Study Finds Sickle Cell Drug Safe and Effective for Infants and Toddlers

The findings from one of the largest sickle cell anemia studies of its kind could change the standard of care for very young children with the disease. Researchers from the Miller School, and 13 medical centers across the United States, conducted a randomized double-blinded trial to test the impact of hydroxyurea therapy for children between the ages of nine to eighteen months. The results of the two year NIH-funded clinical trial will be published in the May 14 issue of the prestigious British medical journal Lancet.

The objective of the trial was to determine if hydroxyurea therapy is effective in preventing organ dysfunction and clinical complications. The investigators at the BABY HUG (Pediatric Hydroxyurea Phase III Clinical Trial) clinical centers enrolled almost 200 patients and 86-percent completed the study. Half of the patients received hydroxyurea and half received placebo.

“This study represents a major step forward in treatment of the often devastating symptoms of sickle cell anemia in the infant or toddler- pain, painful swelling of the hands and feet, and a strong, but not statistically significant reduction of hospitalization, acute chest syndrome, and need for transfusion”, said Daniel Armstrong, Ph.D., professor and associate chair of pediatrics and director of the University of Miami Sickle Cell Center. “Before hydroxyurea, the only treatment options were blood transfusions every 3-4 weeks, bone marrow transplantation, or acute management of symptoms, often involving repeated hospitalization. Hydroxyurea clearly offers these young children a chance to live a relatively normal life outside the hospital, and represents one of the first major breakthroughs in care in decades.”

Sickle cell anemia is a disease passed through families in which there aren’t enough healthy red blood cells to carry oxygen through your body. Normally red blood cells are flexible and round, and move easily through your blood vessels. In sickle cell disease, high levels of sickle hemoglobin cause the cells collapse. The resulting cells are shaped like sickles or crescent moons and due to their shape they often get stuck in the small blood vessels blocking blood flow to most of the organs in the body. This can cause many severe and life-threatening problems, including severe pain, damage to the kidneys, liver, and spleen, acute chest syndrome, or stroke.

Hydroxyurea is used to reduce the rate of these painful attacks by increasing the production of fetal hemoglobin, which helps prevent the sickling process. Sold under the brand names Hydrea and Droxia, hydroxyurea is an anti-cancer drug first used in myeloproliferative disorders, including chronic myelocytic leukemia, polycythemia vera and essential thrombocythemia, all blood disorders.

Fifteen years ago a study of hydroxyurea in adults demonstrated that the medication reduced episodes of pain and acute chest syndrome, hospitalizations and transfusions in adults with sickle cell disease. Subsequent multiple smaller studies have shown similar benefits and minimal toxicity in school-age children and adolescents.

In 1999, the U.S. National Heart, Lung and Blood Institute began the research with a pilot trial (HUSOFT) which showed that very young children tolerated a liquid hydroxyurea formulation; they then moved on to the Phase III BABY HUG trial.

Dr. Armstrong and Julio Barredo, M.D., director of the Division of Pediatric Hematology/Oncology at the University of Miami then at the Medical University of South Carolina and also a co-author on the Lancet publication, were part of the original study design and steering committee for the BABY HUG study. Ofelia Alvarez, M.D., the pediatric clinical director at the University of Miami, was the local principal investigator for BABY HUG at the University of Miami and also a member of the study steering committee. Tally Hustace, a pediatric sickle cell nurse coordinator, also played an essential role in supporting families who participated in this very time-demanding and complex study.

The University of Miami has been a leader in research on sickle cell disease in the United States for more than 35 years. One of the original Comprehensive Sickle Cell Centers in 1975, the University of Miami Sickle Cell Center is one of only eleven Basic and Translational Research Programs in Sickle Cell Disease awarded by the National Heart, Lung, and Blood Institute. Investigators at the University of Miami have played a leadership role in every major natural history study and multi-center clinical trial on sickle cell disease funded by the NIH since the mid-1980s,

We could not have made these advances without an incredible partnership with our patients and their families”, Dr. Armstrong is quick to remind. “We have some of the most willing and dedicated patients in the world. Their selfless devotion to help find a cure for everyone is the major reason that these studies have taken place and resulted in improved care for all children, adolescents, and adults with this awful disease.”