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JAMA. 2003 Apr 2;289(13):1645-51.

Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment.

Author information

Boston University School of Medicine, Center of Excellence in Sickle Cell Disease, Boston Medical Center, Boston, Mass 02118, USA.

Erratum in

  • JAMA. 2003 Aug 13;290(6):756.



Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality.


To determine whether hydroxyurea attenuates mortality in patients with SCA.


Long-term observational follow-up study of mortality in patients with SCA who originally participated in the randomized, double-blind, placebo-controlled Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), conducted in 1992-1995, to determine if hydroxyurea reduces vaso-occlusive events. In the MSH Patients' Follow-up, conducted in 1996-2001, patients could continue, stop, or start hydroxyurea. Data were collected during the trial and in the follow-up period.


Inpatients and outpatients in 21 sickle cell referral centers in the United States and Canada.


Two-hundred ninety-nine adult patients with frequent painful episodes enrolled in the follow-up. Follow-up data through May 2001 were complete for 233 patients.


In the MSH, patients were randomly assigned to receive hydroxyurea (n = 152) or placebo (n = 147).


Mortality, HbF levels, painful episodes, acute chest syndrome, and blood cell counts. The randomized trial was not designed to detect specified differences in mortality.


Seventy-five of the original 299 patients died, 28% from pulmonary disease. Patients with reticulocyte counts less than 250 000/mm3 and hemoglobin levels lower than 9 g/dL had increased mortality (P =.002). Cumulative mortality at 9 years was 28% when HbF levels were lower than 0.5 g/dL after the trial was completed compared with 15% when HbF levels were 0.5 g/dL or higher (P =.03 ). Individuals who had acute chest syndrome during the trial had 32% mortality compared with 18% of individuals without acute chest syndrome (P =.02). Patients with 3 or more painful episodes per year during the trial had 27% mortality compared with 17% of patients with less frequent episodes (P =.06). Taking hydroxyurea was associated with a 40% reduction in mortality (P =.04) in this observational follow-up with self-selected treatment. There were 3 cases of cancer, 1 fatal.


Adult patients taking hydroxyurea for frequent painful sickle cell episodes appear to have reduced mortality after 9 of years follow-up. Survival was related to HbF levels and frequency of vaso-occlusive events. Whether indications for hydroxyurea treatment should be expanded is unknown.

[Indexed for MEDLINE]

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