In a study spanning 20 years, the 10-year probability of survival was 91% for patients treated with daily hydroxyurea, compared with 70% for those getting conventional treatment, according to Ersi Voskaridou, M.D., of Laikon General Hospital in Athens, Greece.
The drug is the main pharmacological agent used to prevent painful sickle cell crises and, as expected, it also reduced morbidity, Dr. Voskaridou reported at the American Society of Hematology meeting here.
The surprise in the findings came from the fact that -- owing to the study design -- those getting hydroxyurea were among the sickest, with more than three crises a year and other complications including stroke, acute chest syndrome, and hemolysis.
"Patients with severe sickle cell syndrome were included," said co-author Evangelos Terpos, M.D., of the General Air Force Hospital in Athens. "That's why we were so surprised by the benefit."
The finding comes in the context of an NIH consensus statement earlier this year that said the drug was under-used in the U.S. for prevention of the morbidity associated with sickle cell disease.
The researchers presented data on 330 patients who were prospectively followed, starting in 1991, with a median follow-up for the hydroxyurea group of eight years and five years for the conventional treatment group.
All told, 131 patients got daily hydroxyurea at 20 milligrams per kilogram of body weight, although some patients had the dose modified because of toxicity or lack of effectiveness, Dr. Voskaridou said.
Over the course of the study there were 12 deaths in the hydroxyurea group, compared with 47 in the conventional treatment group, or 9.1% versus 23.6% -- a difference that was significant at P=0.001.
The researchers also found:
- The frequency of severe crises fell among those getting the drug, from an average of 7.4 crises a year to 0.2, which was significant at P<0.001.
- Hospital admissions were significantly reduced (P<0.001), from 2.1 a year on average to 0.06.
- Chest syndrome frequency fell from 6.1% to 0.8%, significant at P=0.0013.
There were no changes in the frequency of avascular necrosis or cerebrovascular episodes, Dr. Voskaridou said.
Side effects of hydroxyurea were predictable, minimal, and easily managed, she said.
Although the study is not a gold-standard randomized trial, the findings may understate the value of the drug, according to Nancy Berliner, M.D., of Brigham and Women's Hospital in Boston, who co-moderated the press conference at which Dr. Voskaridou presented her research.
"If you were to do a randomized trial, (the study) suggests that, if anything, it would under-estimate the effect of hydroxyurea," Dr. Berliner, president-elect of ASH, said, "because they had markedly improved survival compared with people who appeared to have milder disease."
The study adds support to the idea that the drug improves mortality, said Michael DeBaun, M.D., of St. Louis Children's Hospital, co-moderator of the press conference.
He said a longitudinal observational study, a follow-up to the original study that established the drug as a way to reduce morbidity, had also suggested "as a secondary analysis" that there might be a survival benefit.
"So now we have, in the adult population, two separate studies that are improving the level of evidence that hydroxyurea is effective at prolonging life," he said.
|Dr. Voskaridou did not report outside support for the study or any conflicts.
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine