Conference Coverage

New Data Support Continuing Hydroxyurea for Pediatric Sickle Cell


 

FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY

SAN DIEGO – Mounting data from a federally funded follow-up to the BABY HUG study continue to demonstrate that hydroxyurea is a safe and effective treatment for young children with sickle cell anemia.

The results confirm findings published earlier this year from the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG), a randomized, placebo-controlled study sponsored by the National Institutes of Health and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

BABY HUG showed that hydroxyurea administered to 9- to 18-month-old children with sickle cell anemia provides significant clinical benefits, including a decrease in pain crises, acute chest syndrome events, and need for transfusion and hospital admission (Lancet 2011; 377:1663-72).

Hydroxyurea is approved to prevent sickle cell complications in adults with sickle cell anemia, but it is not currently indicated for use in children. Dr. Zora R. Rogers discussed the new data during a press briefing prior to a presentation at the annual meeting of the American Society of Hematology.

"We need to complete the data analysis and to critically examine the growth and development of this population with respect to hydroxyurea use," lead author Dr. Rogers said of the follow-up study, which terminates on Dec. 31, 2011. "But on a macroscopic level there [do] not appear to be any differences observed."

In 2008 Dr. Rogers, professor of pediatrics at the University of Texas Southwestern Medical Center, Dallas, and her associates at 14 centers launched the BABY HUG Follow-Up Study I to assess the safety and efficacy of continued treatment with hydroxyurea in infants with sickle cell anemia. The population consisted of 163 children aged 28-44 months who had participated in the original BABY HUG trial and who had completed at least 18 months of randomized treatment of either hydroxyurea or placebo. The researchers collected clinical and laboratory data every 6 months from patient medical records, including use and dosage of hydroxyurea, blood counts, clinical imaging, and frequency of sickle cell-related complications.

Of the 163 families that enrolled children in the follow-up study, 133 (82%) chose open-label hydroxyurea at the beginning of follow-up and every 6 months 65%-75% of the families reported that their children continued to take the drug. No patient developed intolerance or stopped permanently because of toxicity.

Dr. Rogers, clinical director of the bone marrow failure and general hematology program at Children’s Medical Center, Dallas, presented preliminary analyses as of Oct. 18, 2011, that amounted to 497 patient-years of follow-up. Compared with children who are not taking hydroxyurea, those who continue to take hydroxyurea have statistically lower rates of pain crises requiring emergency department visits (a rate of 29 vs. 54 per 100 patient-years, respectively), episodic transfusions (18 vs. 34 per 100 patient-years), and hospital admissions for any reason (73 vs. 132 per 100 patient-years), including acute chest syndrome or febrile illness.

In their abstract, the researchers pointed out that the decrease in acute chest syndrome episodes "is similar to the effect demonstrated with hydroxyurea use in the randomized BABY HUG trial in younger infants and consistent with published trials detailing the benefit of hydroxyurea therapy in older children and adults. The decrease in the rate of admission for febrile events in hydroxyurea-treated patients is also comparable to that in the randomized trial, but the reason for this benefit is uncertain."

There were no differences between the two groups in hospitalization rates for painful events, including dactylitis. Two patients in the non-hydroxyurea group each had a stroke. There were also no differences between the two groups in the frequency of a palpable spleen or rate of acute splenic sequestration crises. Through 36 months of follow up, children taking hydroxyurea had persistently higher hemoglobin and mean corpuscular volume and lower white blood cell count and absolute neutrophil count, compared with those not taking the drug.

Dr. Susan B. Shurin, acting director of the National Heart, Lung, and Blood Institute (NHLBI), characterized the findings as important in efforts to get an early handle on the burden of disease associated with sickle cell anemia.

"The internists who inherit the patients who have gone through pediatric practitioners have a powerful sense that they reach adolescence doing pretty well, and then things kind of fall apart," Dr. Shurin said. "The clear evidence that prevention of organ damage and prevention of complications of sickle cell anemia would be much preferable to trying to manage once they develop has been the motivation" for this work.

The BABY HUG investigators "believe that ongoing follow-up of this cohort is essential to continue to define the potential benefits as the children grow and to observe for late toxicity," Dr. Rogers said. "We are in final discussions with the NHLBI for an additional contract in support of 5 more years of follow-up."

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