NIH-funded study finds sickle cell treatment safe for young children
A drug now used to treat adults who have sickle cell disease appears to be safe for children aged 8 to 19 months, results from a new National Institutes of Health-funded study suggest. The drug, hydroxyurea, reduced pain episodes and improved key blood measurements in the children studied, according to researchers.
"There are now strong reasons for health care professionals to consider starting children who have sickle cell disease as early as possible on hydroxyurea," said Susan B. Shurin, M.D., acting director of the National Heart, Lung, and Blood Institute (NHLBI) of the NIH, which supported the study. "Less pain and fewer hospital stays are obvious improvements in the quality of life for the youngest children born with this condition."
Results of the study, The Pediatric Hydroxyurea Phase III Clinical Trial, known as Baby HUG, will appear May 14 in the Lancet. The multicenter study was led by investigators at St. Jude Children's Research Hospital, in Memphis, Tenn.
The study was designed to determine whether hydroxyurea could protect spleen and kidney function in very young children who have sickle cell disease. Loss of spleen function is associated with increased risks of serious bacterial infections. The study also sought to determine whether hydroxyurea treatment would reduce the frequency of other complications, including pain events and hospital stays.
Baby HUG enrolled 193 children, making it the largest trial to test hydroxyurea treatment in very young patients. Researchers randomly assigned 96 participants to a group taking hydroxyurea and 97 participants to a control group taking a placebo, an inactive substance.
"Families who enrolled their children in this important study are heroes for helping us find better treatments that will benefit children now and in the future," said Jonathan Goldsmith, M.D., an NHLBI program officer and a study author.
Children who were given hydroxyurea fared about the same as those children not given the drug based on scans of the spleen and examination of the kidney's filtering capacity, the main tests used to evaluate the treatment. However, the children given hydroxyurea showed improvements in other tests of spleen and kidney function. Hydroxyurea also was shown to decrease the occurrences of pain episodes. Those in the hydroxyurea group experienced half as many pain events, 177 events spread among 62 participants, versus 375 events spread among 75 participants in the placebo group.
The treatment lowered the risk of dactylitis, which is pain in the hands and feet often accompanied by swelling. Children treated with hydroxyurea also experienced fewer episodes of acute chest syndrome (eight instances, compared with 17 in the placebo group), needed fewer hospitalizations (232, compared to 324 in the placebo group), and needed fewer blood transfusions, which are sometimes given to increase red blood cell counts. Acute chest syndrome is a pneumonia-like infection that can be life-threatening.
Sickle cell disease is an inherited blood disorder that affects approximately 100,000 Americans. It is most prevalent in persons of African, Hispanic, Mediterranean, and Middle Eastern descent.
People living with this disease have two copies of an altered gene responsible for producing hemoglobin, the protein in red blood cells that transports oxygen throughout the body. Those with sickle cell disease produce hemoglobin that changes shape and becomes stiff after releasing its oxygen. The transformation, which can cause normally round and flexible red blood cells to become misshapen and sticky, slows the flow of blood to the tissues. These changes contribute to fatigue and pain, which are among the hallmarks of this disease. There is no widely available cure for sickle cell disease, though bone marrow transplants have cured some younger patients. Those who live with the disease have life-long anemia due to the rapid destruction of red blood cells in the body. Some people with sickle cell disease undergo periodic blood transfusions to increase the number of healthy red blood cells.
Hydroxyurea was originally developed as a cancer treatment, but has been successful in reducing episodes of severe pain, known as pain crises, in adults with sickle cell disease. The drug is intended to raise levels of fetal hemoglobin, a form of hemoglobin everyone produces before birth and during the first few months of life. As time goes on, this fetal hemoglobin almost disappears from a person's system as production of adult hemoglobin takes over. Increasing fetal hemoglobin levels for people who have sickle cell disease is helpful because fetal hemoglobin reduces the tendency of sickle hemoglobin to change the shape of the red blood cells.
As in adults, the children taking hydroxyurea in Baby HUG showed elevated levels of fetal hemoglobin compared to the children receiving a placebo.
While results of the primary spleen and kidney function tests did not differ in the two groups, it is possible that improvements may arise in future years. Researchers plan to follow study participants through 2016, when the children will be between 9 and 13 years of age, to look at the long-term effects of the treatment. The extended study will test brain, heart, kidney, lung, and spleen function; examine growth as well as psychological and social development; and provide information about the predictive value of blood tests.
"Hydroxyurea offers an excellent treatment option to improve the lives of infants and potentially all persons with sickle cell anemia,"said Winfred C. Wang, M.D., principal investigator of Baby HUG, of the St. Jude Children's Research Hospital.
To arrange an interview with an NHLBI spokesperson, please contact the NHLBI Communications Office at (301) 496-4236. To arrange an interview with Dr. Wang, please contact the St. Jude Children's Research Hospital Public Relations Office at (901) 595-3061.
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at www.nhlbi.nih.gov.