids, including games and videos focused on life coping skills, dealing with pain and the implications of the disease on the child’s education, among other topics.
Baylor College of Medicine